**4. Vegetable proteins and their quality**

**Figure 4** shows a wide range of vegetable-based proteins derived from several sources. These can be extracted from low-cost and ecological sources such as agricultural wastes and crop and oil industry by-products, which can help to achieve food security [16].

Because of the varied metabolic requirements of certain tissues, rats, and humans have varying amino acid requirements. The fact that the protein-energy ratio of animal proteins (or a combination of proteins) does not reach its maximum value but rises when methionine is added supports the notion that rodents have a higher sulfur amino acid need than humans. The consumption of a protein in people can be measured by monitoring the fecal matter and urine nitrogen (N) losses; it is predicated on the nitrate adjustment study premise. These studies indicated that some vegetable proteins, particularly beans and wheat, are underappreciated. Wheat's net protein utilization was calculated to be 41% when compared to egg protein. In humans, data show that most vegetable sources of protein have true digestibility in the 80–90% range, with references having lower digestibility (e.g., "rice, cereal": 75% and "rice, polished": 88%) and others having higher digestibility (e.g., "wheat, refined": 96%, "soy protein isolate": 95%). When protein percentage is purer, vegetable protein is much more digestive. Instead of looking at total nitrogen levels, per specific amino acid's digestion should be studied, as this has been suggested for many years. Because some protein acids personal digestion fluctuates or is lower than that of others for several reasons, average digestion is an insufficient proxy with each protein bioavailability.

The digestibility of various dietary proteins was found to be between 89 and 95 % in investigations using advanced techniques. The findings were 89 %–92 % for soy protein isolate, pea protein flour or isolate, wheat flour, and lupine flour, which were close to those reported for eggs (91%) and meat (90 –94 %), but somewhat lower than those published for milk protein isolate (95 %). When absorbed at a level that fulfills the entire protein needs (e.g., 0.66 g/kg weight), a dietary protein with an amino acid score offers precisely the exact quantities of proteins that satisfy metabolic requirements and at a ratio in which no amino acid limits utilization of others. Lysine in grains and sulfur amino acids in beans typically emerge as restricted AAS stands for Amino acid score of vegetable protein. A closer analysis of the literature discloses that lysine rates are reduced or near zero in cereals such as sorghum,

**Figure 4.** *Major plant-based protein sources.*

wheat, triticale (47, 49, and 62%), and rice (80%), and also low in few more both these sources (walnuts and almonds: 60%). In contrast, it is high or extremely high in other sources, notably legumes (e.g., pea: 168 %; fava bean: 152 %; soybean: 134 %) and animal proteins (milk: 168 %; beef: 193 %; egg: 160 %) [18].


3.1. Drawbacks of the conventional commercial pulping technique

The conventional commercial pulping procedures of annual plants include both kraft and soda pulping. The major drawback of these pulping protocols is that in the case of alkaline cooking liquors, apart from the delignification process, significant decomposition of carbohydrates portion of the lignocellulose biomass is observed by peeling-off reactions and alkaline hydrolysis. Optimum alkaline cooking condition is pertinent as excess alkaline loading could result in lowering of the ISO brightness due to the concept of alkaline darkening. Furthermore, sodium hydroxide easily dissolves phenolic lignin structures; besides, lignin undergoes condensation reactions under strong alkaline conditions which reduce the reactivity of residual lignin. In the like manner, strong alkaline cooking liquors dissolve high silica content of annual plants and precipitates evaporation problems in soda recovery boilers and in the causticizing plant [34].

In contrast, conventional kraft pulping has been used commercially for paper packaging from annual plants such as wood and some bamboo species, due to good paper properties. Kraft pulping has been found suitable for all ranges of fiber sources. It gives paper of high tensile strength and also high efficiency of the recovery of cooking chemicals [35]. In non-phenolic lignin moieties only β-ethers are cleaved. This has also an impact on bleaching. Among the disadvantages of kraft pulping process, low yield pulp, high consumption of bleaching chemicals, emission of obnoxious odor from the pulping process and large mill size require a tremendous capital investment.

Compared to soda pulps, soda/anthraquinone (soda/AQ) pulps have slightly better bleaching ability, higher yield and sometimes better strength. Similarly, alkali sulfite pulping had been known to give good strength properties and significantly higher yields than kraft process [36]. The addition of anthraquinone helped to reduce Kappa number from the unbleached pulp.

In order to overcome the abovementioned challenges, Patt and Kordsachia [37] discovered that the addition of methanol or ethanol extended delignification to levels below kraft or sulfite pulps. They named their process as alkali-sulfite-anthraquinone methanol (ASAM). Unlike the conventional pulping protocols, ASAM pulping process has dual advantages of paper properties and higher pulp brightness. In addition, ASAM pulping results in pulp with high pulp yield, low Kappa number and high paper strength. Furthermore, the obnoxious odor from methyl mercaptan that is generated during kraft pulping is completely absent in ASAM pulping.

#### 3.2. Mechanism of alkaline sulfite anthraquinone and methanol (ASAM)

Alkaline sulfite anthraquinone with methanol pulping known as the ASAM process was developed by Patt and Kordsachia in 1986 as an alternative cooking process option for soda and kraft pulping processes. According to the authors, the chemical materials that make up the ASAM process are sodium sulfite (Na2SO3), sodium hydroxide (NaOH), anthraquinone (AQ) and methanol (CH3OH). These materials play a unique role in the pulping milieu because, sodium sulfite and sodium hydroxide are the major ingredients of the alkaline sulfite process while the anthraquinone and methanol act as catalysts to enhance the chemical penetration delignification of the lignocellulose biomass. Table 3 shows the characteristics of cooking parameters in the ASAM pulping process, while Table 4 gives a summary of the key role of each chemical constituent in ASAM blend.

The mechanism of ASAM pulping process can be viewed with respect to the cooking parameters.


**2.1 Amelogenesis and developmental defects of enamel**

Tooth development is strictly genetically controlled but sensitive to environmental disturbances (Suckling et al., 1988) since teeth have been formed they do not undergo remodeling. (Brook, 2009) During dental development, a single layer of inner enamel epithelial cells undergoes a remarkable change in cell shape in preparation for the secretion of enamel extracellular matrix. These cells develop into tall ameloblasts with cellular extensions called Tomes' processes, which function during enamel matrix secretion. Following generation of the enamel layer, the ameloblasts shorten and reorganize during the transition stage; they then enter maturation, where they change histologically from ruffle-ended to smooth-ended at the location where Tomes' processes have retracted. These cells reduce the enamel protein content and increase the mineral content so that the enamel layer can develop into the hardest tissue in the body. Finally, the cells shorten further and adhere to the enamel surface until just before eruption of the tooth into the oral cavity (Smith , 1979). In other words, enamel formation occurs in three stages:

The mineralization of the enamel matrix is described as a two-step process. Firstly, the ameloblasts secrete an organic matrix that is immediately mineralized to about 30% by weight. Secondly, when the full thickness of enamel has been secreted by an ameloblast, a progressive increases in mineral content begin. Smooth-ended ameloblasts remove of water and proteins from the enamel matrix, whereas ruffle-ended ameloblasts participate in the active transport of calcium and phosphate into the matrix. The principal proteins acted in the enamel matrix are:

According to BROOK, 2009 (Brook, 2009) in the secretory stage the enamel protein matrix deposited by the ameloblasts is predominantly formed of amelogenin (85%). At the midsecretory stage for appositional crystal growth and structural maintenance amelogenin is essential. However, while enamelin contributes less than 5% of the matrix it plays a major role in controlling the initiation of hydroxyapatite formation in early amelogenesis, being necessary for creating and maintaining enamel crystallite elongation at the mineralization front immediately adjacent to ameloblasts. The further enamel protein ameloblastin is a celladhesion molecule that maintains the differentiation stage of secreting ameloblasts and

Molar Incisor Hypomineralization:

(Jalevik et al., 2005)

increase in C content. (Fearne et al., 2004)

Morphological, Aetiological, Epidemiological and Clinical Considerations 429

no evidence of defective structure. At a more occlusal level, the defect is confined to the inner enamel while the outer enamel does not appear to be affected. As move occlusally, the hypomineralisation becomes more evident, eventually spreading to span the entire thickness of the enamel. The defects usually did not involve the cusp tips; but if a marginal

Microstructural analysis of sound and hypomineralised enamel showed two marked changes in microstructure in the MIH affected enamel region; less dense prism structure with loosely packed apatite crystals and wider sheath regions. (Xie et al., 2008) These changes appear to occur during enamel maturation and may be responsible for the marked reduction in hardness and elastic modulus of the affected enamel. (Fagrell et al., 2010) In addition, the enamel in the transitional region adjacent to the demarcated defects in MIH has also notable alterations in their prism sheaths. Despite the translucent, normal appearance, the transitional region between the affected and unaffected regions in MIH teeth had weakened prism sheaths which compromised its overall mechanical properties. (Chan et al., 2010) The reason for this is unclear but may be also related to the lack of organization of the enamel crystals due poorly demarcated prism boundaries in the affected regions (Mahoney et al., 2004) and the packing of the crystals seemed to be less tight and less well organized in the porous parts. The borders of the enamel rods were indistinct and the interrods zones hardly visible, or the rods were very thin with wide interrod zones.

Semi-quantitative analysis by energy dispersive X-ray spectrometry in extracted MIH affected teeth showed that the mineral composition of this type of enamel is low (Javelik & Norén, 2001), on average the mineral density is about 19 % lower than sound enamel (Baroni & Marchionni, 2011, Farah et al., 2010a, Jalevik & Noren, 2000, Schulze et al., 2004), there is a decrease in Ca:P ratio in the enamel (Rodd et al., 2007a, Jalevik, 2001) related to an

Also, MIH enamel has substantially higher protein content than normal enamel, but a nearnormal level of residual amelogenins. This characteristic distinguishes MIH from hypomaturation defects that contain high residual amelogenins such as *Amelogenesis Imperfecta* or Fluorosis (Mangum et al., 2010a, Wright et al., 1996, Wright et al., 1997) and in turn typifies MIH as a hypocalcification defect as mentioned above. Pathogenically, it points to a pre-eruptive disturbance of mineralization involving albumin probably due to an overabundance of albumin that interferes with the mineralisation process. It justifies the porosities exhibited in the subsurface (Jalevik & Noren, 2000) because albumin degradation may be a prerequisite for maximal crystal growth in the maturation stage of enamel. (Farah et al., 2010b, Farah et al., 2010c, Mangum et al., 2010b) The presence of excessive albumin seemed to be promote KLK4 inactivity resulting in enamel with elevated protein content and reduced mineral content. In cases of MIH with post-eruptive breakdown, on the exposed surface there is a subsequent protein adsorption on the exposed hydroxyapatite matrix. An indicator of the severity of MIH affected teeth is the actual organic content of its enamel (Farah et al., 2010a) Brown enamel, the most severe MIH lesion, has the highest protein content (15–21-fold greater), whilst the protein content of white/opaque and yellow enamel are both markedly higher (8-fold greater) than sound enamel. (Farah et al., 2010a) For sound enamel, when subjected to mechanical forces the controlling deformation mechanism was distributed shearing within nanometer thick protein layer between its

ridge was involved, its maximum height was affected. (Farah et al., 2010a)

controls their secretion. The subsequent breakdown and removal of matrix proteins by means of proteolytic processing is essential for further development and mineralisation. Enamelysin (Mmp20), a matrix metalloproteinase, and the enamel serine protease kallikrein 4 (Klk4) are two major molecules involved in this process. (Wright et al., 2009, Bartlett et al., 2011) Mmp20 is expressed in secretory stage ameloblasts and also has effects on them maturation stage as well as on the mineralisation of mantle dentine. Klk4, present in both ameloblasts and odontoblasts, is expressed at the enamel transition and maturation phase. KLK4 which is secreted into the enamel by ameloblasts during the transition and maturation stages of amelogenesis. Klk4 degrades the organic matrix remaining from the secretion stage. This facilitates the continued deposition of minerals into enamel required for full mineralisation of hard enamel. Amelogenin is cleaved by Mmp20 and later degraded during maturation by Klk4. Within the ameloblasts Dlx3 and Dlx6 are expressed throughout the presecretory, secretory and maturation stages. During secretion Dlx2 is switched off and Dlx1 expression is upregulated. The Dlx homeobox genes may influence enamel formation by the regulation of amelogenin expression. Normal enamel thickness may be achieved by Runx2 suppressing enamel protein expression at the end of the secretory stage to give normal enamel thickness. In the maturation phase Runx2 induces Klk4 and upregulates basal membrane protein expression to induce ameloblast attachment to the enamel matrix. (Brook, 2009, Wrightet al., 2009, Bartlett et al., 2011)

In general, systemic factors that disturb the ameloblasts during the secretory stage cause restrictions of crystal elongation and result in pathologically thin, or hypoplastic enamel. On the other hand, disturbances during the transitional and/or maturation stage of amelogenesis result in pathologically soft (hypomaturated, hypomineralised) enamel of normal thicknesses. (Suga, 1989) According to REID AND DEAN, 2006 (Reid & Dean, 2006), enamel formation as a whole takes approximately one thousand days. Two thirds of this time is devoted to the maturation stage of amelogenesis. Considering this, the most critical period for enamel defects of first permanent molars and incisors is the first year of life coinciding with their early maturation (Alaluusua, 2010). In this period ameloblasts are highly sensitive to environmental disturbances. (Suckling, 1989) Hypomineralisation may also develop later because enamel maturation in the first permanent molars takes several years (later maturation stage). (Alaluusua, 2010)

### **2.2 Amelogenesis and MIH**

As mentioned previously, there are no hypoplastic defects in MIH affected teeth because there is not any discernable reduction in enamel thickness teeth. (Farah et al., 2010a, Fearne et al., 2004) It suggests that any reduction in enamel thickness seen clinically is indicative of post-eruption disintegration of enamel. Furthermore, this clarify that whatever insult affects the developing tooth it happens after the enamel secretion is completed and affects the maturation phase of the mineralization process in a localized area of enamel. (Farah et al., 2010a)

#### **2.3 Characteristics of MIH affected teeth**

MIH is a qualitative defective enamel classified as hypomineralised type that follows the natural incremental lines of enamel formation, from cuspal to cement-enamel junction. (Farah et al., 2010a, Fearne et al., 1994) In the most cervical section, the enamel is sound with

controls their secretion. The subsequent breakdown and removal of matrix proteins by means of proteolytic processing is essential for further development and mineralisation. Enamelysin (Mmp20), a matrix metalloproteinase, and the enamel serine protease kallikrein 4 (Klk4) are two major molecules involved in this process. (Wright et al., 2009, Bartlett et al., 2011) Mmp20 is expressed in secretory stage ameloblasts and also has effects on them maturation stage as well as on the mineralisation of mantle dentine. Klk4, present in both ameloblasts and odontoblasts, is expressed at the enamel transition and maturation phase. KLK4 which is secreted into the enamel by ameloblasts during the transition and maturation stages of amelogenesis. Klk4 degrades the organic matrix remaining from the secretion stage. This facilitates the continued deposition of minerals into enamel required for full mineralisation of hard enamel. Amelogenin is cleaved by Mmp20 and later degraded during maturation by Klk4. Within the ameloblasts Dlx3 and Dlx6 are expressed throughout the presecretory, secretory and maturation stages. During secretion Dlx2 is switched off and Dlx1 expression is upregulated. The Dlx homeobox genes may influence enamel formation by the regulation of amelogenin expression. Normal enamel thickness may be achieved by Runx2 suppressing enamel protein expression at the end of the secretory stage to give normal enamel thickness. In the maturation phase Runx2 induces Klk4 and upregulates basal membrane protein expression to induce ameloblast attachment to the enamel matrix.

In general, systemic factors that disturb the ameloblasts during the secretory stage cause restrictions of crystal elongation and result in pathologically thin, or hypoplastic enamel. On the other hand, disturbances during the transitional and/or maturation stage of amelogenesis result in pathologically soft (hypomaturated, hypomineralised) enamel of normal thicknesses. (Suga, 1989) According to REID AND DEAN, 2006 (Reid & Dean, 2006), enamel formation as a whole takes approximately one thousand days. Two thirds of this time is devoted to the maturation stage of amelogenesis. Considering this, the most critical period for enamel defects of first permanent molars and incisors is the first year of life coinciding with their early maturation (Alaluusua, 2010). In this period ameloblasts are highly sensitive to environmental disturbances. (Suckling, 1989) Hypomineralisation may also develop later because enamel maturation in the first permanent molars takes several

As mentioned previously, there are no hypoplastic defects in MIH affected teeth because there is not any discernable reduction in enamel thickness teeth. (Farah et al., 2010a, Fearne et al., 2004) It suggests that any reduction in enamel thickness seen clinically is indicative of post-eruption disintegration of enamel. Furthermore, this clarify that whatever insult affects the developing tooth it happens after the enamel secretion is completed and affects the maturation phase of the mineralization process in a localized area of enamel. (Farah et al.,

MIH is a qualitative defective enamel classified as hypomineralised type that follows the natural incremental lines of enamel formation, from cuspal to cement-enamel junction. (Farah et al., 2010a, Fearne et al., 1994) In the most cervical section, the enamel is sound with

(Brook, 2009, Wrightet al., 2009, Bartlett et al., 2011)

years (later maturation stage). (Alaluusua, 2010)

**2.3 Characteristics of MIH affected teeth**

**2.2 Amelogenesis and MIH**

2010a)

no evidence of defective structure. At a more occlusal level, the defect is confined to the inner enamel while the outer enamel does not appear to be affected. As move occlusally, the hypomineralisation becomes more evident, eventually spreading to span the entire thickness of the enamel. The defects usually did not involve the cusp tips; but if a marginal ridge was involved, its maximum height was affected. (Farah et al., 2010a)

Microstructural analysis of sound and hypomineralised enamel showed two marked changes in microstructure in the MIH affected enamel region; less dense prism structure with loosely packed apatite crystals and wider sheath regions. (Xie et al., 2008) These changes appear to occur during enamel maturation and may be responsible for the marked reduction in hardness and elastic modulus of the affected enamel. (Fagrell et al., 2010) In addition, the enamel in the transitional region adjacent to the demarcated defects in MIH has also notable alterations in their prism sheaths. Despite the translucent, normal appearance, the transitional region between the affected and unaffected regions in MIH teeth had weakened prism sheaths which compromised its overall mechanical properties. (Chan et al., 2010) The reason for this is unclear but may be also related to the lack of organization of the enamel crystals due poorly demarcated prism boundaries in the affected regions (Mahoney et al., 2004) and the packing of the crystals seemed to be less tight and less well organized in the porous parts. The borders of the enamel rods were indistinct and the interrods zones hardly visible, or the rods were very thin with wide interrod zones. (Jalevik et al., 2005)

Semi-quantitative analysis by energy dispersive X-ray spectrometry in extracted MIH affected teeth showed that the mineral composition of this type of enamel is low (Javelik & Norén, 2001), on average the mineral density is about 19 % lower than sound enamel (Baroni & Marchionni, 2011, Farah et al., 2010a, Jalevik & Noren, 2000, Schulze et al., 2004), there is a decrease in Ca:P ratio in the enamel (Rodd et al., 2007a, Jalevik, 2001) related to an increase in C content. (Fearne et al., 2004)

Also, MIH enamel has substantially higher protein content than normal enamel, but a nearnormal level of residual amelogenins. This characteristic distinguishes MIH from hypomaturation defects that contain high residual amelogenins such as *Amelogenesis Imperfecta* or Fluorosis (Mangum et al., 2010a, Wright et al., 1996, Wright et al., 1997) and in turn typifies MIH as a hypocalcification defect as mentioned above. Pathogenically, it points to a pre-eruptive disturbance of mineralization involving albumin probably due to an overabundance of albumin that interferes with the mineralisation process. It justifies the porosities exhibited in the subsurface (Jalevik & Noren, 2000) because albumin degradation may be a prerequisite for maximal crystal growth in the maturation stage of enamel. (Farah et al., 2010b, Farah et al., 2010c, Mangum et al., 2010b) The presence of excessive albumin seemed to be promote KLK4 inactivity resulting in enamel with elevated protein content and reduced mineral content. In cases of MIH with post-eruptive breakdown, on the exposed surface there is a subsequent protein adsorption on the exposed hydroxyapatite matrix. An indicator of the severity of MIH affected teeth is the actual organic content of its enamel (Farah et al., 2010a) Brown enamel, the most severe MIH lesion, has the highest protein content (15–21-fold greater), whilst the protein content of white/opaque and yellow enamel are both markedly higher (8-fold greater) than sound enamel. (Farah et al., 2010a) For sound enamel, when subjected to mechanical forces the controlling deformation mechanism was distributed shearing within nanometer thick protein layer between its

Molar Incisor Hypomineralization:

Fig. 3. Multifactorial aetiology of MIH

Morphological, Aetiological, Epidemiological and Clinical Considerations 431

period, socioeconomic factors and nutrition during first 3 years of child life were entered into databank. Besides, in this study, randomly, there were two-age and sex-matched children to each MIH child. After a regression logistic analyses, the results showed a positive association between severe demarcated opacities in permanent first molars with breastfeeding for more than 6 months, late introduction of gruel and late introduction of infant formula. Moreover, a combination of these variables increased the risk to develop severe demarcated opacities by more five times. According these results, the authors concluded that nutritional conditions during first 6 months of life may influence the risk to

develop severe demarcated opacities in first permanent molars. (Fagrell et al., 2011)

constituent mineral crystals; whereas for hypomineralised enamel micro cracking and subsequent crack growth were more evident in its less densely packed microstructure. (Xie et al., 2009) Thereafter, the ability of dental enamel to absorb energy and sustain deformation without catastrophic failure is attributed to its viscoelastic protein layers. Thus, the change in the protein content in teeth with MIH induces the enamel fracture when subjected to the masticatory efforts.

In relation to the dentin of MIH affected teeth it was observed that the Ca/P ratios for dentin below hypomineralized enamel were in principle identical to those of normal enamel; but when the Ca/C ratio was analyzed, dentin below hypomineralized enamel had the lowest values and the level of C was highest for dentin below hypomineralized enamel. In addition, O and P levels in dentin below normal enamel were higher compared with values in dentin below hypomineralized and N values for dentin below hypomineralized enamel are the highest. (Heijs et al., 2007)

This enhanced knowledge concerning the microstructural changes in hypomineralised enamel improves the understanding of some of the problems associated with the clinical management of these teeth. In particular, the frequent occurrence of enamel fractures and inadequate retention of adhesive materials both of which are recognized as significant clinical challenges preventing successful restoration of these compromised teeth. It is known that organic matter such as proteins have poor acid solubility. The presence of increased amounts of organic matter in the hypomineralised enamel, specifically within both prism structure and sheath regions may inhibit the creation of an adequate etch profile which in turn compromises the adhesion between resin based restorative materials and the defective enamel. (William et al., 2006b) Improved clinical outcomes are likely to depend, at least in part, on the successful treatment of these proteins prior to any enamel etching or adhesive strategies. (Baroni & Marchionni, 2011, Xie et al., 2008)


**7. Conclusions**

The above analyses have essentially, though not all in the same way, confirmed the legitimacy of the three hypotheses made at the outset.

From the perspective of political science, it seems no longer possible to maintain that fundamentalism is a strictly religious phenomenon. Both the studies into religious fundamentalism analysed and documented manifestations of secular fundamentalism lead to the conclusion that it is simply a specific way of thinking and acting which may develop and thrive just as well in secular as in religious soil. Its specific feature is the aspiration, anchored in an absolutist, selective and Manichean mindset, to establish an ideal order, which even justifies the use of violence. Fundamentalism as such is not necessarily related to religion, and—as demonstrated by history—has also thrived in atheist and anti-religious systems.

Additionally, the second hypothesis, namely that secularisation contributes to both secular and religious fundamentalist tendencies, has proved to be well-substantiated. As has been demonstrated, while secularisation in the West generates reactions of angry religiousness in other cultures (e.g., Islam or Hinduism), in the context of Western culture it contributes to the development of secular fundamentalisms, supporting the idea of unconstrained politics, and thus the hope for immanentising salvation, too. In this aspect, the analyses presented above suggest that it is necessary to broaden the meaning of the traditional modernisation hypothesis which considers only religious fundamentalism to be a reaction to the process of secularisation.

With regards to the third hypothesis, it should be noted that—on the theoretical level—the above analyses have confirmed that religion potentially represents a unique safeguard against fundamentalism, with practically nothing to substitute for it. By providing an ethical grounding for the political order, particularly by warranting an eschatological distance from political issues, it prevents the kingdom of man being confused with the kingdom of God, thus discarding the fundamentalist logic at its very roots. At the same time, the analyses have revealed two key conditions which must be satisfied if a religion is to provide such a barrier: firstly, it must understand itself as a rational religion; and secondly, it must clearly distinguish spiritual from secular power. Consequently, the analyses have shown that, regarding the actual role of religion as a safeguard against fundamentalism, the hypothesis is a medium-range claim, explaining in the contemporary context—in relation to the major religious traditions—first of all the role of Christianity, especially Catholicism, with respect to fundamentalist tendencies. In fact, the religions of the world are religions of reason to a very different degree, and they are often not interested in introducing a separation between spiritual and secular power. The above analyses have shown that, in the context of Islam where the vision of God is largely arbitrary and unpredictable, and where religion and politics are closely intertwined, fundamentalism could be, essentially, a natural product of the religious tradition. In the context of Western Christianity, where the separation between secular and spiritual power is—generally—an obvious principle, a different attitude to reason in religion may explain the higher fundamentalist potential of Protestantism than of Catholicism.

**Funding:** This research received no external funding.

**Conflicts of Interest:** The author declares no conflict of interest.


4. Conclusions

Property Value Unit Property Value Unit qt 3000 RB/DAY Bo 1.003 RB/STB h 60 ft Bw 1.002 RB/STB rw 0.35 ft co 8 106 1/psi re 6800 ft cw 3:02 106 1/psi k 300 ft cr 5 106 1/psi s 0 mD μo 3.0 cp Siw 0.10 μw 0.5 cp

pi 2500 psi pt 0.5 psi

Figure 13. Comparison of the wellbore pressure response from analytical solution and IMEX during water injection test

Figure 14. The log-log diagnostic plots for wellbore pressure data (blue curve) and its derivative with respect to time (red

Sor 0.25 λ 2

134 Perturbation Methods with Applications in Science and Engineering

Table 1. Reservoir, rock, and fluid properties for simulation and analytical solution.

ϕ 0.22

with capillary pressure (a).

curve) during water injection (b).

In this work, an accurate approximate analytical solution was constructed for wellbore pressure during water injection test in a reservoir containing oil and immobile water. Our solution was validated by comparing the bottom hole pressure calculated from the analytical model with the data obtained from a commercial numerical simulator. Our solution presented here for water injection together with the wellbore pressure and flow rate history for subsequent tests as shut-in and flowback can be used as forward model in a nonlinear regression in order to estimate relative permeabilities and capillary pressure curves in addition to the rock absolute permeability, the skin zone permeability, and the water endpoint relative permeability.


*Article* **Patent Analysis on the Development of the Shale Petroleum Industry Based on a Network of Technological Indices**

#### **Jong-Hyun Kim and Yong-Gil Lee \***

Department of Energy Resources Engineering, Inha University, 100 Inharo, Nam-gu, Incheon 22212, Korea<EMAIL_ADDRESS>
**\*** Correspondence<EMAIL_ADDRESS>Tel.: +82-32-860-7555

Received: 2 November 2020; Accepted: 16 December 2020; Published: 21 December 2020

**Abstract:** This study investigated the technological developments in the shale petroleum industry by analyzing patent data using a network of technological indices. The technological developments were promoted by the beginning of the shale industry, and after the first five years, it showed a more complex development pattern with the convergence of critical technologies. This paper described progress in the shale petroleum technologies as changes in relatedness networks of technological components. The relatedness represents degree of convergence between technological components, and betweenness centrality of network represents priority of technological components. In the results, the progress of the critical technologies such as directional drilling, increasing permeability, and smart systems, were actively carried out from 2012 to 2016. Especially, unconverged technology of increasing permeability and the converged technology of directional drilling and smart system has been intensively developed. Some technological components of the critical technologies are more significant in the form of converged technology.

**Keywords:** shale gas; tight oil; shale petroleum; technological development; patent; network analysis


*Article* **5-Fluorouracil-Loaded Folic-Acid-Fabricated Chitosan Nanoparticles for Site-Targeted Drug Delivery Cargo**

**Shafi Ullah 1,†, Abul Kalam Azad 2,\*,†, Asif Nawaz 1 , Kifayat Ullah Shah 1, Muhammad Iqbal 1 , Ghadeer M. Albadrani 3 , Fakhria A. Al-Joufi 4 , Amany A. Sayed 5 and Mohamed M. Abdel-Daim 6,7,\***

**Abstract:** Nanoparticles play a vital role in cancer treatment to deliver or direct the drug to the malignant cell, avoiding the attacking of normal cells. The aim of the study is to formulate folicacid-modified chitosan nanoparticles for colon cancer. Chitosan was successfully conjugated with folic acid to produce a folic acid–chitosan conjugate. The folate-modified chitosan was loaded with 5-FU using the ionic gelation method. The prepared nanoparticles were characterized for size, zeta potential, surface morphology, drug contents, entrapment efficiency, loading efficiency, and in vitro release study. The cytotoxicity study of the formulated nanoparticles was also investigated. The conjugation of folic acid with chitosan was confirmed by FTIR and NMR spectroscopy. The obtained nanoparticles were monodispersed nanoparticles with a suitable average size and a positive surface charge. The size and zeta potential and PDI of the CS-5FU-NPs were 208 ± 15, 26 ± 2, and +20 ± 2, respectively, and those of the FA-CS-5FU-NPs were 235 ± 12 and +20 ± 2, respectively, which are in the acceptable ranges. The drug contents' % yield and the %EE of folate-decorated NPs were 53 ± 1.8% and 59 ± 2%, respectively. The in vitro release of the FA-CS-5FU-NPs and CS-5FU-NPs was in the range of 10.08 ± 0.45 to 96.57 ± 0.09% and 6 ± 0.31 to 91.44 ± 0.21, respectively. The cytotoxicity of the nanoparticles was enhanced in the presence of folic acid. The presence of folic acid in nanoparticles shows much higher cytotoxicity as compared to simple chitosan nanoparticles. The folate-modified nanoparticles provide a potential way to enhance the targeting of tumor cells.

**Keywords:** colon cancer; targeted delivery; folate-conjugated nanoparticles; cytotoxicity


**Author details**

Antonio Thomas\*, Renato Passaro and Ivana Quinto Department of Engineering, University of Naples Parthenope, Italy

\*Address all correspondence to<EMAIL_ADDRESS>
© 2019 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.

**105**

2010;**35**:255-264

*Developing Entrepreneurship in Digital Economy: The Ecosystem Strategy for Startups Growth*

[11] Feld B. Startup Communities: Building an Entrepreneurial Ecosystem in Your City. New York: Wiley; 2012

[12] Carland JW, Hoy FS, Boulton WR, Carland JC. Differentiating entrepreneurs from small business owner: A conceptualization. Academy of Management Review. 1984;**9**(2):354-358

[13] Gartner WB. What are we talking about when we talk about entrepreneurship? Journal of Business

Venturing. 1990;**5**(1):15-28

Hall; 2010

2014;**23**:113-143

[14] Storey DJ, Greene F. Small Business and Entrepreneurship. Harlow: Prentice

[15] Nightingale P, Coad A. Muppets and gazelles: Political and methodological biases in entrepreneurship research. Industrial and Corporate Change.

[16] OECD. High-growth Enterprises: What Governments Can Do to Make a Difference. Paris: OECD Studies on SMEs and Entrepreneurship; 2010

[17] OECD. Financing High Growth Firms: The Role of Angel Investors. Paris: OECD Publishing; 2011

[18] Acs ZJ, Muller P. Employment effects of business dynamics: Mice, gazelles and elephants. Small Business

[19] Mason C, Brown R. Creating good public policy to support high growth firms. Small Business Economics.

[20] Brown R, Mason C. Inside the hightech black box: A critique of technology entrepreneurship policy. Technovation.

[21] Passaro R, Quinto I, Thomas A. Start-up competitions as

Economics. 2008;**30**(1):85-100

2013;**40**:211-225

2014;**3412**:773-784

*DOI: http://dx.doi.org/10.5772/intechopen.85423*

[1] van Stel A, Carree MA, Thurik R. The effect of entrepreneurial activity on national economic growth. Small Business Economics. 2005;**24**(3):311-321

[2] Audretsch DB, Keilbach MC, Lehmann EE. Entrepreneurship and Economic Growth. New York: Oxford

[3] Autio E, Kenney M, Mustar P, Siegel D, Wright M. Entrepreneurial innovation: The importance of context. Research Policy. 2014;**43**(7):1097-1108

[4] Bosma N, Acs ZJ, Autio E, Coduras A, Levie J, Global Entrepreneurship Monitor. Global Report. Babson Park, MA, USA: Babson College; 2008.

[5] OECD. An international benchmarking analysis of public programmes for high-growth firms. In:

LEED Programme; Paris. 2013

as job creators: A survey and

Institution; 2014

[6] Henrekson M, Johansson D. Gazelles

interpretation of the evidence. Small Business Economics. 2010;**35**:227-244

[7] Hathaway I, Litan R. Declining Business Dynamism in the United States: A Look at States and Metros. Washington, D.C.: The Brookings

[8] Mason C, Brown R. Entrepreneurial Ecosystems and Growth Oriented Entrepreneurship. The Hague, Netherlands: OECD; 2014

[9] Shane S. Why encouraging more people to become entrepreneurs is bad public policy. Small Business Economics. 2009;**33**(2):141-149

[10] Lerner J. The future of public efforts to boost entrepreneurship and venture capital. Small Business Economics.

University Press; 2008

p. 2009

**References**

*Developing Entrepreneurship in Digital Economy: The Ecosystem Strategy for Startups Growth DOI: http://dx.doi.org/10.5772/intechopen.85423*


Author details

Andreea Mihailescu

Address all correspondence to<EMAIL_ADDRESS>
Lasers Department, National Institute for Lasers, Plasma and Radiation Physics, Bucharest-Magurele, Romania


*Operations Management - Emerging Trend in the Digital Era*

creative economy process functionality and performance as well, while they play a role of go between elements social, between MIC and CE Processes as well.

The EN-S1 subsystem structure and functionality is being discussed within previous sections and the EN-S2 subsystem structure and functionality will be

*System of Data Transfer from and to Social and Economic Processes via Creative Economy…*

The principal layout of Economic Network structure is shown in **Figure 8**.

The Economic Network system (EN System) plays a role of information and knowledge-based supporting facility for CE, MIC, and MAC Processes. However, the EN System provides services related to KPI creation and decomposition, which is important for business strategy design within MIC and CE processes as well and is being designed as an information system and as a knowledge-based system too. On

respected within EN System design and implementation, while a selected GraphDB [31] system will be applied for EN System design and implementation and an

At present, the creative economy seems to a new branch, which provides interconnection between cultural standardized economy sphere and includes different activities related to culture and cultural heritage creation and management. However, providing those activities requires intellectual, material, and financial support as well, while all of them are closely related to macroeconomy and microeconomy objectives. On the other hand, the creative economics processes are the business processes too. However, they have adequate vertical and horizontal structure require an appropriate information, knowledge-based and organization support as well in order to assure their proper and efficient functionality, while their information support and metrics elements are closely related to each other. As a result of that the data or information transfer plays a role of principal importance and is running in two stages: (a) from creative economy to microeconomy BPs and (b) from microeconomy to macroeconomy BPs. Of course, the data transfer from DTS System external area represented by social and macroprocesses to CE Processes play an important role as well, while a set of MIC Processes represent an appropriate gobetween element and an integral part of sensors and effectors, acting within grey

The above-mentioned DTS System implemented via appropriate economic network, which seems to be relatively independent system and consist subsystems covering data transfer within CE, Micro and Macroprocesses (EN-S1 Subsystem)

The above-mentioned stages are being implemented and operated via appropriate economic networks, the (a) phase activities are covered by economic network I and the (b) phase are covered by economic network II. Both above-mentioned economic network subsystems should be implemented and operated via adequate

zone, which exists between BP external and internal environment.

and Macro, Micro and CE Processes (EN-S2 Subsystem) as well.

one hand, when considering the information system, the linguistic sets are implemented as standardized database tables, on the other hand, considering the knowledge based system the linguistic sets create basis of adequate reference databases and play a role semantic network elements. When considering the user's communication with the information system an appropriate database management system for those purposes should be applied and when considering the user's communication with an adequate knowledge-based system an appropriate inference system is used for those purposes. The above-mentioned aspects should be

discussed within individual and independent contribution.

**10. Design and implementation aspects**

*DOI: http://dx.doi.org/10.5772/intechopen.94006*

adequate application program should be created.

**11. Discussion**

**119**

The **EN-S2 Subsystem** is being covered by **EN\_S2\_01 Macroprocesses** component, which consists of the following modules: (a) Normative act processing, (b) Document semantic analysis, (c) Datamining execution, (d) KPI creation and (d) KPI execution.

However, the **EN-S2 Subsystem** is being covered by **EN\_S2\_02 Microprocesses** component, which consists of the following modules: (a) MIC Process – KPI Setting and (b) MIC Process – Metrics Indicator Setting as well, while the latest component is denoted as EN-S2-03 CE Process, which consists of the following modules: (a) CE15 Process KPI Setting and (b) CE Process – Metrics Indicator Setting, and CHA16 Process – Metrics Indicator Setting.

#### **Figure 8.**

*The principal layout of Economic Network structure. Source: The Authors.*

15 CE—Creative Economy.

16 CHA—Cultural Heritage Administration.

*System of Data Transfer from and to Social and Economic Processes via Creative Economy… DOI: http://dx.doi.org/10.5772/intechopen.94006*

The EN-S1 subsystem structure and functionality is being discussed within previous sections and the EN-S2 subsystem structure and functionality will be discussed within individual and independent contribution.

The principal layout of Economic Network structure is shown in **Figure 8**.

## **10. Design and implementation aspects**

The Economic Network system (EN System) plays a role of information and knowledge-based supporting facility for CE, MIC, and MAC Processes. However, the EN System provides services related to KPI creation and decomposition, which is important for business strategy design within MIC and CE processes as well and is being designed as an information system and as a knowledge-based system too. On one hand, when considering the information system, the linguistic sets are implemented as standardized database tables, on the other hand, considering the knowledge based system the linguistic sets create basis of adequate reference databases and play a role semantic network elements. When considering the user's communication with the information system an appropriate database management system for those purposes should be applied and when considering the user's communication with an adequate knowledge-based system an appropriate inference system is used for those purposes. The above-mentioned aspects should be respected within EN System design and implementation, while a selected GraphDB [31] system will be applied for EN System design and implementation and an adequate application program should be created.

### **11. Discussion**

creative economy process functionality and performance as well, while they play a

The **EN-S2 Subsystem** is being covered by **EN\_S2\_01 Macroprocesses** component, which consists of the following modules: (a) Normative act processing, (b) Document semantic analysis, (c) Datamining execution, (d) KPI creation and (d)

role of go between elements social, between MIC and CE Processes as well.

*Operations Management - Emerging Trend in the Digital Era*

However, the **EN-S2 Subsystem** is being covered by **EN\_S2\_02**

Indicator Setting, and CHA16 Process – Metrics Indicator Setting.

**Microprocesses** component, which consists of the following modules: (a) MIC Process – KPI Setting and (b) MIC Process – Metrics Indicator Setting as well, while the latest component is denoted as EN-S2-03 CE Process, which consists of the following modules: (a) CE15 Process KPI Setting and (b) CE Process – Metrics

KPI execution.

**Figure 8.**

**118**

15 CE—Creative Economy.

16 CHA—Cultural Heritage Administration.

*The principal layout of Economic Network structure. Source: The Authors.*

At present, the creative economy seems to a new branch, which provides interconnection between cultural standardized economy sphere and includes different activities related to culture and cultural heritage creation and management. However, providing those activities requires intellectual, material, and financial support as well, while all of them are closely related to macroeconomy and microeconomy objectives. On the other hand, the creative economics processes are the business processes too. However, they have adequate vertical and horizontal structure require an appropriate information, knowledge-based and organization support as well in order to assure their proper and efficient functionality, while their information support and metrics elements are closely related to each other. As a result of that the data or information transfer plays a role of principal importance and is running in two stages: (a) from creative economy to microeconomy BPs and (b) from microeconomy to macroeconomy BPs. Of course, the data transfer from DTS System external area represented by social and macroprocesses to CE Processes play an important role as well, while a set of MIC Processes represent an appropriate gobetween element and an integral part of sensors and effectors, acting within grey zone, which exists between BP external and internal environment.

The above-mentioned DTS System implemented via appropriate economic network, which seems to be relatively independent system and consist subsystems covering data transfer within CE, Micro and Macroprocesses (EN-S1 Subsystem) and Macro, Micro and CE Processes (EN-S2 Subsystem) as well.

The above-mentioned stages are being implemented and operated via appropriate economic networks, the (a) phase activities are covered by economic network I and the (b) phase are covered by economic network II. Both above-mentioned economic network subsystems should be implemented and operated via adequate

Datawarehouse system, where the economic network subsystems EN-S1 and EN-S2 could be implemented via Datamart I and Datamart II and both have their own ETL systems, which provide extraction of data from appropriate linguistic sets (E), the data transformation (T) to pre-defined structure of multidimensional tables and data loading (L) to the above DataMart I and Datamart II. On the other hand, there is an appropriate OLAP system, which should enable providing data selection and analysis with respect to authorized user requirements. Moreover, that system could contain a software, which enables providing a semantic analysis of EU documents and extracting data, which are inserted into a software, which prepares supporting data concerned to business strategy of the firm or company, which deals with creative economy activities.


**Acknowledgment**

Author would like to express his thanks to Mr. H. Terashima, Ms. Y. Zhang, Mr. T. Maruyama, and Mr. S. Hironaka for their engagement as master course research in Graduate School of Fukuoka Institute of Technology, Fukuoka, Japan from 2010 to 2012.


**6. References**

Fukuchi-Shimogori T, Grove EA. 2003. Emx2 patterns the neocortex by regulating FGF

Gong S, Kus L, Heintz N. 2010. Rapid bacterial artificial chromosome modification for large-

Gong S, Zheng C, Doughty ML, Losos K, Didkovsky N, Schambra UB, Nowak NJ, Joyner A,

Hamasaki T, Leingärtner A, Ringstedt T, O'Leary DD. 2004. EMX2 regulates sizes and

Heiman M, Schaefer A, Gong S, Peterson JD, Day M, Ramsey KE, Suárez-Fariñas M,

Hirokawa J, Watakabe A, Ohsawa S, Yamamori T. 2008. Analysis of area-specific expression

Inoue T, Inoue YU, Asami J, Izumi H, Nakamura S, Krumlauf R. 2008a. Analysis of mouse

Inoue T, Tanaka T, Suzuki SC, Takeichi M. 1998. Cadherin-6 in the developing mouse brain:

Inoue YU, Asami J, Inoue T. 2008b. Cadherin-6 gene regulatory patterns in the postnatal

Inoue YU, Asami J, Inoue T. 2009. Genetic labelling of mouse rhombomeres by Cadherin-

Jabaudon D, J Shnider S, J Tischfield D, J Galazo M, Macklis JD. 2011. ROR{beta} Induces Barrel-like Neuronal Clusters in the Developing Neocortex. Cereb Cortex. Kiecker C, Lumsden A. 2005. Compartments and their boundaries in vertebrate brain

Krishna-K, Nuernberger M, Weth F, Redies C. 2009. Layer-specific expression of multiple

Lee EC, Yu D, Martinez de Velasco J, Tessarollo L, Swing DA, Court DL, Jenkins NA,

Livet J, Weissman TA, Kang H, Draft RW, Lu J, Bennis RA, Sanes JR, Lichtman JW. 2007.

Leblanc G, Hatten ME, Heintz N. 2003. A gene expression atlas of the central nervous system based on bacterial artificial chromosomes. Nature. 425:917-925. Gumbiner BM. 2005. Regulation of cadherin-mediated adhesion in morphogenesis. Nat Rev

positioning of the primary sensory and motor areas in neocortex by direct

Schwarz C, Stephan DA, Surmeier DJ, Greengard P, Heintz N. 2008. A translational profiling approach for the molecular characterization of CNS cell types. Cell.

patterns of RORbeta, ER81 and Nurr1 mRNAs in rat neocortex by double in situ

Cdh6 gene regulation by transgenesis of modified bacterial artificial chromosomes.

expression along restricted connection systems and synaptic localization suggest a

6::EGFP-BAC transgenesis underscores the role of cadherins in hindbrain

cadherins in the developing visual cortex (V1) of the ferret. Cereb Cortex. 19:388-

Copeland NG. 2001. A highly efficient Escherichia coli-based chromosome engineering system adapted for recombinogenic targeting and subcloning of BAC

Transgenic strategies for combinatorial expression of fluorescent proteins in the

positional signalling. Nat Neurosci. 6:825-831.

Mol Cell Biol. 6:622-634.

135:738-748.

401.

Dev Biol. 315:506-520.

scale mouse transgenesis. Nat Protoc. 5:1678-1696.

specification of cortical progenitors. Neuron. 43:359-372.

hybridization and cortical box method. PLoS One. 3:e3266.

potential role in neuronal circuitry. Dev Dyn. 211:338-351.

mouse brain. Mol Cell Neurosci. 39:95-104.

compartmentalization. Neurosci Res. 63:2-9.

development. Nat Rev Neurosci. 6:553-564.

DNA. Genomics. 73:56-65.

nervous system. Nature. 450:56-62.

Zhang F, Aravanis AM, Adamantidis A, de Lecea L, Deisseroth K. 2007. Circuit-breakers: optical technologies for probing neural signals and systems. Nat Rev Neurosci. 8:577-581.


**KEY ISSUES FOR MANAGEMENT OF INNOVATIVE PROJECTS**

Edited by **Bernardo Llamas Moya, M. Dolores Storch de Gracia** and **Luis F. Mazadiego**

#### **Key Issues for Management of Innovative Projects**

http://dx.doi.org/10.5772/64899 Edited by Bernardo Llamas Moya, M. Dolores Storch de Gracia and Luis F. Mazadiego

#### **Contributors**

Angela Albu, Riaz Ahmed, Leonid Mylnikov, Blanka Bazsova, Radul Milutinović, Biljana Stošić, Florin Boghean, Carolina Rodriguez Rodriguez, Amador Cernuda, María Dolores Storch De Gracia, Manuel Irun, Jose Miguel Munoz Perez

#### **© The Editor(s) and the Author(s) 2017**

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, 2017 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>
Key Issues for Management of Innovative Projects Edited by Bernardo Llamas Moya, M. Dolores Storch de Gracia and Luis F. Mazadiego p. cm. Print ISBN 978-953-51-3467-1 Online ISBN 978-953-51-3468-8 eBook (PDF) ISBN 978-953-51-4681-0


**β-Endorphin and Alcoholism**

Sarah M. Barry1 and Judith E. Grisel2

*1Department of Neurosciences, The Medical University of South Carolina, Charleston, SC, 2Neuroscience Program, Department of Psychology, Furman University, Greenville, SC, USA*


**Author details**

Rachid Zegait1 \*, Saber Kouadri2 , Samir Kateb2 and Mohamed Azlaoui1

1 Faculty of Science and Technology, Ziane Achour-Djelfa University, Algeria

2 Faculty of Applied Sciences, Kasdi Merbah-Ouargla University, Algeria

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

*Reliability and Problems of Wastewater Treatment Processes in the Algerian Sahara DOI: http://dx.doi.org/10.5772/intechopen.96113*


**2. Surgical approach**

The surgical technique for RTSA can be accomplished via two approaches: deltopectorally or superolaterally [3, 9]. The deltopectoral approach is the most common and requires an experienced surgeon [10]. This surgical technique begins with an incision overlying the deltopectoral interval, preserving the cephalic vein, then tenotomizing the biceps tendon and the subscapularis if still intact [3, 11, 12].  The humeral head is then reamed and broached. Subsequently, the glenoid is exposed, the labrum excised, and the glenoid prepared. The guidewire for the glenoid reamer is placed inferiorly so that the glenoid baseplate will be flush with the inferior border of the native glenoid rim. This will help decrease the risk of scapular notching. By adding an inferior tilt to the position of the baseplate, the risk of scapular notching can be decreased, which in turn, improves compressive forces and helps avoid shear forces on the glenoid component. The baseplate is impacted in place, and secured with screws to securely fix the baseplate to the patient's native glenoid. The selected glenosphere is then secured to the baseplate with a Morse Taper fixation mechanism. The selection of the appropriately sized glenosphere is multifactorial. It is based on the patient's size (i.e., 42 mm for larger patients, 39 mm for average size patients, 36 mm for smaller patients) and individual patient pathologies. Glenosphere components are available in central, lateral offset, and inferior offset designs.

Next, the humeral stem is prepared by sounding the inner diameter of the humeral shaft and broaching it to the appropriate size. The final implant is tested with the spacer trials in order to gain proper stability and range of motion. Then the real implants are seated and the shoulder is reduced. Lastly, the subscapularis is reattached and the biceps are tenodesed with heavy nonabsorbable sutures that are placed through drill holes in the humeral metaphysis prior to seating of the final implant. However, recent research acknowledges the controversy surrounding the reattachment of the subscapularis due to the potential for increasing the likelihood of dislocation [13]. The deltopectoral-interval is re-approximated and the incision closed. The patient is placed in a shoulder abduction sling for a period of immobilization lasting two to 6 weeks with a home physical therapy program [14]. As with all orthopedic procedures, the rehabilitation protocol is patient specific and additional rehabilitation may be deemed necessary if the patient needs to strengthen external rotation [14].


**7. Design of multimodal reconfigurable microwave and mm-wave circuits**

This section presents two applications of the RF-MEMS presented in Section 5 when combined with the multimodal circuits presented in Section 2: 180° phase switches and bandpass filters. All of them were fabricated using the process described in Section 3.

#### **7.1. Phase switches**

A 180° phase switch is a circuit that shifts the phase between 0 and 180°. This is a multi-purpose element required in the microwave and millimeter-wave applications, such as high-sensitivity radiometers or electronic beam steering in phased-array antennas. The specifications for these systems are, in most cases, a broadband operation, a low power consumption, and small size. They can be implemented monolithically using HBT/HEMT-based MMICs or using MEMSbased solutions as shown subsequently.

**Figure 21(a)** shows a compact, uniplanar 180° phase switch fabricated on a quartz substrate [9]. It is based on two different back-to-back (BTB) CPW-to-slotline transitions [39] (symmetric and antisymmetric transitions, respectively), creating two phase paths with a relative transmission phase shift between them of 180°. Each path is selected using two single-pole-doublethrow (SPDT) switches. The SPDT consists of two ohmic-contact MEMS series switches

**Figure 21.** (a) Manufactured 180° phase switch. (b) Measured insertion loss (symmetric and antisymmetric paths) and measured phase shift between the two paths.

(described in Section 5.2.2) and a power divider. **Figure 21(b)** shows the measured performance of the circuit, featuring a 180° ± 5° phase shift between both states in a bandwidth of 35% (14–20 GHz), with an insertion loss smaller than 2 dB in both paths.

**Figure 22(a)** shows the photograph of a second compact, uniplanar 180° phase switch fabricated on a quartz substrate [10]. In this case, it is based on an air-bridged CPW cross [57]. The two CPW arms of the cross are loaded with capacitive-contact MEMS switches (described in Section 5.2.1). The two phase-switch states (0°/180°) are obtained by actuating the MEMS switches in opposite states (ON/OFF and OFF/ON), resulting in a multimodal interaction between the two CPW modes (even and odd) at the air-bridged cross. The CPW-to-slotline transition [39] at the input port and the CPW taper at the output port are included in order to enable the measurement of the circuit with a probe station. **Figure 22(b)** shows the measured results of phase shift between both states and insertion loss, featuring 180° +1.8°/−1° and ± 0.1 dB insertion-loss unbalance, respectively, in a very wide bandwidth (5–25 GHz). The measured insertion loss is better than 2 dB in 10–20-GHz frequency band.

#### **7.2. Uniplanar bandpass filters**

In **Table 2**, the values of the equivalent circuit elements obtained to fit measurement are listed. The capacitive switch features a high capacitance ratio (*CON*/*COFF* = 50.2). The ohmic switches feature low insertion loss (<1 dB) and high isolation (>20 dB) for f < 10 GHz (parallel switch)

This section presents two applications of the RF-MEMS presented in Section 5 when combined with the multimodal circuits presented in Section 2: 180° phase switches and bandpass

A 180° phase switch is a circuit that shifts the phase between 0 and 180°. This is a multi-purpose element required in the microwave and millimeter-wave applications, such as high-sensitivity radiometers or electronic beam steering in phased-array antennas. The specifications for these systems are, in most cases, a broadband operation, a low power consumption, and small size. They can be implemented monolithically using HBT/HEMT-based MMICs or using MEMS-

**Figure 21(a)** shows a compact, uniplanar 180° phase switch fabricated on a quartz substrate [9]. It is based on two different back-to-back (BTB) CPW-to-slotline transitions [39] (symmetric and antisymmetric transitions, respectively), creating two phase paths with a relative transmission phase shift between them of 180°. Each path is selected using two single-pole-doublethrow (SPDT) switches. The SPDT consists of two ohmic-contact MEMS series switches

**Figure 21.** (a) Manufactured 180° phase switch. (b) Measured insertion loss (symmetric and antisymmetric paths) and

**7. Design of multimodal reconfigurable microwave and mm-wave**

filters. All of them were fabricated using the process described in Section 3.

and for f < 25 GHz (series switch).

138 MEMS Sensors - Design and Application

based solutions as shown subsequently.

measured phase shift between the two paths.

**circuits**

**7.1. Phase switches**

**Figure 23(a)** shows a second-order bandwidth-reconfigurable bandpass filter, which was fabricated on a quartz substrate (*h* = 500 μm) [11]. The *λo /2* slotline resonators are coupled by a slotline short-circuit (*K*12). The filter features multimodal immittance inverters (MIIs) based on CPW-to-slotline transitions [37, 58] which are embedded in the input and output slotline resonators. As shown in **Figure 23(b)**, two cantilever-type ohmic-contact MEMS switches (described in Section 5.1) are used to enable reconfigurable MIIs. When actuated, the switches modify the input and output coupling of the filter (*K*01 and *K*23), resulting in a change in the filter's fractional bandwidth (FBW). To keep the central frequency constant, another cantilever MEMS switch (also shown in **Figure 23(b)**) is integrated in *K*12 and actuated simultaneously. **Figure 23(c)** shows the filter measured results. It features two FBW states of 0.082 (when the inner switches are actuated) and 0.043 (when the outer switches and the impedance inverter switch are actuated), while maintaining a constant center frequency (18.9 GHz).

**Figure 24(a)** shows a second-order bandpass filter fabricated on a 5-KΩ-cm high-resistivity silicon substrate (εr = 11.9, *h* = 200 μm), which uses switchable air bridges or SABs [6] (shown in **Figure 24(b)**) similar to the SAB of **Figure 14(a)**. The SABs are described in Section 5.2.3. Like

**Figure 22.** (a) Manufactured 180° phase switch. (b) Measured insertion loss for the two states and phase shift between the two states.

filter measured results. It features two operating frequencies, *f*

**8. Conclusion**

showing excellent performances.

\*, David Girbau2

**Acknowledgements**

AEI, Spain.

**Author details**

Adrián Contreras1

Benno Margesin5

Lluis Pradell1

a constant fractional bandwidth (FBW) of 14%. The measured filter IL is 4.6 dB in both states.

RF-MEMS Switches Designed for High-Performance Uniplanar Microwave and mm-Wave Circuits

In this chapter, the design considerations of RF-MEMS switches aimed to be integrated in uniplanar multimodal reconfigurable circuits for operation in the microwave and mm-wave bands have been presented. Different configurations of series and parallel switches featuring ohmic and capacitive contact have been discussed in detail, including the analysis of mechanical topologies which minimize the initial deformation due to residual stress. The fabrication process has been described, which provides the required flexibility to integrate the MEMS switches into higher-level RF communication systems. The switch RF behavior has been modeled using suitable equivalent circuits for both (ON/OFF) switch states. The models can easily be embedded into complex multimodal environments which enable multipurpose, compact designs. The fabricated switches have been experimentally characterized in terms of hysteresis, RF isolation (OFF state), and RF insertion loss (ON state), demonstrating an excellent behavior. As practical examples of the application into communication systems, some of the proposed switches have successfully been integrated into 0°/180° phase switches and into reconfigurable filters with either center frequency or fractional-bandwidth reconfiguration,

This work was supported by the Spanish MEC under Projects TEC2013-48102-C2-1/2-P, TEC2016-78028-C3-1-P and grant BES-2011-051305, the Mexican CONACYT under fellowship 410742, and the Unidad de Excelencia Maria de Maeztu MDM-2016-0600 financed by the

, Jasmina Casals-Terré4

, Julio Heredia1

1 Department of TSC, Technical University of Catalonia (UPC), Barcelona, Catalonia, Spain

, Antonio Lázaro2

, Flavio Giacomozzi5

,

and

, Miquel Ribó3

2 Department of EEEA, Rovira i Virgili University, Tarragona, Catalonia, Spain

3 Department of ET, La Salle-Ramon Llull University, Barcelona, Catalonia, Spain

, Marco Antonio Llamas1

\*Address all correspondence to<EMAIL_ADDRESS>
4 Department of EM, UPC, Barcelona, Catalonia, Spain

5 Fondazione Bruno Kessler, Trento, Italy

0 = 12 GHz and *f*

http://dx.doi.org/10.5772/intechopen.76445

0 = 13 GHz, with

141

**Figure 23.** (a) Second-order bandwidth-reconfigurable bandpass filter. (b) Detail of reconfigurable MIIs and reconfigurable inductive coupling *K*12. (c) Filter measured insertion loss and return loss.

**Figure 24.** (a) Second-order frequency-reconfigurable bandpass filter. (b) Detail of reconfigurable MIIs and SAB. (c) Filter measured insertion loss and return loss.

the previous example, the filter is fed by reconfigurable MII structures with embedded CPWto-slotline transitions but uses quarter-wavelength resonators coupled by a slotline gap. When actuated, the SABs reduce the resonators' effective length, which in turn increases the resonance frequency. As a result, the filter center frequency is shifted up. **Figure 24(c)** shows the filter measured results. It features two operating frequencies, *f* 0 = 12 GHz and *f* 0 = 13 GHz, with a constant fractional bandwidth (FBW) of 14%. The measured filter IL is 4.6 dB in both states.


*Edited by Alessandro Rozim Zorzi and Joao Batista de Miranda*

Advanced Techniques in Bone Regeneration is a book that brings together over 15 chapters, written by leading practitioners and researchers, of the latest advances in the area, including surgical techniques, new discoveries, and promising methods involving biomaterials and tissue engineering. This book is intended for all who work in the treatment of disorders involving problems with the regeneration of bone tissue, are doctors or dentists, as well as are researchers and teachers involved in this exciting field of scientific knowledge.

ISBN 978-953-51-2538-9

Advanced Techniques in Bone Regeneration

Photo by eranicle / iStock