**3. Results and Discussion**

#### *3.1. Farmers' Characteristics and Remediation Intention*

With the development of existing soil remediation projects and a better understanding of the two remediation technologies, farmers' intentions for soil remediation have changed, and phytoremediation has become a popular remediation mode. Farmers with farmland transferred for soil remediation were defined as those participating in remediation. Among the 553 sample farmers, 22.6% did not participate in remediation, 54.1% participated in phytoremediation, 13.9% participated in passivation, and 9.4% participated in both remediation modes. Regarding future soil remediation intentions, 4.7% of the sample farmers believed that the soil did not need remediation, 82.8% expressed a preference for phytoremediation, and 12.5% preferred passivation (Figure 4a).

**Figure 4.** Farmers' characteristics and remediation intention. Future intentions of farmers with different (**a**) current participation, (**b**) gender, (**c**) agricultural labor, (**d**) farmland, (**e**) farm income, (**f**) project income for soil remediation.

Among the objective indicators of the sample farmers' characteristics (Supplementary Table S2), there were significant differences (*p* < 0.05) in soil remediation intentions among different levels of the population in terms of gender, agricultural labor, farmland, farm income, and project income.

• Women had a greater willingness to remediate than men (Figure 4b). Studies often show that women in agriculture are more environmentally conscious than men [38], which may be related to the fact that women are generally more risk-averse than men [25,39,40];

Agricultural research has observed relationships between farmers' environmental behavior and various demographic characteristics, such as age, education, and gender, which may be associated with decisions to participate in agri-environmental programs [38]. Many studies have shown that farmer's age and education level are key factors influencing their environmental behaviors [27]. Younger farmers are more likely to engage in adaptive production behaviors or environmental improvements than older farmers [27,44], and farmers with higher education levels are more likely to engage in health-related adaptive behaviors [19]. In contrast, farmers' willingness to remediate soil in this study was not significantly related to their age or education level. This may be explained by the high attrition of young labor in our study area (only 3.1% under the age of 40) and the generally low educational attainment of the remaining middle-aged and older labor force (only 8.5% high school and above), a common phenomenon in rural China, resulting in an under-representation of younger and better-educated farmers in the samples.


**5. Summary and conclusions**

190 Petri Nets – Manufacturing and Computer Science

**Table 3.** Resources usage

**Figure 16.** Simulation results in *Active-HDL*

17], this aspect is however not discussed further in this chapter.

Input signals value changes come from outside and are not modified inside VHDL model

VHDL file can also be simulated i.e. in *Active-HDL* environment [4]. Simulation confirms the proper functionality of designed logic controller (simulation results are presented in Figure 16). It is then possible to perform logic synthesis and implementation, i.e. in *Xilinx PlanAhead* environment, in version *13.1* [21]. Sample resources usage for the *xa6slx4csg225-2* circuit

**Resource Utilization Available Utilization Register** 18 4800 1% **LUT** 18 2400 1% **Slice** 6 600 1% **IO** 27 132 20% **Global Clock Buffer** 1 16 6%

It is also possible to transform logical model into synthesizable code in Verilog language [9,

file. Their values are just read out by conditions related to transition firings.

from *Spartan6* family of *XILINX* [22] is listed in Table 3.

Proposed novel approach to verification of reconfigurable logic controller programs and specification by means of Control Interpreted Petri Nets allows to detect even subtle errors on an early stage of system development. Rule-based representation of Control Interpreted Petri Nets in temporal logic is presented at RTL-level and is easy to formally verify using model checking technique and to synthesize using hardware description languages.

Results of the work include the assurance that verified behavioural specification in temporal logic will be an abstract program of matrix reconfigurable logic controller. Hence, logic controller program (its implementation) will be valid according to its primary specification. This may shorten the duration time of logic controllers development process (as early discovered errors are faster corrected) and, consequently, save money (as project budgets will not be exceeded).

Furthermore, formal verification can improve the quality of final products, making them work more reliable. And even if a logic controller, already delivered to customer, will not work properly (it can always happen that some subtle error was overseen or that the specification was incomplete), it is possible to find error source using available techniques (verification, simulation, etc.). Then, some part of corrected system (or the whole system) may be one more time formally verified using extended requirements list and modified logical model.

Future research directions include i.e. (but are not limited to) model checking of other forms of logic controllers specification and mechanisms for behavioural properties specification.


A Study on Contractors' Perception of Using Wood for Construction

*Hüseyin Emre Ilgın, Markku Karjalainen, Olli-Paavo Koponen and Anu Soikkeli*

## **Abstract**

Construction work is very resource-intensive, and construction projects contain many parameters, in which the choice of building material is one of the critical decisions with numerous criteria, e.g., cost, durability, and environmental impact. Moreover, this complex process includes different parties such as contractors, architects, engineers, where contractors are the most influential decision-makers in material selection. Increasing the use of renewable materials such as wood, which is a technically, economically, and environmentally viable alternative in buildings, can make construction more sustainable. The perceptions of the contractors influence what they propose and therefore the increase in wood construction. With the increasing resource efficiency and the need to adapt to climate change in the construction industry, there is need for contractors to implement sustainable practices. In this chapter, contractors' perceptions of the use of wood in buildings were examined. The results are expected to contribute to environmental remediation by developing strategies to counter perceived barriers and providing insight into new solutions to a conservative space and expanding the use of wood to achieve a more sustainable construction industry. In addition, recommendations for future research, e.g., adhesive- and metal-fastener-free dovetail wood board elements as sustainable material alternatives were presented.

**Keywords:** engineered wood products, construction, contractors, perception, carbon footprint

## **1. Introduction**

The last two decades have witnessed a dramatic increase in environmental awareness and concern about the impacts of business activities on climate and natural resources on a global scale, and environmental degradation is often addressed as a worldwide problem [1–6]. In this sense, the building construction industry can contribute significantly to the reduction of CO2 emissions, high energy consumption, excessive waste, and the development of a more resource-efficient and sustainable building environment [7–10]. More specifically, construction activities involve the use of a wide variety of materials, such as concrete, steel, timber where the choice of these materials has significant impacts on the environment [11, 12] as in the cases of tall timber buildings such as the 25-story and 87 m high Ascent

(Milwaukee, structurally topped out) (**Figure 1**), the 22-story and 73 m high HAUT (Amsterdam, under construction) (**Figure 2**), and the 18-story and 58 m high Brock Commons Tallwood House (Vancouver, 2017) (**Figure 3**) [13].

There are several criteria to consider in the selection of building materials, including stability, durability, environmental impact, speed of assembly, cost, and availability [14, 15]. Although design professionals are often involved in this process [16], contractors have the most influence in material selection decisions and therefore play an important role in supporting sustainable development in the context of the construction industry [8, 17, 18].

With the increasing resource efficiency and the need to adapt to climate change in the construction industry, contractors need to execute sustainable practices. However, contractors' decision-making and perceptions of structural frameworks remain largely unexplored, and there are few studies on the selection of structural frameworks involving contractors' perspectives (e.g., [7, 8, 19]).

Wood is the primary building material used by mankind throughout history, a sustainable and renewable building material [20, 21]. The use of wood in construction can affect carbon balance by reducing fossil fuel consumption in manufacturing compared with alternative materials, preventing emissions from cement processing, and storing carbon in wood products and forests. Thus, increasing the use of wood in construction and other long-lasting uses will help achieve sustainable development goals, where timber is recognized as a sustainable material in all major green building rating tools, e.g., Leadership in Energy and Environmental Design (USA) and the BRE Environmental Assessment Method (UK).

Wooden buildings are characterized by a lower carbon construction concept than non-wood buildings [22–26], and timber construction represents a lower embodied energy consumption compared with steel and concrete production [7]. Wooden structures provide significant advantages in combating climate change, because wood can be used as an alternative to other materials to reduce greenhouse gas emissions, but also has unique features such as storing large amounts of carbon in the structure [27, 28]. For example, estimated environmental impact of wood use in Brock Commons Tallwood House (**Figure 3**) was calculated as 1753 metric tons of CO2 in terms of carbon stored in the wood [29]. Besides being used as a building material during the construction, wood can be reused as a raw material for other structures after the building's service life or, as a last resort, burned

**Figure 1.** *Ascent (Image courtsey of Jason Korb/Korb + Associates Architects).*

*A Study on Contractors' Perception of Using Wood for Construction DOI: http://dx.doi.org/10.5772/intechopen.103168*

**Figure 2.** *HAUT (Photo courtsey of Jannes Linders).*

**Figure 3.** *Brock Commons Tallwood House (Photo by Michael Elkan and courtsey of Acton Ostry Architects).*

instead of fossil fuels [30–32]. The use of wood has many other advantages such as esthetic value, better design adaptability, ease of construction, living comfort, and indoor quality [15, 33, 34].

A better understanding of the perspectives of key actors, such as contractors, in the selection of structural frameworks, can improve insights into concrete path dependency. Because of the CO2 effects of structural frameworks, such knowledge contributes to understanding the key factors for the development of a more sustainable built environment.

Overall, this chapter examines the perceptions of the contractors regarding the use of wood in buildings. It is believed that the results will contribute to environmental remediation by developing strategies against perceived barriers and providing insight into new solutions to a conservative space and expanding the use of wood to achieve a more sustainable construction industry.

In this chapter, wood or timber refers to engineered wood products (EWPs) [35, 36] such as CLT (a prefabricated multilayer EWP, manufactured from at least three layers of boards by gluing their surfaces together with an adhesive under pressure), laminated veneer lumber (LVL; made by bonding together thin vertical softwood veneers with their grains parallel to the longitudinal axis of the section, under heat and pressure), and glue-laminated timber (glulam) (abbreviated as GL; made by gluing together several graded timber laminations with their grains parallel to the longitudinal axis of the section).

## **2. Studies on contractors' perceptions of the use of wood for construction**

In the literature, many studies focus on the technological aspects of EWPs, their use in construction, and different building solutions [37–50]. Several studies address wood as a structural material in buildings from the perspectives of key professionals (e.g., [8, 17, 51–58]) and consumers or residents (e.g., [59–64]); while there is a very limited number of works focusing on EWPs from the contractors' perspective in the literature. They are from different countries such as Sweden, Finland, Australia focusing on the use of wood as a structural material through surveys and/or interviews.

Among the studies, Hemström et al. [8] conducted interview-based research among contract managers working in contracting companies about their role in the sociotechnical regime, the choice of structural framework, and their perceptions of different alternatives. The results showed that because of their critical position in the firm, managers greatly influence the choice of the structural framework for multifamily buildings managed by the established concrete-based sociotechnical regime. The results also indicated that, due to cognitive rule-based decision-making processes, when assessing the cost of different structural frameworks, they applied their previous experience with concrete solutions as a structural material rather than making deep cost assessments. This approach has prevented timber-framed multifamily buildings from entering common use. While strong incentives for the use of concrete have made it difficult for timber frames to become more common, initiatives promoting wood could contribute to increased awareness and perceptions of wood construction and expectations for future developments in Sweden.

Riala and lola [19] conducted a study through 18 interviews with representatives from the entire value chain to identify the barriers to the adoption of multistory timber construction in Finland, the ways that wood competes with established solutions, and the possibilities for partially integrating construction into the bioeconomy. The results showed that although barriers to its adoption still exist,

multistory timber construction can offer competitive solutions for more sustainable construction. A noteworthy finding of concern for the wood products industry was that interviewees with the most experience in multistory timber construction were more critical than those with less experience. This showed that building more wood and gaining more experience is not enough to increase the popularity of wood construction. Additionally, limited possibilities were found to relate the construction industry to bioeconomy. The best way to ensure greater use of renewable materials in multistory construction would be to focus on increasing the competitiveness of multistory timber construction. For this, it was necessary to take advantage of the strengths of the wooden structure such as lightness and prefabrication possibilities and focus on improvement.

Through the qualitative analysis of the data from 36 interviews, Wang et al. [7] examined the perceptions and insights of British construction experts (e.g., industry interest group, timber manufacturer, construction material merchant) to increase understanding of Green Building and the potential of using wood for the UK construction industry. The results confirmed the important role played by the British government in the creation, promotion, and development of Green Building and showed a positive increase in the use of wood in the UK construction industry, supporting the idea that the environmental performance of wood was the main factor in wood adoption. Experts with sound knowledge of wood as a building material were also shown to agree on wood's superior environmental properties; however, end-users who do not know about wood products often have a strong prejudice against their use. Finally, it was shown that legislation, environmental awareness, attitudes and traditions, market and competition, publicity and communication, and technology and know-how are among the main drivers promoting wood as a sustainable solution for Green Building in the UK construction industry. Additionally, most respondents rated the lack of education as one of the most prominent challenges in the current construction industry, hindering the expansion of potential applications of wood products. Following the discussion on wood providing the optimal solution for Green Building (e.g., [21, 65]), the study found a generally positive attitude toward the use of wood in the UK construction industry and found support for the idea that environmental performance is the main driver for wood adoption in the Green Building concept.

Through a survey of 74 experienced construction industry participants (e.g., architects, contractors, developers, and government officials), Xia et al. [11] explored the main barriers to the use of timber framing in multistory construction in Australia. According to the results, the barriers identified can be broadly divided into five groups: lack of legal support, lack of industry interest, lack of experienced professionals, perception of wood framing disadvantages, and limited awareness of wood framing advantages. The survey confirmed the limited awareness of the new wood technologies available, as well as the biggest barriers to the perceived increase in maintenance costs and fire risk. The results are expected to benefit the government and the timber industry by contributing to environmental remediation by developing strategies to increase the use of multistory timber technologies by countering perceived barriers in the Australian context. One approach to overcoming these barriers might be the collaboration of various stakeholders such as governments, customers, designers, and contractors. It was suggested that the government may introduce more supportive legislation and regulations to encourage the use of wood for structural purposes. Industry training (e.g., workshops and seminars) and education in timber structures might have contributed to increasing awareness and knowledge of technological innovations in wood products in the construction industry.

Tan et al. [66] extensively reviewed studies on the relationship between sustainability performance and contractors' competitiveness. The results indicated that there was no unique relationship between the two variables. Therefore, a framework for the implementation of sustainable construction practices was developed to increase competitiveness to help contractors develop their sustainability policies, strategies, and practices to meet the growing need for sustainable development in the construction industry.

Qi et al. [4] aimed to identify the factors affecting contractors' adoption of green construction practices through a survey. The results showed that managerial concern is the most important driver in the adoption of green practices. Significant relationships were also found between government regulation and enterprise size, along with the adoption of green construction practices, while there was no substantial evidence of the relationship between the adoption of green construction practices and perceived stakeholder pressures. This study aimed to contribute to better decision-making regarding the implementation of green construction practices.

## **3. Conclusions and recommendations**

This study aimed to understand the contractors' perceptions of the use of wood for construction. In doing so, this chapter attempted to identify perceived major barriers to timber utilization. However, as the focus of conducted research among contractors differed as noted above, it was not possible to compare these studies with each other, but still, some conclusions were reached as follows: (a) their previous experience with concrete solutions, especially as a structural material, could have prevented them from conducting in-depth analysis for new materials; (b) building more wood and gaining more experience may not be enough to increase the popularity of wood construction; (c) lack of legal support, lack of industry interest, lack of experienced professionals, lack of education, perception of wood framing disadvantages, and limited awareness of wood framing advantages as well as the perceived

**Figure 4.** *Adhesive- and metal fastener-free dovetail wood board element.*

#### *A Study on Contractors' Perception of Using Wood for Construction DOI: http://dx.doi.org/10.5772/intechopen.103168*

increase in maintenance costs and fire risk were cited as barriers to wood use; (d) managerial concern was among the most important drivers for the adoption of green practices related to wood use.

In this context, the following recommendations can help address identified issues among contractors by improving general attitudes toward the use of wood: (1) providing initiatives that promote wood for increasing awareness and perception of wood construction and prospects for future developments; (2) increasing competitiveness by highlighting the strengths of wooden structure such as lightness and prefabrication possibilities; (3) establishing collaboration of critical stakeholders such as governments, customers, designers, and contractors;

(4) introducing more supportive legislation and regulations at the government level to encourage the use of wood for structural purposes; (5) organizing industry training (e.g., workshops and seminars) and education in wooden structures to increase awareness and knowledge of technological innovations in wood products in the construction industry; (6) conducting more research projects (e.g., the DoMWoB project/Dovetailed Massive Wood Board Elements for Multi-Story Buildings – *see Acknowledgments and Funding*) [67] and developing more innovative and environmentalist EWPs (e.g. adhesive- and metal-fastener-free dovetail wood board elements) (**Figure 4**) [68] to demonstrate the potential of wood for use in construction.

It is believed that this chapter will help deepen the understanding of the various aspects that shape the decision-making process particularly among contractors in the use of EWPs for construction.

## **Acknowledgements**

This project has received funding from the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No [101024593].

## **Funding**

This project has also received funding (60 000 EUR) from the Marjatta and Eino.

Kolli Foundation for funding the technical performance tests including fire safety, structural, moisture transfer resistance and air-tightness, and sound insulation.

*Engineered Wood Products for Construction*

## **Author details**

Hüseyin Emre Ilgın1 \*, Markku Karjalainen1 , Olli-Paavo Koponen1 and Anu Soikkeli2

1 Tampere University, Tampere, Finland

2 University of Oulu, Oulu, Finland

\*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.

*A Study on Contractors' Perception of Using Wood for Construction DOI: http://dx.doi.org/10.5772/intechopen.103168*

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[59] Karjalainen M, Ilgın HE, Somelar D. Wooden Extra Stories in Concrete Block of Flats in Finland as an Ecologically Sensitive Engineering Solution, Ecological Engineering—Addressing

*A Study on Contractors' Perception of Using Wood for Construction DOI: http://dx.doi.org/10.5772/intechopen.103168*

Climate Challenges and Risks. IntechOpen: London, UK; 2021

[60] Karjalainen M. The Finnish Multi-Story Timber Apartment Building as a Pioneer in the Development of Timber Construction. Oulu, Finland: University of Oulu; 2002 (In Finnish)

[61] Karjalainen M, Ilgın HE. The change over time in Finnish Residents' attitudes towards multi-story timber apartment buildings. Sustainability. 2021;**13**:5501

[62] Lähtinen K, Harju C, Toppinen A. Consumers' perceptions on the properties of wood affecting their willingness to live in and prejudices against houses made of timber. Wood Material Science and Engineering. 2019;**14**:325-331

[63] Kylkilahti E, Berghäll S, Autio M, Nurminen J, Toivonen R, Lähtinen K, et al. A consumer-driven bioeconomy in housing? Combining consumption style with students' perceptions of the use of wood in multi-story buildings. Ambio. 2020;**49**:1943-1957

[64] Karjalainen M, Ilgın HE, Metsäranta L, Norvasuo M. Residents' attitudes towards wooden facade renovation and additional floor construction in Finland. The International Journal of Environmental Research and Public Health. 2021;**18**:12316

[65] Gustavsson L, Joelsson A, Sathre R. Life cycle primary energy use and carbon emission of an eight-storey wood-framed apartment building. Energy and Buildings. 2010;**42**(2): 230-242

[66] Tan YT, Shen LY, Yao H. Sustainable construction practice and contractors' competitiveness: A preliminary study. Habitat International. 2011;**35**:225-230

[67] Ilgın HE, Karjalainen M. Preliminary design proposals for dovetail wood board elements in multi-story building construction. Architecture. 2021;**1**:56-68

[68] Ilgın HE, Karjalainen M, Koponen O. Various Geometric Configuration Proposals for Dovetail Wooden Horizontal Structural Members in Multistory Building Construction. IntechOpen: London, UK; 2022

## **Chapter 7**


*TPRN (DFNB79)*

258 Hearing Loss

*GIPC3* encodes a PDZ domain containing protein which is important in peripheral auditory signal transmission. Mutations in this gene cause both profound deafness and progressive hearing loss. In a small Dutch hearing loss followed a different course in the two affected siblings. In the oldest affected individual, the loss in hearing was 70 dB HL at 11 months which progressed to 110 dB HL by 12 years of age. The hearing loss in second individual was 80 dB HL at 3 months which seemed to be stable as it only progressed to 90 dB HL by age of 14 years. (Charizopoulou et al., 2011). The mutation in *GIPC3* identified in the Dutch family introduces a stop codon in exon 6 (p.W301X) truncating the C-terminal. It is hypothesized that since this mutation is in the last exon it will not cause nonsense mediated

*GIPC3* mutations have also been reported in seven other large families from Pakistan which include one framsehift and and six missense mutations (Rehman et al., 2011). The younger affected individuals in these families (7 and 9 years old) had better hearing as compared to the older affected individuals (20 and 25 years old). However, information is not available as

A mutation affecting PDZ domain of GIPC3 has also been reported in mice which causes progressive hearing loss, *ahl5* (Charizopoulou et al., 2011). The mice have a moderate hearing loss at one month of age which progresses to profound in degree by 1 year of age. The higher frequencies are affected first with eventual involvement of all frequencies. DPOAE and the endocochlear potential are gradually affected as well. The stereocilia are

*BSND* encodes barttin which is an essential subunit for two chloride channels. Heteromeric channels formed by barttin and the chloride channels play an important role in potassium recycling in the inner ear (Estevez et al., 2001)*.* A missense mutation, p.I12Tof BSND segregates with hearing loss in three families from Pakistan while in a fourth family it is present with a nonsense mutation in compound heterozygosity (Riazuddin et al., 2009). The younger individuals have a less severe hearing loss as compared to the older affected individuals suggesting that *BSND* may be involved in aetiology of progressive deafness. Functional analysis of the p.I12T mutation of *BSND* in HEK293T cells have demonstrated that function of the channels is unaffected. However, the number of channels on the surface membrane is reduced which results in a decreased current amplitude (Riazuddin et al., 2009).

The 15 PLAT (polycystin/lipoxygenase/a-toxin) domains encoding gene *LOXHD1* was found to be mutated in an Iranian family with postlingual onset of hearing loss at ages ranging from 7 to 8 years. Affected individuals in the family had preserved hearing at low frequencies in the beginning. The loss was mild to moderate at frequencies of 0.5 to 2 KHz. Hearing loss worsened during childhood and adolescence to moderate to severe at mid and high frequencies. All frequencies were affected eventually (Grillet et al., 2009). A nonsense mutation, p.R670X was identified which introduces a premature stop codon at the Cterminal end of f the fifth PLAT domain. This could either lead to a protein lacking 10 PLAT

decay and will allow production of a mutant protein retaining some function.

yet whether hearing loss in any of the affected individuals is stable or progressive.

defective and degenerate together with the spiral ganglion cells.

*GIPC3 (DFNB72/15/95)*

*BSND (DFNB73)*

*LOXHD1 (DFNB77)*

Mutations of *TPRN* cause different degrees of hearing loss in humans. In a Dutch family, hearing loss is documented as moderate to severe in degree till 11 years of age and by 15 years it progresses to profound deafness (Li et al., 2010). In contrast, hearing loss in a Moroccan family is severe in degree even in the third decade of life (Li et al., 2010). Affected members of the Dutch family had a nonsense mutation in exon 1 of *TPRN* while the affected individuals in the Moroccan family were homozygous for a frameshift mutation in exon 1. It is interesting to note that the same frameshift mutation as observed in the Moroccan family was also identified in a Pakistani family. However, individuals in this family had profound degree of deafness (Khan et al., 2009; Rehman et al., 2010).

TPRN is present in the supporting cells as well as at the base of hair cells' stereocilia in the organ of Corti at the taper region of each stereocilium just above the cuticular plate (Rehman et al., 2010).

### *PTPRQ (DFNB84)*

Congenital hearing loss which has been shown to be progressive in nature is associated with mutations in *PTPRQ*, a gene which encodes a phosphatase specific for phoshatidyl inositol, PI(4,5)P2 (Schraders et al., 2010b; Seifert et al., 2003). PI(4,5)P2 plays an important part in actin remodeling. Hearing loss due to mutations *PTPRQ* is severest in a Dutch family with a p.Y497X mutation and hearing loss was self reported to have progressed to profound by the third to fourth decade of life. However in affected individuals of a Moroccan family, a p.R457G mutation in PTPRQ caused a less severe loss in hearing. The loss in hearing was moderate which had deteriorated with age (Schraders et al., 2010b). Otoacoustic emissions were normal at the age of 13 months. The 1 to 2 KHz frequencies seemed to be more affected comparable to that observed in members of a Palestinian family with moderate to severe hearing loss also with a mutation of *PTPRQ* (Shahin et al., 2010a). In the Palestinian family, there were four affected individuals with considerable variation of hearing loss. A nonsense mutation, p.Q429X, was observed in *PTPRQ* for this family (Shahin et al., 2010a). Data is not available about progression of deafness in the Palestinian family*.*

*Ptprq* is transiently expressed over a period of first three weeks in mouse hair cells at the basal turn of the cochlea (Goodyear et al., 2003). MYO6 plays a role in localization of PTPRQ

Genetics of Nonsyndromic Recessively Inherited

where widespread loss of outer hair cells is observed.

complex.

*USH2A (USH2A)*

*GPR98 (USH2C)*

(McGee et al., 2006). *WHRN (USH2D)*

Moderate to Severe and Progressive Deafness in Humans 261

Hearing loss for USH2 can vary from mild to severe in degree and may also show interfamilial variation (Abadie et al., 2011). The four Usher genes are expressed in hair cells where except for CLRN1, all proteins interact at the ankle link in the stereocilia and form a

Usher type 2A is the most frequent cause of Usher syndrome. A large number of missense, nonsense, insertion and deletion mutations have been identified in *USH2A*. The mutations were first described in North European, Spanish and African American patients (Eudy et al., 1998). *USH2A* encodes a large transmembrane protein, usherin, with an intracellular PDZ binding domain. Usherin is present in both outer and inner hair cells stereocilia and cannot be detected by 2 months of age in mice (Liu et al., 2007). *Ush2a-/-* transgenic mice have a moderate, non-progressive hearing loss which is more noticeable at high frequencies, mimicking the phenotype observed in humans (Liu et al., 2007). In the ears of the *Ush2a-/* mice the inner hair cells and stereocilia are intact in all but at the basal turn of the cochlea

Mutations of *GPR98* or *VLGR1* were first described in USH2 patients from United States and Sweden (Weston et al., 2004). *Gpr98* is expressed transiently during the first week in mice and is no longer detectable by P11*.* GPR98 forms the ankle links that connect the stereocilia of hair cells at their base in the developing hair cell bundles*.* Transgenic *Vlgr1/del7TM* mice which lack transmembrane and cytoplasmic domains of the protein are severely deaf by third week of life and lack ankle links (McGee et al., 2006). The stereocilia are arranged in a more rounded shape as compared to the "V" like pattern present in the wild type mice. A gradual loss of both type of hair cells and pillar cells is observed at the base of the cochlea

The description of *USH2D (WHRN)* is based on only two families from Germany and Portugal. The patients in the German family had mild to moderate hearing loss (Ebermann et al., 2007a) while the Portuguese family had variable degree of hearing loss with post lingual onset which was progressive in nature (Audo et al., 2011). In the German family two mutations in *WHRN* were detected in compound heterozygosity, involving a nonsense mutation in exon 1 and a splice site mutation in intron 2. The splice site mutation causes an in-frame skipping of the second exon and is predicted to result in production of an aberrant protein (Ebermann et al., 2007a). In the Portuguese family a deletion mutation was detected in exon 2 which is predicted to truncate the protein or mark the message for nonsense mediated decay (Audo et al., 2011). These mutations disrupt only the long isoform of WHRN. Mice with a targeted deletion of the long isoform of whirlin have some partial hearing (75 dB SPL) which is non-progressive in nature (Yang et al., 2010) . The inner hair cells stereocilia are unaffected while the outer hair cells stereocilia loose their characteristic "V" shaped formation and assume a "U" shape. Some of the stereocilia are missing from the innermost row in outer hair cells. However, unlike *whirler* mutant mice who are deaf due to a deletion in *Whrn* disrupting both isoforms of the protein, mice with targeted ablation of

the long isoform of whirlin do not have abnormally short stereocilia.

in plasma membranes (Sakaguchi et al., 2008). PTPRQ has been shown to be required for formation of shaft connectors and the taper of the stereocilia (Goodyear et al., 2003; Sakaguchi et al., 2008). Two transgenic mouse mutants, *Ptprq-TM-KO* and *Ptprq-CAT-KO* were generated in which the alleles encode proteins lacking transmembrane and catalytic domains of PTPRQ respectively (Goodyear et al., 2003). Cochlear development was normal in both mice and there was progressive deterioration of the sensory epithelium. Inner hair cells abnormalities were apparent by P1. Some stereocilia were misaligned or missing in the basal turn of cochlea. Stereocilia eventually fused and ultimately the organ of Corti disappeared in some mice by the age of three months (Goodyear et al., 2003).

#### *SERPINB6 (DFNB91)*

A single Turkish family has been described in which affected individuals have a mutation in *SERPINB6* segregating with hearing loss. The nonsense mutation, p.E245X was shown to substantially decrease the amount of the mutant transcript in blood of affected individuals (Sirmaci et al., 2010). The degree of hearing loss is moderate to severe with some residual hearing in all affected individuals. The 54 year old individual was the oldest and had the severest degree of hearing loss with greater degree of loss at high frequencies. The two younger individuals 24 and 23 years respectively, presented with moderate to severe hearing loss which was more severe in the 23 year old patient. Progressive nature of hearing loss was self reported by affected individuals but had not been documented by audiometry.

SERPINB6 is present in the hair cells in the organ of Corti as well as the greater epithelial ridge and may function as an inhibitor of proteases. It is hypothesized that SERPINB6 prevents non-specific tissue damage to inner ear tissue by inhibiting proteases. A transgenic mouse line lacking *Serpinb6* was created (Scarff et al., 2004) but the hearing status of the mice and inner ear structure was not evaluated. It will be interesting to identify if *Serpinb6-/-* mice have deafness at onset of hearing or whether they exhibit progressive deafness.

So far the results of genetic studies have revealed that although moderate to severe hearing loss is the usual finding for individuals with mutations in *STRC*, *TECTA* and *OTO* and in some individuals with mutations which cause progressive deafness, some individuals with mutations in other genes, for example *GJB2*, *CLDN14* or *TRIC* also have similarly milder phenotypes. Additionally, identical mutations in a gene may cause either progressive or stable hearing loss (Bashir et al. manuscript in preparation). Research has also shown that genes involved in progressive hearing loss may also have implications for age related hearing loss. For example, a polymorphism in *Cdh23* has been associated with age related hearing loss in different mice strains (Noben-Trauth, Zheng & Johnson, 2003).

#### **2.4a Moderate to severe or progressive deafness in Usher Syndrome**

Usher syndrome (USH) is a common syndrome of deafness-blindness and can be easily misdiagnosed as nonsyndromic hearing loss since onset of retinitis pigmentosa is gradual and the early manifestation can be very mild in some cases. So far mutations in 4 genes have been identified which cause the less severe phenotypes of hearing loss in Usher syndrome (*USH2A*, *GPR98*, *WHRN* and *CLRN1*). Additionally, some mutations of genes which cause Usher type 1 can also cause phenotypes termed as atypical usher syndromes.

Hearing loss for USH2 can vary from mild to severe in degree and may also show interfamilial variation (Abadie et al., 2011). The four Usher genes are expressed in hair cells where except for CLRN1, all proteins interact at the ankle link in the stereocilia and form a complex.

#### *USH2A (USH2A)*

260 Hearing Loss

in plasma membranes (Sakaguchi et al., 2008). PTPRQ has been shown to be required for formation of shaft connectors and the taper of the stereocilia (Goodyear et al., 2003; Sakaguchi et al., 2008). Two transgenic mouse mutants, *Ptprq-TM-KO* and *Ptprq-CAT-KO* were generated in which the alleles encode proteins lacking transmembrane and catalytic domains of PTPRQ respectively (Goodyear et al., 2003). Cochlear development was normal in both mice and there was progressive deterioration of the sensory epithelium. Inner hair cells abnormalities were apparent by P1. Some stereocilia were misaligned or missing in the basal turn of cochlea. Stereocilia eventually fused and ultimately the organ of Corti

A single Turkish family has been described in which affected individuals have a mutation in *SERPINB6* segregating with hearing loss. The nonsense mutation, p.E245X was shown to substantially decrease the amount of the mutant transcript in blood of affected individuals (Sirmaci et al., 2010). The degree of hearing loss is moderate to severe with some residual hearing in all affected individuals. The 54 year old individual was the oldest and had the severest degree of hearing loss with greater degree of loss at high frequencies. The two younger individuals 24 and 23 years respectively, presented with moderate to severe hearing loss which was more severe in the 23 year old patient. Progressive nature of hearing loss was self reported by affected individuals but had not been documented by

SERPINB6 is present in the hair cells in the organ of Corti as well as the greater epithelial ridge and may function as an inhibitor of proteases. It is hypothesized that SERPINB6 prevents non-specific tissue damage to inner ear tissue by inhibiting proteases. A transgenic mouse line lacking *Serpinb6* was created (Scarff et al., 2004) but the hearing status of the mice and inner ear structure was not evaluated. It will be interesting to identify if *Serpinb6-/-* mice

So far the results of genetic studies have revealed that although moderate to severe hearing loss is the usual finding for individuals with mutations in *STRC*, *TECTA* and *OTO* and in some individuals with mutations which cause progressive deafness, some individuals with mutations in other genes, for example *GJB2*, *CLDN14* or *TRIC* also have similarly milder phenotypes. Additionally, identical mutations in a gene may cause either progressive or stable hearing loss (Bashir et al. manuscript in preparation). Research has also shown that genes involved in progressive hearing loss may also have implications for age related hearing loss. For example, a polymorphism in *Cdh23* has been associated with age related

Usher syndrome (USH) is a common syndrome of deafness-blindness and can be easily misdiagnosed as nonsyndromic hearing loss since onset of retinitis pigmentosa is gradual and the early manifestation can be very mild in some cases. So far mutations in 4 genes have been identified which cause the less severe phenotypes of hearing loss in Usher syndrome (*USH2A*, *GPR98*, *WHRN* and *CLRN1*). Additionally, some mutations of genes which cause

have deafness at onset of hearing or whether they exhibit progressive deafness.

hearing loss in different mice strains (Noben-Trauth, Zheng & Johnson, 2003).

**2.4a Moderate to severe or progressive deafness in Usher Syndrome**

Usher type 1 can also cause phenotypes termed as atypical usher syndromes.

disappeared in some mice by the age of three months (Goodyear et al., 2003).

*SERPINB6 (DFNB91)*

audiometry.

Usher type 2A is the most frequent cause of Usher syndrome. A large number of missense, nonsense, insertion and deletion mutations have been identified in *USH2A*. The mutations were first described in North European, Spanish and African American patients (Eudy et al., 1998). *USH2A* encodes a large transmembrane protein, usherin, with an intracellular PDZ binding domain. Usherin is present in both outer and inner hair cells stereocilia and cannot be detected by 2 months of age in mice (Liu et al., 2007). *Ush2a-/-* transgenic mice have a moderate, non-progressive hearing loss which is more noticeable at high frequencies, mimicking the phenotype observed in humans (Liu et al., 2007). In the ears of the *Ush2a-/* mice the inner hair cells and stereocilia are intact in all but at the basal turn of the cochlea where widespread loss of outer hair cells is observed.

#### *GPR98 (USH2C)*

Mutations of *GPR98* or *VLGR1* were first described in USH2 patients from United States and Sweden (Weston et al., 2004). *Gpr98* is expressed transiently during the first week in mice and is no longer detectable by P11*.* GPR98 forms the ankle links that connect the stereocilia of hair cells at their base in the developing hair cell bundles*.* Transgenic *Vlgr1/del7TM* mice which lack transmembrane and cytoplasmic domains of the protein are severely deaf by third week of life and lack ankle links (McGee et al., 2006). The stereocilia are arranged in a more rounded shape as compared to the "V" like pattern present in the wild type mice. A gradual loss of both type of hair cells and pillar cells is observed at the base of the cochlea (McGee et al., 2006).

#### *WHRN (USH2D)*

The description of *USH2D (WHRN)* is based on only two families from Germany and Portugal. The patients in the German family had mild to moderate hearing loss (Ebermann et al., 2007a) while the Portuguese family had variable degree of hearing loss with post lingual onset which was progressive in nature (Audo et al., 2011). In the German family two mutations in *WHRN* were detected in compound heterozygosity, involving a nonsense mutation in exon 1 and a splice site mutation in intron 2. The splice site mutation causes an in-frame skipping of the second exon and is predicted to result in production of an aberrant protein (Ebermann et al., 2007a). In the Portuguese family a deletion mutation was detected in exon 2 which is predicted to truncate the protein or mark the message for nonsense mediated decay (Audo et al., 2011). These mutations disrupt only the long isoform of WHRN.

Mice with a targeted deletion of the long isoform of whirlin have some partial hearing (75 dB SPL) which is non-progressive in nature (Yang et al., 2010) . The inner hair cells stereocilia are unaffected while the outer hair cells stereocilia loose their characteristic "V" shaped formation and assume a "U" shape. Some of the stereocilia are missing from the innermost row in outer hair cells. However, unlike *whirler* mutant mice who are deaf due to a deletion in *Whrn* disrupting both isoforms of the protein, mice with targeted ablation of the long isoform of whirlin do not have abnormally short stereocilia.

Genetics of Nonsyndromic Recessively Inherited

identify genetic modifiers in future.

locus for at least a subset of the participants.

help in identification of genetic modifiers in future.

important for modification of hearing loss.

to treat and cure deafness in future.

**3. Conclusions**

Moderate to Severe and Progressive Deafness in Humans 263

A role of modifier genes in reducing severity of hearing loss is suspected for many other deafness loci as well, especially those showing a wide phenotypic variation in presence of identical genetic mutations. However, currently no locus has been mapped or any gene identified as a potential modifier. Usually each family has few individuals with sufficiently different phenotypes to make gene mapping studies feasible. Using whole genome sequencing approaches in either a small subset of such individuals or in larger families may

*GJB2* is the most widely sequenced deafness genes and mutations in this gene are associated with deafness which is mild in degree to more profound losses. However, it has not been possible to map a genetic modifier which reduces severity of hearing loss using either traditional linkage analysis or association studies. A whole genome association study on DNA of more than a thousand *GJB2* c.35delG homozygous individuals living across Europe and North America regions failed to identify a single locus as a modifier in individuals with mild phenotypes of hearing loss. However, some SNPs with smaller modifying effects on the phenotype were identified (Hilgert et al., 2009). It is possible that a more stringent ethnic definition and data re-analysis in a smaller group may succeed in mapping a single

The unavailability of different cell types derived from inner ear tissues in humans have inhibited direct evaluation of modifier genes in hearing loss by transcriptional analysis as for other disorders such as spinal muscular atrophy (Oprea et al., 2008). However, induced pluripotent stem cell lines can be derived from more and less severely affected deaf individuals respectively. These could be then differentiated *in vitro* into the relevant cochlear cell types followed by comparison of their mRNA expression profiles. This may

Modifiers of hearing loss identified in mice may also be eventually found to be implicated in humans. Currently, only two genes have been identified which result in complete rescue of hearing defects in mice. For example alleles of *Cdh23* and *Mtap1a* can rescue hearing loss in mice with mutations in *Atp2b2* and *Tub* respectively (reviewed by Yan & Liu, 2010). Targeted sequencing of these genes in humans may also identify comparable variants

Genes and loci continue to be identified in aetiology of moderate to severe and progressive deafness. Current research has revealed that different alleles of a deafness gene can cause less severe hearing loss or more profound deafness. Further work needs to be carried out to identify additional loci and genes for progressive deafness and those for less severe hearing loss phenotypes as well as modifiers in the genetic background that suppress or enhance hearing loss. The contribution of different genes to moderate to severe and progressive hearing loss also needs to be studied in different world populations. Additionally, it remains important to document hearing loss in families which have already been described to suffer from moderate to severe hearing loss in order to check for progression of hearing loss in future. Strategies need to be evolved for identification of modifiers which will elucidate molecular pathways involved in normal hearing. This may be of help in designing strategies

#### *CLRN1 (USH3A)*

The deafness phenotype associated with USH3 involves postlingual, progressive hearing loss. The time of onset and severity of hearing loss can be highly variable (Ness et al., 2003). So far only one gene, *CLRN1* has been identified which causes an USH3 phenotype (Joensuu et al., 2001). In contrast to other world populations, mutations in *CLRN1* are a frequent cause of Usher syndrome in the Finnish population. *Clrn1-/-* mice have early onset hearing loss and are profoundly deaf by P30 (Geng et al., 2009). *Clrn1-/-* mice have demonstrated that CLRN1 is important for normal maturation of hair cells as well as the afferent nerve synapses. Absence of CLRN1 in mice leads to gradual loss of outer hair cells and supporting cells which is most severe at the basal turn of the cochlea (Geng et al., 2009).

CLRN1 is a small 232 amino acid transmembrane protein which is present at both the basal and apical poles of the hair cells with expression being higher in outer hair cells as compared to the inner hair cells (Geng et al., 2009; Zallocchi et al., 2009). *Clrn1* is also expressed in the spiral ganglion (Geng et al., 2009; Zallocchi et al., 2009). In mice, CLRN1 cannot be detected at the apex of hair cells at P1 and continues to be expressed in both the pre- and post-synaptic regions of outer hair cell type I afferent ribbon synapses (Zallocchi et al., 2009). Additionally, CLRN1 may also have a role in actin assembly (Tian et al., 2009) and intracellular vesicle transport (Zallocchi et al., 2009).


**1. Introduction**

Conventionally, emotion and cognition are understood to be independent system. Researches in the areas of cognition, emotion and neurobiological sciences have shown that the relationship between cognition and emotion is both interdependent and extensive. This close link between emotion and cognition leads to a number of insights that have the potential to inform and transform educational practices at all levels from the classroom to the curriculum to educational policy [1]. The application of emotive cognition strategies in teaching develop strong inter-relationship

between teachers and learners. It triggers cognitive functions on learning and creates conducive meaningful learning behavior among learners. Emotions play an important role in every cognitive function. The cognitive processes are sensitized, focused, energized, focused, broadened and sharpened by the emotions. Application of emotive cognition strategies in the classroom teaching and learning facilitate meaningful learning among learners. However, deeper understanding is needed in teacher education programme that how student-teachers' emotive cognition behavior enhance their meaningful learning.

A critical consideration of quality teacher education programme for 21st century requires vigorous practice of emotive cognition strategies application in teaching develops meaningful learning among student-teachers, and it also builds cognitive competencies such as perception and attention, memory and learning, knowledge, decision making, problem solving ability, inter-personal skills and intra-personal skills among the future teachers. So undergraduate teacher education programme required proper implementation of emotive cognition strategies on enhance meaningful learning behavior among student-teachers.

### **1.1 The regulation of emotions in learning**

Emotions show a systematic function in learning and it directly influences the process of learning. For instance, emotions like joy, enthusiasm, and passion gives energy to learners to learn a new or difficult concept in a perfect manner; at the same time emotions like fear, stress, aggression and anxiety create discomfort to the learners. It also disturbs them mentally as well as physically.

In the center of the human brain, the limbic system is present. It consists of the amygdala and hippocampus, historically called the "emotional brain". Amygdala plays an important role in survival situations and those situations it alerts the body. It stores the primitive emotions of sadness, fear, aggression and joy. It is also associated with emotional memories storage. The hippocampus stores short-term memory as well as the long-term memory. The cognitive function of amygdala is due to the activation of emotional regulation. Hippocampus performs information storage and retrieval functions.

Some two thousand years back Plato pronounced "all learning has an emotional base", whereas, present facts whole together emphasize that each one's emotions do re-sculptour neural tissue, Organization for Economic Co-operation and Development (OECD) [2]. Both neurobiologists and educational experts identify learning as an amalgamation of psychological, and emotional cognitive process. All of these three elements are interdependent and inter laced in each of the experience concerning learning. It impacts the functioning of the brain function at the time of learning.

In the learning process, emotions are deemed to a strong as well as an integral part, in day-to-day life. A successful learning takes place when a learner handles his emotions during the learning process. Emotional regulation has an undeviating impact on the process of cognition like the capacity to focus attention, problem solving approach and recovery of memory [3]. Appropriate emotional regulation maintains the functions of cognition to accomplish the goals of the learning process.

The anxiety or stressful emotions make a huge impact both on memory as well as learning process. Studies conducted on brain implied that negative emotions form a sort of hurdle to learning. The parts of the brain such as amygdala, the hippocampus and stress hormones of glucocorticoids, epinephrine and norepinephrine play a vital

#### *Perspective Chapter: Emotive Cognition Strategies on Enhancing Meaningful Learning… DOI: http://dx.doi.org/10.5772/intechopen.111885*

role in moderating the impact of negative emotions namely, fear and stress both on learning and memory [4]. Simultaneous bodily events such as increased heart rate, perspiration, and elevated adrenaline levels also occur [5, 6], and in turn influence cortical activity. Some level of stress is essential for optimal adaptation to face environmental challenges and lead better cognition and learning, but beyond this modicum it can be damaging, both physically and mentally. When students face negative situations in their teaching-learning process it triggers either fear or stress there by affecting their cognitive functions during their learning.


**11.1 PD-1 inhibitors**

PD-1, also known as CD279, is a CD28 family member expressed on lymphoid cells such as T cells, B cells, and natural killer (NK) cells, as well as on myeloid cells [60]. The binding of PD-1 on T cells with the ligands PD-L1 or PD-L2 suppresses signals downstream of T-cell receptor activation in the context of antitumor immunity [61, 62]. The monoclonal antibody that target the programmed death-1 receptor is Pembrolizumab, which is a humanized monoclonal antibody directed against PD-1.