7. Results

In (Eq. (1)) one maximizes the ranking generated by the selected POIs. According to (Eq. (2)), a PoI must be visited after the current location. Constraints (Eq. (3)) enforce for the tourist to come back to the current location after the visit of the last PoI. Constraints (Eq. (4)) guarantee that a tourists arriving at any PoI must also leave from that PoI. Constrains (Eq. (5)) link decisions variables on POIs selections and movement between nodes. Constraints (Eq. (6)) are the subtour elimination constraints of Miller, Tucker, and Zemlin. Constraints (Eq. (7)) enforce that the overall time spent to move between nodes and visit POIs is lower that the planned time interval. Finally, (Eq. (8)), (Eq. (9)), and (Eq. (10)) are the domain of decision variables.

It is worth noting that one does not have to visit all nodes of the N, unless a large value of d is considered. Moreover, the direct graph makes very easy to model the case in which starting

Consider the subset N of nodes selected in the previous model. These nodes may not be visited in an effective order, as this model does not aim to minimize the costs of movement between nodes. To correct this drawback, we consider a second model, in which a formulation of the Traveling Salesman Problem (TSP) is presented. The solution of the TSP determined the so-

The TSP can be described as the following graph theoretic problem. Let G N; A � � be a direct and complete graph, where A the set of arcs connecting nodes of set N. The following decision

> X j ∈ N

In (Eq. (11)) one maximizes the ranking generated by the selected POIs. According to (Eq. (12)) and (Eq. (13)), a node must be visited before and after the current one, respectively. Constraints

ti,j � Xi,j (11)

Xi,j ¼ 1 ∀i∈ N (12)

Xj,i ¼ 1 ∀i∈ N (13)

� � >¼ 0 ∀ð Þ i; j ∈ A (14)

Xi,j ∈f g 0; 1 ∀ð Þ i; j ∈ A (15)

Ui ∈f g 0…N ∀i∈ N (16)

• Xi,j ∈f g 0; 1 is equal to 1 if the tourist moves along arc ð Þ i; j ∈ A, 0 otherwise;

MinX i ∈ N

X j ∈ N, j6¼i

X j ∈ N, j6¼i

Uj � Ui � 1 þ M � 1 � Xi,j

and arrival points are different.

44 Assistive Technologies in Smart Cities

called optimized itineraries mentioned throughout this paper.

• Ui ∈ 0;…; jNj � � is the position of POI i ∈ N in the current trip.

The problem can be formulated as follows:

6.2. Second model

variables are defined:

In this section we show the viability of the proposed tools to support the mobility of physically disabled tourists or elder persons. We also analyze the case of able-bodied tourists for the sake of comparison. The difference between the two cases is shown by increasing travel times along uphill and downhill routes for disabled tourists as opposed to able-bodied ones. The experimentation is carried out in the city of Cagliari, where many tourists disembark from cruise ships at the harbor. They typically aim to visit the oldest part of Cagliari, which is known as the Castello. It clings to the slopes of a hill that rises steeply from the harbor. Therefore, in this case study it is of particular relevance to distinguish between the waking times of disabled and able-bodies tourists, in order to properly plan which subset of PoI should be visited, as well as the order of the visit.

Four classes of PoIs are considered, which correspond to different profiles of tourists interested in museums, monuments, gardens or shops. We took their location and their altitude from the open data platform and we derived the average slope of the streets connecting PoIs. The average travel time per unitary distance was calibrated by a sample of tourists with similar disabilities over a set of streets with different slopes. Since the distance between all PoIs is known, we easily derived the travel times among them.

All the PoIs are ranked with a value ranging from 1, less attractive, to 5, most attractive. A subset of PoIs is considered for each class by a score threshold, which specifies the PoIs the tourist wants to visit. For example, if it taken on value 2, we consider all PoIs with a score bigger than or equal to 2. We initially set the score threshold to 3 and relax the constrain on (7) and compute the itineraries for each class of PoIs. In Figure 5 the time to visit all PoIs is reported for all class of PoIs in four cases:

Figure 5. Minimum time for optimized itineraries with threshold = 3.

As expected, it takes longer to make closed itineraries than open ones and the overall visiting time for disabled tourists is larger than that of able-bodied ones. Next, we reintroduce constrain (Eq. (7)) and plan itineraries according to settings of the time limit d and score threshold. More precisely:

Figure 6. Optimized itineraries with maximum time 120 min and threshold = 3.

• In the results of Figure 8, d is set to 120 min and the score threshold to 2; • In the results of Figure 9, d is set to 120 min and the score threshold to 4;

Figure 9. Optimized itineraries with maximum time 120 min and threshold = 4.

Figure 8. Optimized itineraries with maximum time 120 min and threshold = 2.

persons.

8. Conclusions and future work

The obtained results show that the proposed tools can be customized to return a subset of PoIs for physically disabled tourists as opposed to the set of routes determined for able-bodied

Using IoT for Accessible Tourism in Smart Cities http://dx.doi.org/10.5772/intechopen.77057 47

Within the framework of Smart Cities, Accessible Tourism and Internet-of-Things (IoT), this paper analyses the key requirements for IoT applications in a Smart City context, the

Figure 7. Optimized itineraries with maximum time 240 min and threshold = 3.

Figure 8. Optimized itineraries with maximum time 120 min and threshold = 2.

• Open itineraries of disabled tourists from a given GPS location to the port (blue rhombus); • Closed itineraries of disabled tourists leaving and returning back to the port (red square); • Open itineraries of able-bodied tourists from a given GPS location to the port (green triangle); • Closed itineraries of able-bodied tourists leaving and returning back to the port (gray cross). As expected, it takes longer to make closed itineraries than open ones and the overall visiting time for disabled tourists is larger than that of able-bodied ones. Next, we reintroduce constrain (Eq. (7)) and plan itineraries according to settings of the time limit d and score threshold.

• In the results of Figure 6, d is set to 120 min and the score threshold to 3; • In the results of Figure 7, d is set to 240 min and the score threshold to 3;

Figure 6. Optimized itineraries with maximum time 120 min and threshold = 3.

Figure 7. Optimized itineraries with maximum time 240 min and threshold = 3.

More precisely:

46 Assistive Technologies in Smart Cities

Figure 9. Optimized itineraries with maximum time 120 min and threshold = 4.

The obtained results show that the proposed tools can be customized to return a subset of PoIs for physically disabled tourists as opposed to the set of routes determined for able-bodied persons.

#### 8. Conclusions and future work

Within the framework of Smart Cities, Accessible Tourism and Internet-of-Things (IoT), this paper analyses the key requirements for IoT applications in a Smart City context, the state-of-the-art for the use of IoT for Accessible Tourism and presents an IoT architecture for the specific Smart City scenario dedicated to the sustainable management of the tourist flow in the urban environment of Cagliari. Based on the presented IoT architecture, a Tour Planner Application with features for accessible tourism is presented, together with the mathematical optimization model used for generating a specific tour including a subset of PoIs. The proposed application is tailored for persons with physical impairments. The results of the initial tests are presented and first conclusions are drawn. The obtained results showed that the proposed algorithm can be customized to return a subset of PoIs for disabled tourists as opposed to the set of routes determined for able-bodied tourists. The future work will be focused on refining the used algorithm by taking into considerations new accessibility constraints and also other types of input, such as for example live accessibility data from public transportation.

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final.pdf


**4. Final considerations**

In mouse model, treatment with G-CSF generates in the HSCT donors an increase of Treg cells, which may be responsible for the generation of suppressor neutrophils. When transferred to the HSCT receptors, these neutrophils are able to suppress the GVHD by reducing the clinical and histopathological signs of the disease. On the other hand, these protected individuals retain the anti-leukemia effect, which is important to prevent relapses, and reject allogeneic skin grafts, showing that the protection of GVHD is due to a specific suppression and not a systemic immunosuppression of the recipient, which claims for a T cell function.

The type of neutrophil generated after G-CSF treatment is obviously different from the classical neutrophil, known as inflammatory. Although activated and mature, they express low levels of MHC-II and co-stimulatory molecules, low levels of MPO, and are degranulated. On the other hand, they are producers of the suppressive cytokine IL-10 and also show an increase in IL-4 and IL-22. Together, these characteristics make this cell a potential suppressor, since several mechanisms able to modulate T cells are present.

We believe that after transfer to the recipient, these neutrophils (which have a longer half-life, as recently reported in the literature) rapidly colonize the sites activated by the conditioning regimen. It is known that in 3 days there is neutrophil colonization in mLN. Although reports in the literature associate this early neutrophil colonization with the increased damage caused by GVHD, this neutrophil is of a distinct subtype, generated after treatment with G-CSF. Thus, in these activated sites, neutrophils can act to control local inflammation, generating a regulatory environment, favoring the generation of new Treg cells that amplify the specific protection observed in our study.

We conclude that neutrophils function goes beyond the microbicidal function. The classical view is too narrow to explain the many features acquired by these cells. Many different and complex subtypes of regulatory neutrophils have been recently described. Although their characterization is not precise, regulatory neutrophils can be grouped together based on their functional profile. Also, the interaction between these neutrophils and other cell types, such as the ones described here (macrophages, NK, NKT, ILC, DC, B and T cells), potentiate the regulatory response in different conditions. So, the regulatory neutrophils confer an important bridge between innate and adaptive immune system in many different conditions, building a new role for an underestimated cell.


Immunomodulator in Traditional Healthcare System

*Shweta Saboo*

## **Abstract**

In all over world the importance of traditional medicine for the use as treatment against of life threatening diseases is acceptable. Due to heavy potency and availability of the natural sources it's easy to utilize this traditional knowledge for treatment, prevention or mitigation against diseases. In this chapter we discuss about different potent Immuno-modulating drugs which majorly act as immune stimulant. From the ancient time these drugs having potent active constituent which shown prominent effect in treatment of diseases. Considering efficiency with safety plant derived drugs having very global market this review discusses immunomodulating plant with their active constituent.

**Keywords:** traditional herbs, immunomodulators, medicinal plants

## **1. Introduction**

The Indian traditional system of medicine (Ayurveda) had important role in prevention and treatment of disease. Many of the plants showing effect as an immunomodulator. Though conventional immunomodulatory chemotherapy is available but it is costlier and is not usually affordable to ordinary people with loweconomic status [1]. Therefore, the modulation of immune system by traditional medicinal plant products has become a subject matter for current scientific investigations worldwide. A huge number of medicinal plants have been indicated in Siddha and Ayurveda classical literature towards the management of several diseases that results in immune deficiency. The present study summarized that the Ayurveda, siddha used as Immunomodulator in Health care system.

## **2. Immunity**

Immunity is the capability of the Multicellular organism to resist harmful microorganism .these microorganism act as foreign body for living cell, and it try to kill that microorganism. It is also called defense mechanism of the organism to protect from the external factor. Immunity involves both specific and nonspecific components. The nonspecific components act as fighter or barriers to the number of pathogens with various genetic makeup and its nature while specific type of immunity is produce only when specific type of Pathogen produce specific type of Infection and to resist it specific type of immune cell become active and produce resistant to that pathogens [2].

Immunity can be defined as a complex biological system of the body which having capacity to identify whatever belongs to cell or which is beneficial to body and resist to foreign or harmful material with the capacity to recognize and tolerate whatever belongs to the self, and to recognize and reject what is foreign (non-self) [2].

## **3. Immune cells has two distinct**

The basic architecture of the immune system is multi layered, with the Defense on several levels. First barrier is the skin, against the infection. Another is physiological conditions, where conditions like temperature and pH of the body provide in appropriate living condition for foreign organisms. Once pathogens have successfully entered in the body, they are addressed by the innate or acquired or adaptive immune system.

The immune system has two components: innate and adaptive immunity. The innate immunity is present in all metazoans, while the adaptive immunity only occurs in vertebrates.

The innate system after the stimulation of foreign material body produces Inflammation and phagocytosis. On the other side on adaptive system is composed with Lymphatic cell, these cells have ability to distinguish between self cell and non self cell [3].

The inflammation reaction is produce when foreign material enters into body and cells able to find out its foreign material.while The non-reaction to self substances is described as immunity - meaning to exempt.

These two action produce dynamic biological environment and it called health. Disease can occur when foreign material not eliminated or what is self is not spared [3].

### **4. Immuno modulators**

These are natural or synthetic compound or its combination which alter or modify both types of immune system either adaptive or innate of the body.

#### **5. Classification of an immunomodulators**

Imunoadjuants are used to enhance the efficiency of vaccines and therefore could be considered a specific immune stimulant. Imunoadjuants hold the promise of being the true modulator of the immune response. It has been proposed that they be exploited as selectors between cellular and humoral helpers [4].

Immunostimulants are inherently non specific as they are envisaged as enhancement to the resistance to the inspection. They act through the intent as well as adaptive immune responses. In healthy individuals, the immunostimulants are play a role as proteolytic or promoter for formation of immune cell. Drugs which impart in production of immune cells are called Immunomodulator [4].

Immunosuppressant is structurally and functionally heterogeneous group of drugs which are often, simultaneously administered in a combination of Regiment to treat the various types of organ transplant rejection and autoimmune disease.

In clinical practice, both aspects of immunomodulation, i.e. immunostimulation and immunosuppression are equally important. Immunostimulation may require during conventional chemotherapy when the host defense mechanisms are to be activated under conditions of impaired immune responsiveness.

*Immunomodulator in Traditional Healthcare System DOI: http://dx.doi.org/10.5772/intechopen.94965*

The mechanism ofImmunomodulation activity occurs mainly via the stimulation of phagocytes, macrophages, lymphoid cells, increasing circulating total white cell counts and interleukin-2 levels. Immunological defense is a constant interplay between nonspecific and specific, cellular and humoral immune responses, stimulation and suppression of immunocompetent cells, and the influence of endocrine and other mechanisms. The Primary targets of the Immunostimulant are T or B lymphocytes and it plays a central role an immunostimulation. The second most important role in the stimulation of T lymphocytes is Activation of macrophages, which can be achieved either directly or indirectly, via macrophages [5].

## **6. Ayurveda system and immunomodulation**

The primary objective of Ayurveda, the Indian traditional system of medicine is the prevention of the disease. The different health care measures to be adopted by an individual are grouped together under the heading of "Rasayana." Rasayana meaning in sanskrit that literally implies to the circulation of rasa means Nutrients and these nutrients reach to the various parts of body, reaches upto tissues and cell. In that nutrients some are micro and macro nutrients which help in proper functioning of the body and resistant to diseases. Sushruta was more specific, describing a Rasayana as one, which is antiaging, increases the life-span, promotes intelligence and memory, and increases resistance to diseases [6].

## **7. Siddha system and immunomodulation**

The great Tamil saint 'Thiruvalluvar' has discuss the significance of diet as the cause of disease. According to Siddha system, the Term "Food is medicine and medicine is food" indicated that proper diet and healthy lifestyle containing medicinal herbs has intrinsic elements allowing the body to remain healthy. The ultimate essence of our consumed food acts as an essential component to strengthen the seven UdalkattugalSaaram (Plasma), Seneer(Blood), Oon (Muscles), Kozhuppu, Enbu, Moolai, Sukkilam, Suronitham thereby stimulating immunomodulation [6].

#### **8. Indian medicinal plant**

An in India wide range of traditional medicine that is from ancient time use for medicinal purpose. India is heritage for wide range of medicinal plants. These medicinal plants show various pharmacological action like anti-inflammatory, Anti diabetic, Antiulcer, Stimulant, Nervine tonic and many more.

In that some plants contain some micronutrients present in form of secondary metabolite and produce action of immunomodulation [7].

Some of the indigenous plants investigated for immunomodulatory effects.

#### **8.1 Garlic (***Allium sativam***)**

*Allium sativam* is also known as Lahsuna. It consists of bulb belonging to family. Liliaceae. It grows 1.5 to 2.5 cm with having Characteristic and Aromatic Odor.

Bulb are whit to pink in color. Garlic contain volatile oil, alliin and allicin.Garlic used as Carminative, expectorant, Antibacterial, disinfectant and also used in treatment ofpulmonary infection [7].

Immunomodulatory effect

## **8.2 Ghriti Kumari (***Aloe vera***)**

It consists of dried juice of leaves of *Aloe vera* belonging to family Liliaceae. Aloe is indigenous to eastern and southern Africa and grown in cape colony, Zanzibar and island of Socotra. In India it is available in almost all the houses. The genos Aloe consists of about 200 species, theseplants have rosettes of subulate, succulent large leaves. These leaves are sessile and have a strong spine at apex and also no. of spines in margins. Aloe mainly contains Barbaloin and alosin. Barbaloin is C- glycosides. Aloe used as a purgative, Antiseptic, cooling agent and also in many of the cosmetic preparation [7].

Immunomodulatory effect

## **8.3 Kalmegh (***Andrographis paniculate***)**

It consists of dried leaves and tender shoots of plant *Andrographis paniculate* belonging to family Acanthaceae. Kalmegh is an annual herb distributed in shri lanka and throughout india, specially in Maharashtra, Karnataka, Utter Pradesh, Tamilnadu, Andhra Pradesh and madhyapradesh. It is cultivated in some extent in Assam a west Bengal. Leaves are dark green, whit flowers and rose colored. It is odorless and intensely bitter in taste. It is used as Immunostimulant [7].

## **8.4 Shatavari (***Asparagus racemosus***)**

It is also called as Shatmuli. It consists of dried roots and the leaves of the plant *Asparagus racemosus* belonging to family Liliaceae. The roots are silver white or ash color externally and white internally. Spindle shaped and having slightly bitter followed by sweet taste. Shatavari roots is used as Galactagogue, tonic, diuretic. Shatavari I having ant oxytocic property. Shatavari also used as anti stress, Anticancer, Antiseptic, Antiaging and immunostimulant [8].

Immunomodulatory effect

## **8.5 Neem (Azadirectaindica)**

It is also known as Margosa. It is non edible fixed oil obtained from fully matured seeds of *Azadiractaindica* belonging to family Meliaceae.Neem plant found throughout India and other tropical countries. It mainly contains Glycerides saturated and unsaturated fatty acids. It having yellow colored oil with specific odor and bitter in taste. It contains Nimbin, nimbidin and other related compound possess antiviral activity. It is also used for making soap and manufacturing of oleic and steric acids. It also acts as pesticides and spermicides.

## **8.6 Amla (***Emblica officinalis***)**

Amla consist of dried and fresh of plant *Embellica officinalis* belonging to family Euphorbiaceae. It is small in size tree found in all deciduous forest in India. It is also found in Shrilanka and Myanmar. The Fruits are Green in color, after maturity it is converted into yellow and brick red. Having sore and astringent taste. It is used as a Antibacterial, Rejuvanate and it improve vitality.

Immunomodulatory effect

## **8.7 Tulsi (***Ocimum sanctum***)**

It is also called as Holy basil. Tulsi consists of fresh and dried leaves of plant *Ocimum sanctum* belonging to family Lamiaceae. It is herbaceous, branched, small herb annual plant found throughout India. The plant considered as sacred by Hindus. It is commonly cultivated in garden and grown in temples. It mainly contains volatile oil and eugenol is the main chemical constituent. Generally, all part of tulsi is used as a medicine.it act as an Anti-inflammatory, antiseptic, Antifungal, antiviral, Antiasthematic [10].

## **8.8 Haldi (***Curcuma longa***)**

I also known as Haridra, Indian Saffron, Turmeric, Curcuma.

Turmeric consist of dried and also fresh Rhizomes of plant *Curcuma longa* belonging to family Zingiberaceae. Externally it is having yellowish color with characteristic odor and bitter in taste. Curcumin is the main chemical constituents. It used as a spice, colorings agent, antiseptic, anti-inflammatory [11].

## **8.9 Ginseng (***Panax pesudoginseng***)**

It consist of dried roots 0f various species of Panax like P. *pesudoginseng, P. japonica, p.notoginseng.* Belonging to family Araliaceae. It is an important immunomodulatory drug. It generally used as health tonic and Adaptogen.

Immunomodulatory effect

It is also called Withania root, Winter cherry. Withania consists of dried roots and stem bases of *Withaniasomnifera* belonging to family Solanaceae*.*it mainly contain, Withaferin A, Withaferin, Anaferin, Withanolides. It acts as a Immunostimulant, Antirheumatic, Antistress [11].

Immunomodulatory effect

## **8.10 Kutki (***Picrorrhizakurroa***)**

*It used as* Immunostimulant and antioxidant. Immunomodulatory effect

*Murrayakoenigii* is commonly known as curry leaves, belonging to family Rutaceae. Because of its aromatic value mainly used as spice throughout India. Leaves are green in color. The bark, leaves and root are used as tonic, stomachache, stimulant and carminative Plant identified as Rsayanas in Indian ayurvedic system

#### *Alternative Medicine - Update*

of medicine have various pharmacological properties such as immunostimulant, tonic, neurostimulator, antiaging, antibacterial, antiviral, antirheumatic, anticancer, apoptogenic, ant stress.

Methanolic extract of *Murrayakoenigii* leaves gives cellular and humoral immune response [1].

## **8.11** *Tinosporacordifolia*

It is commonly called as Guduchi. It is large, glabrous, perennial, climbing shrub of weak and fleshy stem found throughout India. It is used as an antidiabetic, antipyretic, antimalarial, anti-inflammatory, hepatoprotectives, immunomodulatory, antispasmodic, antineoplastic activity.

### **8.12** *Bauhinia variegate linn*

The plant commonly found in moist waste ground and open plantations.it is cultivated throughout India. Its family is Caesalpiniaceae. The bark powder of plant is ingredients of the herbal tonic Kanchanar guggul,is an Ayurvedic remedy used to increases white blood cells. The plant also used as tonic for liver, in treatment of leprosy, menorrhagia, impurities of blood, wounds, ulcer, asthma.The effect of the ethanolic extract of the stem bark of *Bauhinia variegate* on the primary and secondary antibody responses was evaluated by the humoral antibody response for a specific immune response. Phagocytic cells, such as macrophages and neutrophils, barriers such as skin and a variety of antimicrobial compounds synthesized by the host, all play important roles in innate immunity [13].

### **8.13** *Abutilon indicumlinn*

*Abutilon indicumlinn* commonly known as Atibala, it is a stronger diuretic and heart tonic. It is also used for the remedy of the jaundice, piles, ulcer, leprosy, rakttapittadosha and blood purifier. The ethanolic extract of *Abutilon indicum* leaves beneficial for the treatment of impaired immunity.

#### **8.14** *Terminia arjuna Roxb*

It is commonly called as Arjuna bark and Arjun. It consists of dried stembark of the plant known as *Terminia Arjuna Roxb*. Belonging to family Combretaceae. It is common tree in Indian peninsula. Bark having Astringent taste. Bark is used as acardiotonic it also possesses diuretic and tonic properties. Diuretic properties are due to Arjunolic acid. The drug exhibit hypotension action with vasodilation and decrease heart rate [13].

## **9. Conclusion**

Besides of allopathic diagnosis system, we can use Traditional system for the treatment of various diseases and which can be affordable to the common communities. Ayurveda and siddha system involved the medicinal plants for the treatment of diagnosis and it is available easily in Indian forest. So, the medicinal plant or Indian traditional system is best way for treatment or Immunomodulator.

*Immunomodulator in Traditional Healthcare System DOI: http://dx.doi.org/10.5772/intechopen.94965*

## **Author details**

Shweta Saboo Government College of Pharmacy, Karad, India

\*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.

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**3.4 E-research – E-design methodology**

Because the research activities are carried out in teams and because researchers are located in different places, there is a clear need for a precise methodology for communication research. These are supported by the TEAM CENTER software.

The stages of a research methodology are:

clear description of the problem;

The trend in terms of research and design centres is international cooperation and collaboration. These can be achieved by organizing virtual research and design centres.

The development of communications and computer technologies (ICT) offers the possibility of using the Internet in research design activities (E-design E-research), within virtual

Identification of the general objectives should only be made by taking into account the

Whenever goals are set for shorter terms, their planning can be achieved with better

 The organization of resources is much more efficient due to the wider access to human resources. Physical attendance is unnecessary, user on-line connectivity is sufficient; The realization phase in the virtual research centres is performed much faster due to

 The research results can better meet the initial needs because of on-line prototyping. Whenever the prototype development indicates a deviation from the proposed

 Cooperation in solving problems or discussions in the study group can be achieved through the forum or chat, virtual communities, international scientific collaboration

The major objective of the future research/design centres has to be the improvement in the

Future research-design centres can be viewed as appropriate mechanisms to establish links with world research, as well as to prevent the need for researchers to work "behind the walls". This could be a solution to stop the migration of researchers in countries who have a

A proposal for organizing a research-design activity within the virtual research-design centres was put forward in the domain of mechanical engineering and, more specifically, in

Because the research activities are carried out in teams and because researchers are located in different places, there is a clear need for a precise methodology for communication

Virtual events can take place in the virtual centre, in a chat room, or a forum;

**3.3 Trends in design-research centres**

greater information transfer speed;

Advice can be provided via email, chat;

**3.4 E-research – E-design methodology**

The stages of a research methodology are:

clear description of the problem;

via Web/Internet;

objectives, corrective action can be undertaken.

The system allows shared editing of documents.

performance of the centre for international exchange of knowledge.

the field of cutting tools, by using the E-creative design concept.

research. These are supported by the TEAM CENTER software.

much higher technological development of information and communication.

Virtual research combines a variety of activities, as follows:

Information retrieval is eased by the search capabilities of the platform;

centres (Kincheloe, 2006).

world trends;

accuracy;

The Industrial Engineering department from "Lucian Blaga" University of Sibiu did a research design platform focused on creativity. The main theoretical and practical issues of the research activity performed on this platform are presented below. For an easier understanding, an example was used.


Modeling of Creep Deformation and Creep Fracture

Qiang Xu and Zhongyu Lu

### Abstract

This chapter reports the recent progresses in (1) the development of a modified hyperbolic sine law able to depict the minimum creep strain rate over a wider range of stress levels; (2) the development of the creep fracture criterion and model based on the cavity area fraction along grain boundary calibrated with the most representative and comprehensive cavitation data obtained from X-ray synchrotron investigation; and (3) the development of mesoscopic composite approach modeling of creep deformation and creep damage. The first progress facilitates to overcome the difficulty in creep deformation modeling caused by stress breakdown phenomenon; the second progress is of a really scientifically sound and fundamental new approach, first in the world; the third progress provides the concept and tool, at the appropriate size scale, for the modeling of the creep deformation and creep fracture. They all contribute to the specific knowledge and new methodology to the topic area. Furthermore, it is expected that cavitation fracture modeling methodology reported here will find use in the analysis and modeling of other types of failure such as ductile and fatigue failure. This chapter presents an excellent example of interdisciplinary collaborative research and it advocates further such collaboration in its conclusion.

Keywords: creep stress breakdown, creep strain and stress law, Xu's modified hyperbolic sine law, creep cavitation damage and fracture model, X-ray synchrotron cavitation; mesoscopic composite type modeling

#### 1. Introduction

#### 1.1 General

Creep damage is one of the life-limiting factors for high-temperature components. A sound scientific understanding and an accurate mathematical description of the creep deformation and creep fracture are of great interest to and a challenge for the materials and structural integrity research communities and hightemperature industries.

It is generally understood and accepted that for the majority of metals and alloys, creep cavitation at grain boundary is the cause for the creep fracture [1, 2].

Creep continuum damage mechanics (CDM) has been developed to model creep deformation and creep fracture, where internal variables were introduced to depict the macroscopic behavior and the cavitation is incorporated in an average, smearedout manner.

High Cr alloys is one of the alloys developed for and utilized in power generation industry. So, they have been chosen for the research, and progress made with them will be reported here. Additionally, copper-antimony alloy is used in the illustrative example of the mesoscopic composite modeling of creep deformation and fracture due to the unavailability of the micro-mechanical constitutive equation for high Cr alloys. Although the examples of progress reported here are based on the specific material, the methodology is generic and not material dependent.

#### 1.2 The problem

In the development of and particularly in the characterization of hightemperature structural materials, the accelerated creep testing (short-term) may be conducted; then the result might be extrapolated for long-term service condition (say 100,000 hours). Normally, this approach is not reliable, as this microstructure may progressively degrade with often unexpected consequences for long-term creep performance under lower applied stress. Such phenomenon is called stress breakdown; it profoundly exists in high Cr alloys [3–7].

Ennis et al. [3] found that the Norton stress exponent n was found to be 16 for the stresses of above 150 MPa at 600°C and above 110 MPa for 650°C, and an n value was 6 below these stresses. A selection of quantitative presentation of the dependence of the minimum creep strain rate, creep lifetime, and strain at failure on the stress level can be found in [3]. Furthermore, Lee et al. [4] found (1) the stress exponent for rupture life to be decreased from 17 in short-term creep to 8 in long-term creep for the ASTM grade 92 steel crept at 550–650°C for up to 63,151 h, (2) the change of fracture mechanisms with stress level, and (3) creep cavities nucleated at coarse precipitates of Laves phase along grain boundaries.

It can be seen that (1) a wider range of stresses, particularly the lower stress level, must be considered; (2) there is a change of creep deformation mechanism and possible creep damage mechanism under the different stress level. Currently, there is no adequate and accurate data to characterize the creep cavity nucleation, growth, and coalescence under lower stress.

#### 1.3 Current creep cavity damage modeling

In an attempt to model the long-term creep behavior, Yin et al. [8] have proposed a phenomenological relationship between the creep cavity damage and creep strain, which departed from the firm and well-known mechanism-based relationship of Dyson [9]. The relevant equations are listed below for completeness:

Dyson [9]:

$$
\dot{D}\_n = \frac{k\_N}{\varepsilon\_{f\_u}} \dot{\varepsilon} \tag{1}
$$

Yin et al. [8]:

$$
\dot{D}\_n = A \epsilon^{\beta'} \dot{\epsilon} \tag{2}
$$

where A is the creep cavity damage coefficient, and it is assumed that it does not change with stress, it changes with temperature.

Yin's approach cannot be extrapolated into a lower stress level than it has been calibrated according to Yang et al. [10] as a constant value of A is not able to depict the stress breakdown phenomenon.

Modeling of Creep Deformation and Creep Fracture DOI: http://dx.doi.org/10.5772/intechopen.89009

Basirat et al. followed Yin's approach but allowed the cavity damage coefficient to be stress level dependent, in the following form [11]:

$$
\dot{D}\_n = A \dot{e} e^{0.9} \tag{3}
$$

However, an unexpected abnormal variation of the value of A with stress level occurred which is shown in Table 1 and graphically in Figure 1 [12]. Due to the lack of a trend with stress level, it is hard to use them in prediction with confidence. The concept of creep cavity damage coefficient to be stress level dependent had been introduced by the first author in 2003 [13] for low Cr alloy creep damage modeling where no such abnormality occurred.

Hence, the phenomenological modeling of creep cavity damage for high Cr alloy is not satisfactory.

Furthermore, the methodology, based on the isochronous surface concept only, for the generalization of a set of uniaxial creep damage constitutive equations into a set of multiaxial version is conceptually flawed [14–16]. Though the creep deformation consistence has to be included, this has not been very well appreciated by the majority of research community, even in the published review type of articles. Progress can be found only in very limited publications, for example, the original one [16, 17] and the more recent one [18].

#### 1.4 Opportunity and research progress

Table 1. The variation of cavitation coefficient A [11].

Figure 1. The variation of creep cavity damage coefficient A with different stress and temperature [12].

In 2013, the first author noted that the available creep cavitation data is produced with X-ray synchrotron technique by materials scientists. The X-ray synchrotron is a very advanced technique, and it is able to produce a detail and un-destructive, hence more presentative, information over a small volume. This is a very significant advance for the characterization of creep cavitation. Hence, it was the author' view [19] that such information about cavitation should be very valuable for the modeling of creep cavity damage and fracture. Such breakthrough in modeling of creep cavity damage and fracture will be reported with selected examples.

3.The mesoscopic composite approach modeling of creep deformation and damage

Furthermore, the authors [15] have observed that that the current creep continuum damage mechanics operates at macroscopic level is of phenomenological suffering an ambiguity in the depicting of the creep deformation and creep cavity damage and fracture [15], hence, concluded that a mesoscopic composite approach modeling is necessary and better. In this new approach, the grain and grain boundary will be separately presented in space and in property (constitutive equations) to specifically reflect the creep deformation processes and creep damage processes and the ultimate creep fracture. The initial progress will be reported in this chapter.

4.This chapter ends with discussion, conclusion, and suggestion for future work which advocates closer interdisciplinary collaboration.


**2. Literature review**

#### **2.1 Quaternary systems with two aliphatic compounds**

Up to now, a quite wide range of papers dealing with liquid-liquid equilibrium data of hydrocarbon + aromatic + IL ternary systems can be found in literature. These studies are essential to determine the capability of ILs to extract aromatic compounds; however, many other compounds are present in refinery streams, and these compounds can modify the extraction process.

With the aim of analysing the influence of more than one aliphatic compound on the extraction of aromatics, liquid-liquid equilibrium data of several quaternary systems have been published [9–14].

Requejo et al. [9–11] studied the extraction of benzene from its mixtures with octane and decane using tributylmethylammonium bis(trifluoromethylsulfonyl) imide, [N4441][NTf2]; 1-butyl-1-methylpyrrolidinium dicyanamide, [BMpyr] [DCA]; and 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide, [BMpyr][NTf2], and the results of the quaternary system were compared with those obtained for the ternary systems octane + benzene + IL and decane + benzene + IL.

Using [N4441] [NTf2], the highest values of β were obtained for the ternary system octane + benzene + [N4441] [NTf2], while the β values calculated for the

**69**

*Extraction of Aromatic Compounds from Their Mixtures with Alkanes: From Ternary…*

consequently the presence of two alkanes does not seem to affect them [9]. Solute distribution coefficient is similar for both ternary systems octane + benzene + [BMpyr][DCA] and decane + benzene + [BMpyr][DCA] and for the quaternary system octane + decane + benzene + [BMpyr][DCA], while the selectivity for the quaternary system is lower than for the ternary system with decane and

ternary system decane + benzene + [N4441][NTf2] and for the quaternary system are similar. Selectivity values are quite similar for the ternary and quaternary systems;

A different influence was found comparing the ternary systems octane + benzene + [BMpyr][NTf2] and decane + benzene + [BMpyr][NTf2] with the quaternary system decane + octane (1) + benzene (2) + [BMpyr][NTf2] [11]. In that case, both solute distribution coefficients and selectivity are lower for the quaternary system. The extraction of toluene from its mixtures with heptane and cyclohexane, using ethyl-methylimidazolium-based ILs, was studied by Corderí et al. [12–14]. The selected anions were methylsulphate [MSO4], acetate [OAc] and dicyanamide [N(CN)2]. According to their results, solute distribution coefficient clearly follows the trend:

With regard to selectivity, higher values were obtained with [EMim][N(CN)2]. Comparing quaternary systems with the respective ternary ones, the following

i.Solute distribution coefficients for the ternary systems with [EMim][MSO4] are quite similar and higher than those obtained for the quaternary system at higher toluene composition in the hydrocarbon-rich phase. When the toluene concentration in the hydrocarbon-rich phase is lower than 0.2, similar values of β were obtained for the ternary and the quaternary systems.

ii.In the case of [EMim][OAc], β values for the quaternary system are slightly higher than those obtained for the ternary systems independent of the

iii.Similar β values were obtained for the ternary and quaternary systems using

iv.In all cases, selectivity values for the quaternary system are between the

As it can be seen, both solute distribution coefficients and selectivity values can be influenced by the presence of another hydrocarbon in different ways. The lack of more experimental data does not allow us to take general conclusions about the influence of other aliphatic compounds present in the mixture; consequently more

Among all the ILs that have been studied as separation agents, only a small number

of them have shown simultaneously solute distribution coefficients and selectivity higher than sulfolane since, generally, high selectivities are related to low solute distribution coefficients and vice versa. On the other hand, most ILs present quite high viscosity, which make their use difficult in extraction processes. The proper selection of two ILs could lead to a separation agent, whose physical properties and extraction performance overcome those of sulfolane. Therefore, some pairs of ILs have been tested to extract aromatics, mainly benzene or toluene, from their mixtures with alkanes.

*DOI: http://dx.doi.org/10.5772/intechopen.86229*

higher than for the ternary system with octane [10].

[EMim][N(CN)2] > [EMim][OAc] > [EMim][MSO4].

toluene concentration in the hydrocarbon-rich phase.

**2.2 Quaternary systems with IL mixtures as extraction agents**

results were obtained:

[EMim][N(CN)2].

values of the ternary systems.

experimental data would be necessary.

## *Extraction of Aromatic Compounds from Their Mixtures with Alkanes: From Ternary… DOI: http://dx.doi.org/10.5772/intechopen.86229*

ternary system decane + benzene + [N4441][NTf2] and for the quaternary system are similar. Selectivity values are quite similar for the ternary and quaternary systems; consequently the presence of two alkanes does not seem to affect them [9].

Solute distribution coefficient is similar for both ternary systems octane + benzene + [BMpyr][DCA] and decane + benzene + [BMpyr][DCA] and for the quaternary system octane + decane + benzene + [BMpyr][DCA], while the selectivity for the quaternary system is lower than for the ternary system with decane and higher than for the ternary system with octane [10].

A different influence was found comparing the ternary systems octane + benzene + [BMpyr][NTf2] and decane + benzene + [BMpyr][NTf2] with the quaternary system decane + octane (1) + benzene (2) + [BMpyr][NTf2] [11]. In that case, both solute distribution coefficients and selectivity are lower for the quaternary system.

The extraction of toluene from its mixtures with heptane and cyclohexane, using ethyl-methylimidazolium-based ILs, was studied by Corderí et al. [12–14]. The selected anions were methylsulphate [MSO4], acetate [OAc] and dicyanamide [N(CN)2]. According to their results, solute distribution coefficient clearly follows the trend:

[EMim][N(CN)2] > [EMim][OAc] > [EMim][MSO4].

With regard to selectivity, higher values were obtained with [EMim][N(CN)2]. Comparing quaternary systems with the respective ternary ones, the following results were obtained:

As it can be seen, both solute distribution coefficients and selectivity values can be influenced by the presence of another hydrocarbon in different ways. The lack of more experimental data does not allow us to take general conclusions about the influence of other aliphatic compounds present in the mixture; consequently more experimental data would be necessary.


**5.1 Top-down involvement of higher-order processes in happiness genesis**

The sustainable happiness model suggests that events are the factor associated with the smaller influence on happiness level [13, 22]. Intentional activity (*i.e.,* actions requiring some degree of effort) including cognitive activity would better account for

### **Figure 2.**

*Definitions of happiness found in studies dealing with higher-order processes involved in happiness.*

### *Enacting Happiness from Emotions and Moods DOI: http://dx.doi.org/10.5772/intechopen.106954*

happiness variation than would circumstances [13, 22]. Happiness would be generated in a top-down manner and be a result of higher-order processes.

Events favoring happiness do not systematically lead to be happy [108]. First, La Rochefoucauld (1694/1930) wrote "happiness does not consist in things themselves but in the relish, we have of them" (p. 51; [108]). This philosophical statement is supported by the theoretical background of cognitive behavioral therapy. Situations and events do not have a valence and do not elicit positive or negative emotions *per se*. Rather, it is the cognitive interpretation of the event that elicits positive or negative emotions. Such a statement is also supported by the construal approach to happiness [109]. This top-down theory of happiness suggests that an objective event is interpretated subjectively. Cognitive processes shape the effect of events on happiness. Each individual builds their own reality, which determines specific hedonic outcomes, leading in turn to various levels of happiness. Second, individuals have to be able to perceive happiness-favoring events. Sad mood and anhedonia are core symptoms of major depressive disorder [110]. These symptoms seem to be the opposite of the effective component of happiness in the hedonic theory of happiness. Generally, individuals suffering from depressive disorder are attracted by negative information and avoid positive information [111, 112]. The incapacity to perceive events favoring happiness (also called "anhedonic bias") could contribute to the incapacity to experience positive affects [111].

Taken together, these data suggest that happiness is the result of higher-order processes in a top-down manner before, during, and after the event. Before the event, higher-order processes can help to detect events favoring happiness. During and after the event, higher-order processes participate in the interpretation of the situation. Higher-order processes can also help to reinterpret an event in a positive manner and elicit happiness. Happy individuals would perceive, evaluate, and think a same event as more positive than unhappy individuals [109]. This section aims to provide a brief critical review of higher processes' top-down influence on happiness. First, we examine how cognitive style participates in the happiness genesis. Following this, we summarize evidence showing that "executive functioning" plays a substantial role in happiness generation. Finally, we report that metacognitive processes also significantly contribute to happiness.

### **5.2 Cognitive styles**

Information processing styles are associated with mood variations. We review three information processing styles involved in happiness development: the use of probability, global-local processing, and attributional style.

According to the decision affect theory, the expected value of an outcome influences the emotional experience elicited by this outcome [113, 114]. The estimated likelihood to obtain a better alternative is a determinant of happiness derived from an event. We can suppose that winning \$500 in a lottery is a happiness-favoring event. But felt happiness will certainly be lower if it is more likely to win \$5000 than \$500. Conversely, felt happiness will certainly be higher if it is more likely to win \$50 than \$500. The outcome is the same but the felt happiness is different. Children (> 4 years old) and adults inferred more happiness when the likelihood to obtain a better outcome was low rather than high [115]. Outcomes obtained could compare with a standard established from the use of probability [115]. Satisfaction would result from an outcome evaluation through a comparison process [116]. If a positive outcome is highly likely, then a high standard is established. Happiness and hedonic

load of events decrease when the outcome does not reach the expected standard. Use of probability, as a higher-order process, seems to be in happiness genesis. Especially, the use of probability has an influence on the hedonic load of a happiness-favoring event in establishing an expected outcome. Happiness genesis seems to be conditioned in a top-down manner under the influence of this expectation.

It has been often demonstrated that negative mood was associated with local information processing, whereas positive mood was often associated with global processing of information. Ji et al. (2019) have manipulated the style of perceptual processing (global *vs.* local) to investigate its role in happiness genesis. Through four experiments, this study showed that global processing leads to be happier and in a better mood than local processing [117]. Global processing would be associated with a big picture schema leading to a global perspective. Global perspective would increase the likelihood to detect a positive stimulus and would increase the likelihood to experience positive emotion. Furthermore, global processing would be associated with a more abstracting interpretation of life, regardless of current and minor worries. To summarize, global processing increases happiness level by two hypothetical top-down mechanisms: a) an expansion of attentional focus increasing the likelihood to detect positive stimuli and experience positive emotion (affective subjective well-being); b) a global view of life in which minor concerns are less salient, increasing life satisfaction (cognitive subjective well-being).

Following an event, individuals can process this event either by relating the cause to the self (internal style) or by relating the cause to an external factor to the self (external style). The style adopted is different according to mood variation and event valence. For example, internal style for negative events is a strong predictor of depressive disorder (*e.g.,* [118]). Empirical findings show that the way we attribute cause (internally or externally) of an event (positive or negative) is a determinant of happiness. Internal attributions for negative events are associated with an increase in anhedonia severity in turn associated with a decrease in happiness [119]. There is a direct negative correlation between the level of happiness and the internal attribution of negative events [119]. Internal attribution and "stable" attribution (*i.e.,* judge an event with a high likelihood to occur again) for positive events increase happiness [120]. An attributional style for negative events, in which causes are processed as less personal, less permanent, and less pervasive, improves happiness. The way we process events in term of self-involvement contributes to explaining the genesis of happiness in a top-down manner. Attributional style would be associated with personality. Extravert personality would be associated with an internal attributional style for positive events. Neurotic personality would be associated with an internal attributional style for negative events [120]. Personality influences the attributional style. The latter could in turn determine the experience of happiness in a descendant way. Lyubormisky (2001) searched for a mechanism that could explain the relationship between extraverts/neurotics and happiness/unhappiness, respectively. The attributional style could explain such a relationship. If extravert people attribute the causes of positive event to themselves, then they are more inclined to be sensitive to reward, experience positive effect, and be happy (Lyubormisky, 2001). If neurotics people attribute the causes of negative event to themselves, then they are more inclined to be sensitive to punishment, experience negative affect, and be unhappy [109].

Taken together, these findings reveal that happiness is determined in a top-down manner by the way the information is processed. Information processing seems itself associated with personality and cognitive schema. Such findings suggest that "executive functions" could be a determinant of happiness. As exposed above,

global-local processing has been hypothetically associated with attentional focus [117]. Attributional style is associated with "executive functions." Cognitive flexibility and inhibition (important processes related to "executive functions") are associated with internal attributions for positive events and "stable" attributions for negative events [121].

### **5.3 Executive processes**

Depressive disorder seems to be the opposite of happiness, especially when considering depressed mood and anhedonia, which have been considered as core symptoms of depression [110]. Cognitive dysfunctions in depressive disorder support the importance of "executive functioning" in happiness. Some "executive functions" are impaired in this mood disorder [122]. Such impairments could explain the difficulty to experience positive emotion and happiness. Impairment of top-down cognitive control (the set of "executive functions" that flexibly produce goal-directed thoughts and behaviors) could be involved in negativity bias (*i.e.,* the tendency to be attracted by negative stimuli and the interpretation of neutral stimuli as negative). Inhibition and working memory difficulties would impair both the inhibition of negative representations and their update (shift from negative representations to positive ones) [122].

Happiness derived from subjective well-being could emerge from "executive functioning" [123]. Working memory is involved in subjective well-being [124]. People who are better at maintaining and updating (*i.e.,* modifying representation in working memory according to new information) positive stimuli in working memory are happiest [124]. That is they have a higher life satisfaction level (cognitive subjective well-being) and experience more positive emotion than negative emotion (affective subjective well-being). Happiness could emerge from the update of positive information. Update leads to a repetitive activation of positive information in working memory. It would be easier to access positive information and process them, leading to more positive thought eliciting happiness [124]. Concerning the cognitive component of subjective well-being, life satisfaction is associated with goal achievement. "Executive functioning" is involved in goal achievement, for example through strategic planning. Therefore, they support goal achievement, which would be a condition of happiness [123]. Although goal achievement seems to be central to happiness genesis, goal must be realistic and flexible. Sometimes, reaching happiness is an objective *per se*. However, if expected happiness is extreme (*e.g.,* individuals believe that experiencing happiness is a routine, value experience only if it generates happiness, think that there is something problematic if they do not experience happiness) and people believe that they cannot modify their emotional states, then happiness decreases [125]. This finding highlights the need for mental flexibility and the detrimental effect of rigid and unrealistic goals on happiness. "Executive functioning" could be involved in the psychological well-being component [123]. Eudaimonic pursuit of happiness involves self-control to inhibit and delay immediate reward while staying focused on higher-order goals. Working memory allows considering several action pathways to reach the goal [123].

Goal achievement seems to be very important in happiness because it is involved in psychological well-being and cognitive subjective well-being. However, there are sometimes conflicts between short-term goals leading to immediate but smaller rewards and long-term goals leading to delayed but larger benefits [126]. Such conflicts are also called self-control conflicts [126]. Self-control, notably through

"executive functioning", would be involved when resolving this conflict [126, 127]. When individuals are motivated to pursue affective subjective well-being by imaging a pleasure-eliciting event during inhibition tasks, they activate an interfering short-term goal. Consequently, inhibition performance decreases. Self-control conflict would also involve working memory to maintain an active representation of the long-term goal [126]. Cognitive control (*i.e.,* the set of "executive functions" involved in flexibly producing goal-directed thoughts and behaviors) plays a role in meeting goals while managing conflicting pleasure-favoring distractors [60]. Cognitive control may be divided into proactive control, retroactive control, and evaluative control components. Proactive control allows guiding behavior with a strategy in order to achieve a long-term goal and positive life event. Retroactive control focuses attention toward a reward-eliciting stimulus. Evaluative control consists of monitoring and assessing outcomes of behaviors. Executive control seems important to protect long-term goals leading to happiness and to resolve self-control conflicts. Wiese et al. (2018) showed that self-control predicted subjective wellbeing. Self-control produces succeeding and thriving, leading themselves to happiness [123]. These long-term benefits preserve happiness because they counterbalance the inhibition of immediate pleasure. Flexibility remains important to prevent unrealistic goals that promote unhappiness. Sometimes, individuals try to stay focused on long-term goals, while enjoying present moment pleasure, to reach happiness. In this kind of situation, top-down control can contribute to reducing dissonance between immediate reward and long-term goal [123].

Executive control of selective attention seems to be a main determinant of happiness. Focusing attention on present information would promote happiness [60]. This process is associated with mental flexibility, which promotes the ability to shift attentional focus, notably on rewarding events and new opportunities [60]. Cognitive control (notably working memory, flexibility, and inhibition) has neural correlates in the executive control network [128]. Activity in executive control network is associated with subjective well-being [128]. Evidence arising from aging research supports these statements. Happiness and emotional regulation could be enhanced with aging [60]. Such an enhancement is sometimes explained by various age-related changes in cognitive processing (*e.g.,* selective attention focused more on positive information than on negative information). Such modifications of cognitive processes could consist in increased focusing on positive information in the elderly [60]. At the neurobiological level, the recruitment of prefrontal cortex is correlated with the modification of cognitive processes that enhance happiness in aging [60]. This cerebral region is included in executive control network allowing cognitive control and is associated with happiness ([128]; see also the previous section for the involvement of prefrontal cortex in top-down genesis of happiness). The role of attentional focus control is also supported by studies on rumination, mind-wandering, and dwelling. Dwelling and rumination are circular and repetitive self-reflection characterized by intrusive thoughts, images, and memories [129]. Self-reflection is negatively associated with happiness [130]. The decrease in happiness related to rumination could be explained by impairment in "executive functioning." Self-reflection could cause an interference effect [129], monopolize and drain cognitive resources used in executive process [109, 129]. Cognitive resources would be no longer available to control attention, focus on positive stimuli, achieve goal, and solve problems through executive processes. Self-reflection could divert attentional focus from happiness-favoring events and cognitive resources would no longer be available to correct attention focus (*e.g.,* through inhibition or mental flexibility). Self-reflection induced by dwelling or

*Enacting Happiness from Emotions and Moods DOI: http://dx.doi.org/10.5772/intechopen.106954*

rumination is associated with the default-mode network including medial prefrontal cortex, posterior cingulate cortex, and inferior parietal lobule [96, 97, 128]. The previous section has shown that this cerebral network has a central role in happiness experience notably in relation to self-reflection [97, 128]. The default-mode network disturbs top-down executive processes involved in happiness.

"Executive functioning," notably through cognitive control, including inhibition, mental flexibility, working memory, and selective attention, has an important role in happiness. Especially, intentions, goals, and expectations would induce a synchronization of "executive functioning" to realize plans and reach happiness in a top-down manner. Furthermore, individuals could try to apply some strategies to modify "executive functioning" (*e.g.,* in the case of rumination, dwelling, and mindwandering) and enhance happiness. Metacognitive processes could be determinants of happiness. They also reinforce evidence in favor of the processes exposed above.

### **5.4 Metacognitive emotion regulation**

We have reported that cognitive style and "executive functioning" are determinants of happiness. Individuals can use metacognitive strategies to change these cognitive processes in order to enhance happiness and alleviate negative affect. Metacognitive strategies employed to regulate emotion (*i.e.,* efforts to modify emotional response [130]) can be considered higher-order determinants of happiness.

Cognitive reappraisal is a metacognitive strategy involved in happiness genesis. It contributes to modifying the interpretation of an event, by proposing a new meaning. Therefore, it allows reinterpreting a situation as being source of pleasure in a top-down manner. This new perception of the pleasant activity increases subjective well-being [130]. Cognitive reappraisal can be used to produce a more optimistic interpretation of future, which increases the experience of positive emotion. Cognitive reappraisal is also useful to reassess the attributional style, which influences happiness [108]. We have discussed above the top-down involvement of attributional style in happiness. Individuals could also reappraise the perceived value of a situation: they experience more positive affect for things with higher value [108]. Cognitive reappraisal involvement in happiness is supported by mindfulness-based cognitive therapy (MBCT). MBCT practice increases the level of happiness (psychological and subjective well-being; [131]). MBCT practice would broaden the identification of experiences enhancing life satisfaction (cognitive subjective well-being). Cognitive reappraisal would allow reevaluating experience as positive, which increases the experience of positive emotion (affective subjective well-being; [131]). The improvement of eudaimonic well-being is explained by the enhancement of subjective well-being that is associated with the meaning of life. This study also suggests the involvement of attentional processes to broaden the attentional focus that identifies events [131].

Attentional deployment (*i.e.,* the way individuals direct their attention; [108]) can be related to metacognitive emotional regulation strategies that influence happiness too. Attentional deployment could increase the experience of positive emotion and happiness by mentally simulating positive events and increasing the saliency of present moments and positive autobiographical memories [108]. Exercises derived from positive psychology suggest that reporting early and recent autobiographical memories increases happiness [132]. Such "positive" exercises could be underpinned by attentional deployment strategy. Mindfulness, including the focus of attention on the present moment, would improve cognitive control and contribute to alter the

default-mode network. The decrease in the activity of the default-mode network associated with mindfulness could explain the attenuation of rumination [96]. Considering, the negative relationship between rumination and happiness, the attenuation of rumination associated with mindfulness could increase happiness.

Cognitive reappraisal and attentional deployment are also both metacognitive strategies that could participate in enhancing self-control and increasing happiness. For example, attentional deployment may serve to avoid immediate temptation and stay focused on long-term goals [133].

Cognitive reappraisal and attentional deployment are both top-down determinants of happiness. They play a critical role in influencing cognitive processes toward enhancing happiness.

### **5.5 Discussion**

The goal of this section was to provide a brief critical review of higher-order processes as top-down influencers of happiness. We have reported findings supporting the top-down influence of several higher-order processes (*e.g.,* cognitive style, cognitive control and "executive functions" and metacognitive strategies) over happiness. At this point of our review, we propose to distinguish between two levels of top-down processes involved in happiness dynamics (**Figure 3**). The first level includes cognitive style (*e.g.,* use of probability, Global-Local processing, attributional style) and "executive functioning." The second level of higher-order processes is represented by metacognition, personality, intentions, and goals influencing cognitive processes belonging to the first level of higher-order processes.

Critically, although some experiments have manipulated factors that could influence happiness, numerous other studies are"correlational" in nature. Even when top-down influence could be involved, the influence of bottom-up processes on higher-order processes cannot be excluded. Sometimes, it is difficult to know what is the cause and what is the consequence [109]. A novel pathway of happiness genesis based on a bidirectional influence from bottom-up and top-down processes should be carefully considered.

**Figure 3.** *Top-down pathway leading to happiness.*


**Author details**

```
Ali Mohammadi1
               * and Anthony Anukam2
```
1 Department of Engineering and Chemical Sciences, Karlstad University, Karlstad, Sweden

2 Biochemical Process Engineering, Division of Chemical Engineering, Department of Civil, Environmental and Natural Resources Engineering, Luleå University of Technology, Sweden

\*Address all correspondence to<EMAIL_ADDRESS>
© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

*The Technical Challenges of the Gasification Technologies Currently in Use and Ways… DOI: http://dx.doi.org/10.5772/intechopen.102593*


**Author details**

Weixia Zhong and Nissar A. Darmani\*

\*Address all correspondence to<EMAIL_ADDRESS>
Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA, USA


**Abstract**

The fetal blood flow in two arteries and one vein of the human umbilical cord could be influenced by the conditions of the fetal growth and placenta that the evaluation of the blood flow pattern by ultrasound Doppler velocimetry is important. That is, the mechanical environment in the umbilical cord should be kept to maintain the blood flow suitable for good fetus growth. In this chapter, a human umbilical cord model for finite analysis, based on the mechanical and histological characteristics is proposed. Considering that the active force production by hyaluronan, proteoglycan, smooth muscle cells, and myofibroblasts could influence the mechanical environment in the umbilical cord, the computation with the proposed model was carried out in order to evaluate the influence. The changes in the mechanical environment caused by the active force production and their influences on the fetal blood flow through the pressure rise and drop in the arteries of the umbilical cord are introduced.

**Keywords:** human umbilical cord, artery, vein, Wharton's jelly, hyaluronan, proteoglycan, smooth muscle cell, myofibroblast, active force production

## **1. Introduction**

The human umbilical cord, connecting the fetus and placenta, conveys fetus blood through two arteries and one vein [1]. While the umbilical cord itself spirals, the artery is accompanying the vein with spirals. The blood flow in the umbilical artery and vein, which ultrasound Doppler velocimetry is generally used to measure, shows different characteristics in pulsation: the artery has pulsation, but the vein, except the regions around the ductus venosus and portal vein, does not [2–6]. The difference in pulsation between the artery and vein has been also indicated by pressure [7]. The blood flow pattern could be influenced by the condition of fetal and placenta so that analyses of the flow pattern would be helpful for diagnosis. For example, the pulsation pattern of the blood flow in the artery and vein around the ductus venous and portal vein have been analyzed in pathological aspects [2–6]. In the meantime, the sizes of the umbilical cord, artery, and vein have been reported with some variation [8–14].

Considering the size of the umbilical cord at 40 weeks of gestational age, the diameters of cord, artery, and vein in Ref. [8], whose number of cases was larger than those in [9–14], was 17.8 mm, 4.6 mm, and 9.1 mm at average, respectively, while the length of the cord was more than 50 cm [1]. That is, the blood should travel a long way more than 50 times of the diameter. The distension of the artery and vein of the umbilical cord [15] would contribute to keeping the proper blood flow patterns in the artery and vein, necessary for fetal growth. In numerical analyses, the influence of the umbilical cord's coiling [16] and pressure drop [17] on the blood flow in the artery and vein, and that of arterial pressure pulse on the flow in the vein [18] have been reported. The mechanical environment in the umbilical cord would be arranged as keeping the shapes of the blood vessels, but the investigation has been barely carried out.

The human umbilical artery and vein show the characteristics different from major blood vessels in the body, including large and active endothelial layers [1, 19]. Moreover, the artery has shown two distinctive smooth muscle layers: inner layer, loosely arranged cells with abundant ground substance; outer layer, circularly arranged cells [20]. While myosin and vimentin have been found in both two layers, only the outer layer has indicated desmin [21]. These two blood vessels are covered with Wharton's jelly, whose college fiber has shown the network with canalicular-like structure, and cavernous and perivascular spaces (stromal cleft), which would be helpful for diffusion [22, 23]. Considering the control of the mechanical environment in the umbilical cord, it has been pointed out the contribution of hyaluronan and proteoglycan to pressure control [24], and myofibroblasts, which show active contraction [25, 26].

The mechanical properties of the human umbilical cord and blood vessels have been reported [27–29]. Considering the limitation of the range of the blood pressure in the arteries and vein [7], and nonlinearity in the stress-strain relationship [27–29], the elasticity in the limited range would be proper to estimate the mechanical environment in the umbilical cord. Given that the stress distribution at blood vessel walls would be homogeneous at physiological pressures [30], the assumption that the stress distributions at the umbilical artery and vein would be homogeneous at the average pressure could be made.

In this chapter, a computational model of the human umbilical cord is proposed in order to estimate the mechanical environment. Influence of the change in blood pressure, active force production in smooth muscle cells, myofibroblasts, hyaluronan, and proteoglycan on the mechanical environment and its relation to the fetus's blood flow is shown.

#### **2. Computational model of the human umbilical cord**

The computational model of the human umbilical cord has been developed on the finite element analysis (FEA) software, COMSOL Multiphysics® ver.6 (COMSOL, Inc. MA). The length of the umbilical cord is longer than 50 times of its diameter so that the cross section, whose normal vector was the axial direction of the umbilical cord, was modeled and analyzed as the representative of the umbilical cord. The analysis has been carried out two-dimensionally, as a plane strain problem.

#### **2.1 Spatial arrangement and constraint**

The spatial arrangement and size of each component are shown in **Figure 1** and **Table 1**, respectively. The blood vessel is composed of three layers: *Tunica Intima*,

*Mechanical Environment in the Human Umbilical Cord and Its Contribution to the Fetal… DOI: http://dx.doi.org/10.5772/intechopen.106565*

#### **Figure 1.**

*Components and spatial arrangement in the computational model of the human umbilical cord. A, the entire image of the model; B and C, the vicinities of the vein and artery, respectively.*

#### **Table 1.**

*Sizes of the human umbilical cord model.*

*Tunica Media*, and *Tunica Adventitia*. The intima is composed of a single layer of endothelial cells, and the adventitia shows a sparse distribution of smooth muscle cells without a clear boundary [19] so that the distinctive two layers of smooth muscle, an inner layer with loosely arranged smooth muscle cells and abundant ground substance, and an outer layer with circularly arranged smooth muscle cells [20], was categorized into *Tunica Media* in this study. The diameter of the umbilical cord, and the inner diameters of the artery and vein were the average values *in vivo* at 40 weeks of gestational age in [8], whose number of cases was larger than other reports [9–14].

**Figure 2.** *Finite element model of the human umbilical cord with triangular mesh (the number of elements, 29, 786).*

"Surroundings" and "Boundary" in the model are corresponding to the surroundings of the umbilical cord and limitations in the displacement of the umbilical cord, whose size was about 1.3 times of the umbilical cord's diameter. The thickness values of the amniotic epithelium, subamniotic zone, and blood vessels have been hardly measured *in vivo* so that each thickness was decided as follows: amniotic epithelium and subamniotic zone, less than 5% of the umbilical cord diameter (0.5 mm); artery and vein, only the layers of smooth muscle cells were modeled, and the thickness in each layer was set as 0.1 mm. The center positions of these blood vessels formed an equilateral triangle, whose sides were equally 8.84 mm. All the blood vessels were equally apart from the umbilical cord at the same distance: at the outer diameter, 0.4 mm. **Figure 2** shows the finite element model of the umbilical cord with triangular meshes (the number of elements, 29, 786). The fixation was set on the region, "boundary."

## **2.2 Mechanical properties**

The arterial and venous pressure *in vivo* has been reported as 88 mmHg and 41 mmHg on average, respectively [7]. While the venous pressure has hardly shown pulsation, the pressure pulsation in the artery, 12 mmHg, has been observed [7]. The size of each component of the model was based on the measurement *in vivo* so that all the shapes would be at the average pressures in the blood vessels. Given that the stress distribution would be homogeneous at the average pressure [30], the change in stress distribution, caused by the pressure rise and drop (12 mmHg (1.6 kPa)), was evaluated. The pressure in the vein was maintained at 0 Pa because of no pulsation.

Reference [28] has shown the mechanical properties of the umbilical vein and Wharton's jelly with two elastic moduli at high and low stress. Because the removal of the amniotic epithelium has not been mentioned, the results of Wharton's jelly would be those of the umbilical cord without the blood vessel. Also, the description of *Tunica adventitia*, which is difficult to separate properly from the surrounding tissue in general, has not been found so that the sample would include *Tunica media* at least. The stress (σ) at a thin-walled cylinder caused by the load of internal pressure (P) is calculated by the following equation:

$$
\sigma = \frac{Pr}{t} \tag{1}
$$

#### *Mechanical Environment in the Human Umbilical Cord and Its Contribution to the Fetal… DOI: http://dx.doi.org/10.5772/intechopen.106565*

where r and t are the radius and thickness of the cylinder, respectively. When the radius, thickness (*Tunica Media* only), and average pressure at the vein were applied to Eq. (1), the stress was more than 0.1 MPa, which was corresponding to the elastic modulus at high stress [28]. Considering that the surrounding tissues would be also at the high stress, the elastic moduli in *Tunica Media* of the vein and amniotic epithelium were set as 2.36 MPa and 11.1 MPa, respectively as **Table 2**, the list of the mechanical property in each component, shows. While the inner layer of the media in the artery was half of that in the media in the vein (1.18 MPa), the other layers around the blood vessels were set as 2.36 MPa. Considering that blood vessel walls would be incompressible in general, Poisson's ratio was set as 0.4999. Because vimentin, desmin, and α- and γ- actin have been found in the subamniotic zone as well as the layers of the blood vessel, the mechanical properties were set as those in the layers. The components of Wharton's jelly, hyaluronan and proteoglycan, contributing to diffusion, would show its compressibility so that Poisson's ratio was set as 0.1. Supposing that the elastic modulus of Wharton's jelly would be between those of the vein and amniotic epithelium, the lower one, corresponding to that of the vein, was set as that of Wharton's jelly. Plenty of fibers observed in amniotic epithelium [23] would hardly show incompressibility so Poisson's ratio was set as 0.3. Given that the umbilical cord could move freely, the elastic modulus of "Surroundings," corresponding to the surroundings of the umbilical cord, was set as 0.1% of that in the layer of the blood vessel. Also, Poisson's ratio of "Surroundings" was set as 0.4.

The active force productions in the layers of the blood vessels, Wharton's jelly, and subamniotic zone, in each model, are shown in **Table 3**. The magnitude of the force generated by the layers of the blood vessels were two types: one was twice of the other. The force direction was set as the opposite to the pressure in the artery. For evaluating the influence of the layers of the blood vessels and others, the force was 0 Pa (negative) at part of the models: Model A, all the force productions were active; Model B, all the force productions were active and the magnitude was twice of those in Model A; Model C, the force productions at the layers of the blood vessels were active; Model D, the force productions at Wharton's jelly and subamniotic zone were active; Model E, no force production.

#### **Table 2.**

*Mechanical properties of the human umbilical cord model.*

#### **Table 3.**

*Active force produced in the components. The plus and negative signs are corresponding to the directions of the pressure, outer and inner directions, respectively.*

#### **2.3 Mechanical environment**

The mechanical environment in the human umbilical cord model was evaluated by von Mises stress (σvm) (equivalent stress), described as below:

$$\sigma\_{\rm VM} = \frac{1}{\sqrt{2}} \left\{ (\sigma\_1 - \sigma\_2)^2 + (\sigma\_2 - \sigma\_3)^2 + (\sigma\_3 - \sigma\_1)^2 \right\}^{1/2} \tag{2}$$

where σ1, σ2, and σ3 are three principal stresses. When σvm is equal to the yield stress of a material, the elastic deformation is changed to plastic one. σvm was used as a parameter that estimates how severe the mechanical environment is.

#### **3. Mechanical environment in the human umbilical cord**

#### **3.1 Pressure rise and drop in the arteries**

**Figure 3** shows the distribution of von Mises stress (σvm) in the umbilical cord model at the pressure rise in the arteries (1.6 kPa). In Models A, and B, where all the components, the layers of the blood vessels, Wharton's jelly, and subamniotic zone, produced active forces, the shapes of the arteries and veins were kept circular. Comparing Model B with Model A, the region for higher σvm around the vein became larger while the region around the arteries reduced. In Models C, D, and E, whose shapes of the blood vessels seemed not circular, higher σvm in the region around the

*Mechanical Environment in the Human Umbilical Cord and Its Contribution to the Fetal… DOI: http://dx.doi.org/10.5772/intechopen.106565*

#### **Figure 3.**

*von Mises stress distribution at the pressure rise in the arteries (1.6 kPa). The black solid line shows the shape before pressure rise. Active force production in each model, indicated in Table 3, is as follows: Model A, in all the components; Model B, in all the components, twice as large as that in A; Model C, in all the layers around the blood vessels; Model D, in Wharton's jelly and subamniotic zone; E, in no component.*

arteries became larger. **Figure 4** shows the distribution of σvm in detail: σvm along the lines in the umbilical cord, depicted in **Figure 3**, is indicated. All the models indicated that the peak of σvm at the artery and vein sides appeared around the amniotic epithelium in all the lines except Line b-b' at the artery side in the models except Model B. Considering that Line b-b' was passing through the region close to the artery and vein, which would be influenced largely by the pressure rise and active force productions, increase in σvm would be reasonable and could be prevented by an increase in the magnitude of the active force. In the meantime, the peak at the artery side of Line b-b' was much smaller than other peaks so that the regions around the blood vessels would keep smaller than those around the amniotic epithelium. The peak of σvm at Models B (vein side), and D and E (artery side) was larger than that in

#### **Figure 4.**

*von Mises stress distribution in detail at pressure rise in the arteries (1.6 kPa). The 6 lines, parallel to each other at the space interval of 0.2 mm from the center to the surroundings (the top of the right side.) were set to examine the stress distribution. The stress along the line in each model is indicated with the circles, corresponding to the peak at the artery and vein sides.*

Models A and C. The magnitude of the active force production at Model B would be too large. And the force produced by the layers of the blood vessels would be necessary to modulate the stress distribution in the umbilical cord.

**Figure 5** shows the distribution of von Mises stress (σvm) in the umbilical cord model at the pressure drop in the arteries (1.6 kPa). Models A and B, where the active forces were produced at all the components, kept the shape of the blood vessels circular. While Model B had the larger region around the vein for higher σvm than

*Mechanical Environment in the Human Umbilical Cord and Its Contribution to the Fetal… DOI: http://dx.doi.org/10.5772/intechopen.106565*

#### **Figure 5.**

*von Mises stress distribution at the pressure drop in the arteries (1.6 kPa). The black solid line shows the shape before pressure drop. Active force production in each model, indicated in Table 3, is as follows: Model A, in all the components; Model B, in all the components, twice as large as that in A; Model C, in all the layers around the blood vessels; Model D, in Wharton's jelly and subamniotic zone; E, in no component.*

Model A, the regions around the arteries for higher σvm in Model B were smaller than those in Model A. The circular shapes of the blood vessels have been hardly kept in Models C, D, and E, with the larger regions around the arteries for higher σvm. These characteristics of the shapes of the blood vessels and distribution pattern of σvm were similar to those in pressure rise as **Figures 3** and **5** show although Models C, D, and E caused the collapses of the arteries and umbilical cord, which were not observed in those models at the pressure rise. **Figure 6** shows the σvm along the lines, which were set as the case of pressure rise in **Figure 4**. The characteristics of all the graphs in **Figure 6** agreed with those in **Figure 4** because the pressures rise and drop had the same magnitude with different directions, and σvm is the function of the difference between the principal stresses as Eq. (2) shows. Hence, through the change in the arterial pressure, the stress around the blood vessels would be kept much lower than that around the amniotic epithelium.

**Figure 6.**

*von Mises stress distribution in detail at pressure drop in the arteries (1.6 kPa). The 6 lines, parallel to each other at the space interval of 0.2 mm from the center to the surroundings (the top of the right side.) were set to examine the stress distribution. The stress along the line in each model is indicated with the circles, corresponding to the peak at the artery and vein sides.*

#### **3.2 Mechanical environment and blood flow in the umbilical cord**

The σvm around the blood vessels (< 6 kPa) was kept much lower than that around the amniotic epithelium (> 12 kPa) when the pressure in the arteries and the active force production was changed. Considering that the adaptations of the blood vessels

*Mechanical Environment in the Human Umbilical Cord and Its Contribution to the Fetal… DOI: http://dx.doi.org/10.5772/intechopen.106565*

and the surrounding tissue to change in the mechanical environment could cause changes in their shapes and structures, the control of the mechanical environment would be effective to keep the shapes and structures of these components in the umbilical cord. Also, considering the adaptation and damage in the amniotic epithelium might be necessary. In the meantime, the shape of the blood vessels would be hardly kept unless the active forces were produced by all the components. The shape of the blood vessel would directly influence the blood flow pattern and cause change in wall shear stress, which could damage the blood vessel function and structure. Also, the collapse of the umbilical cord at the pressure drop with the active forces, which were produced partially, could damage its tissue structure. Hence, the active force productions at all the components would be necessary to maintain the proper blood flow in the umbilical blood vessels and avoid the damage to the tissue of the umbilical cord.

#### **4. Conclusion**

The human umbilical cord model for finite element analysis, based on the mechanical and histological characteristics, has been developed. The influence of the active force productions by hyaluronan, proteoglycan, smooth muscle cells, and myofibroblasts on the stress distribution in the umbilical cord was evaluated. As a result, the active forces produced by all the components would be necessary to maintain the blood flow properly.

#### **Acknowledgements**

This work was supported by Grant for Individual Research of Tohoku-Gakuin in 2021.

#### **Conflict of interest**

The author declares no conflict of interest.

#### **Author details**

Yoko Kato Faculty of Engineering, Tohoku Gakuin University, Miyagi, Japan

\*Address all correspondence to<EMAIL_ADDRESS>
© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.