Psychological statements—Direct questions.
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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
\n\n\n\n\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"2169",leadTitle:null,fullTitle:"Game Theory Relaunched",title:"Game Theory Relaunched",subtitle:null,reviewType:"peer-reviewed",abstract:"The game is on. 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The field will evolve in the near future with the use of new delivery platforms, while various technologies will merge into more concrete media, including wearable multipurpose devices. 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The diffusion and market penetration of new technologies are becoming a crucial point for transport system analysts and decision-makers. The main issues are regarding a correct understanding of the phenomena and the simulation of different possible operational scenarios.
Among the several new technologies aiming to let the transportation system be more efficient and sustainable, two main issues continue to be challenging tasks: (a) interpreting and modeling users’ behaviour towards these new technologies and (b) assessing the potential environmental impacts.
Both issues are highly correlated as, without an effective interpretation of users’ behaviour, no reliable estimation of the market penetration, and/or the corresponding impacts could ever be obtained.
Within the cited context, the consumer choice theory based on the random utility theory (RUT) may be considered the more effective and practical approach to model and forecast user’s behaviour, but it is a common opinion that consolidated random utility model (RUM) formulations may lead to neglect the numerous nonquantitative factors that may affect users’ perceptions and behaviors. As a matter of fact, psychological factors, such as attitudes, concerns and perceptions, may play a significant role which should be explicitly modeled. On the other hand, collecting psychological factors could be a time- and cost-consuming activity. Furthermore, real-world applications must rely on theoretical paradigms easily implementable in order to allow the estimation of users’ choices in different technological scenarios.
As clearly stated in the current literature, the propensity to adopt a new technology, and, in particular, an alternative fuel vehicle (AFV), is mainly affected not only by instrumental attributes of the technology of interest (alternative) and of the competing technologies (other alternatives) and by personal attitudes (attitudes) of the consumer (user) not depending on the alternatives but also on the consumer personal feelings and on the socioeconomic context in which he/she lives. Several recent analyses have pointed out the necessity to take into account attributes considering the perceptions and the attitudes of the users. For example, see [1]. The main issues of the literature refer to:
How to better collect information about users’ attitudes, concerns and/or perceptions; an “ad-hoc” survey aiming to “collect” attitudes/perception needs to be designed.
The assessment of the methodology to be pursued in accordance with the RUT [2, 3, 4, 5], which is the richest and by far the most widely used theoretical paradigm for modeling transport-related choices and, more generally, with discrete choice modeling (i.e. models representing choices made among discrete alternatives).
Indeed, even though RUMs models usually adopted in demand modeling are suitable for the representation of the choice process, these are not applicable to represent the perceptions and attitudes [6]. The issue was addressed in the literature through the hybrid choice models (HCM) [7, 8, 9, 10, 11] based on attitude investigations trying to infer the role of psychological factors with latent variables within a discrete choice modeling framework.
In particular, several studies aiming to overstep the boundary of RUMs have been conducted by Ortúzar and Hutt [12] and by McFadden [13], which around the 1980s investigated the possibility to include subjective variables in a discrete choice modeling. Starting from the approach proposed by Jöreskog [14] focusing on the investigation between latent variables and the measurement of the perception indicators, several researchers contributed to the assessment of the methodological framework of hybrid choice models (e.g. see [15, 16, 17]).
The book chapter is organized as follows: Section 2 focuses on modeling overview, while Section 3 focuses on survey design; the quantitative preliminary analyses and the model specification are, respectively, discussed in Sections 4 and 5. The corresponding results of two case studies are displayed and discussed in Sections 2 to 5.
The HCM based on RUT is a discrete choice model which integrates and simultaneously estimates different types of sub-models into a unique structure. If the HCM includes a latent variable model, it is possible to take into account the effects of users’ latent attitudes, perceptions and concerns (i.e. integrated choice and latent variable (ICLV) model).
Adopting the standardized notation for path analysis, Figure 1 introduces the general structure of an ICLV and allows to comprehend the different sub-models that define an ICLV: the latent variable model and the discrete choice model. In particular, the ellipses represent the unobservable (latent) variables, the rectangles represent the observable variables, and the circles represent the error variance or disturbance terms.
Scheme of a hybrid choice model (HCM).
Since the latent variables (attitudes, perceptions and concerns) cannot be directly observed and measured from a revealed choice or a stated preference experiment [18], they have to be modeled and then indirectly identified starting from a set of indicators. The latent variable model allows to identify and measure these unobservable variables as a function of the indicators, in order to include them in a choice model.
Mathematically, a latent variable is treated as a random variable; the latent variable is specified through a
Finally, in accordance with the RUT, the utility
One of the main issues in the specification of an ICLV model consists of the observation and the measurement of the attitudes/concerns/perceptions. The survey design is a crucial part since it should allow to characterize the respondents, to come up with respondents’ attitudes/concerns/perceptions and to measure them.
Usually, a survey is structured in different subsections aiming to collect various information from the respondents. First, (a) socioeconomic and (b) household characteristics have to be inquired; then specific sections aimed to capture users’ attitudes, concerns and perceptions should be specifically designed, for instance, (c) the users’ attitudes and concerns that may influence the willingness to adopt/use/purchase a new technology and (d) the users’ perceptions with regard to the advantages and disadvantages of the technology under investigation. Finally, it is necessary to collect (e) the users’ propensity to adopt/use/purchase a new technology. In this case, different scenarios (usually not real but realistic) should be carefully designed in order to cover the possible range of the involved decisional variables.
Even though the literature is consolidated on survey design with respect to Sections (a), (b) and (e), Sections (c) and (d) need to be specifically discussed.
As introduced before, one of the main issues related to the specification and estimation of an HCM relies on how to collect users’ attitudes (to observe and quantify them). Since attitudes are entities constructed to represent certain underlying response tendencies, they cannot be measured directly, but they could be inferred by studying behaviour which, in turn, might be reasonably assumed to indicate the attitudes themselves.
The behaviour may be one that occurs in a natural setting or in a simulated situation. In general, different approaches to measure attitudes may be pursued:
This method has two approaches to question the individuals:
In general, direct questioning is the most pursued approach since it allows to control the investigated context and requires smaller times and costs. The method application requires the scale of measurement definition. Although the literature has proposed different scales as Thurstone, Likert and Bogardus, the Likert scale [19] has the most flexible, robust and easy to implement scale of measurement.
Latent variables may be classified as attitudes [20, 21], perceptions [22] and concerns [23]:
Within the aforementioned conceptual framework, it is suggested to design a direct questioning survey considering two different types of questions to be submitted to the respondents: direct and indirect questions. An overview of two examples of survey design is provided in the following.
A first example refers to the HySolarKit [26] case study. The questionnaire described in this section was designed [24] to investigate the role of latent factors in the choice of a new automotive technology which aims to electrify/hybridize existing vehicles through an aftermarket kit which can be recharged by the grid but also by solar power (the HySolarKit). The experiment was applied to the case study of the Salerno municipality which is the capital city of Salerno province (region of Campania, southern Italy).
The first section of the questionnaire aimed to collect users’ socioeconomic, activity-related attributes and household-vehicle characteristic information; therefore, respondents were provided with direct and indirect questions.
In particular, direct questions were about fuel consumption, vehicle reliability, vehicle design and the environmental impact; indirect questions were about three main latent behaviors: the fuel consumption, the vehicle design and the environmental impact. A detailed description is displayed in Tables 1 and 2.
Indicator | Statement |
---|---|
Qcons | The vehicle fuel consumption significantly influences my choice in purchasing a new car |
Qrel | The vehicle reliability significantly influences my choice in purchasing a new car |
Qdesign | The vehicle design significantly influences my choice in purchasing a new car |
Qenv | The evaluation of the environmental impact significantly influences my choice in purchasing a new car |
Qprice | The price significantly influences my choice in purchasing a new car |
Psychological statements—Direct questions.
Indicator | Statement |
---|---|
Icons1 | The consumption and the energy class significantly influence my choice in purchasing an appliance |
Icons 2 | I am usually attentive to the special offers of electric operators |
Icons 3 | My home bulbs are energy efficient |
Icons 4 | I usually evaluate the car efficiency with respect to the car cost mileage |
Icons 5 | I normally compare the fuel prices among different petrol stations |
Icons 6 | When driving I am not willing to behave to reduce the environmental impacts (my driving behaviour is normally aggressive) |
Indicator | Statement |
Idesign1 | When parking I am usually careful to avoid having my car damaged |
Idesign2 | I often read journals of design |
Idesign3 | When furnishing I am willing to buy pieces with modern design features and original details |
Idesign4 | I am willing to go to the body shop mechanic not only for major damages |
Idesign5 | I am willing to install not standard equipment (such as antitheft block shaft) on my own car |
Indicator | Statement |
Ienv1 | I often control the exhaust/emission system of my car |
Ienv2 | In consciously make the separate waste collection |
Ienv3 | I really enjoy spending my free time in parks and green areas to breathe clean area |
Ienv4 | How much do you agree with following sentence: We must act and make decisions to reduce emissions of greenhouse gases |
Ienv5 | How much do you agree with following sentence: The government should invest in low energy impact |
Ienv6 | I am not willing to use the car during weekend to protect the environment and then reduce air pollution |
Psychological statements—Indirect questions.
The questionnaire was completed through a second section based on installation cost scenarios. In particular, each respondent was faced with two scenarios based on different installation costs (ranging from 500 to 4000 €).
Respondents were provided with a brief description of the technology and its main characteristics: how it works, how it is installed, the different performances (e.g. power, acceleration, speed), the environmental and fuel consumption benefits that can be achieved and the operating time. A brief overview is displayed in more detail in Table 3 [27].
Overview of the two alternatives in the choice context.
The second example was about electric vehicle (EV) market penetration [28]. The questionnaire was designed with the aim to investigate the different attributes/determinants that may influence the decision to purchase an electric vehicle.
The first section of the questionnaire aims to gather information about the users’ socioeconomic characteristics, the characteristics of the owned household vehicles and the psychometric indicators of the latent variables. Particularly, two types of attitudes and two types of perceptions were inquired. The investigated attitudes were towards the environment and about the vehicle’s technical features, while the investigated perceptions referred to the advantages and disadvantages of electric vehicles that may affect users’ willingness to purchase them. To this end, several direct/indirect questions were specifically designed adopting a five-point Likert scale (ranging from strongly disagree to strongly agree). The psychological statements used as indicators of those unobservable latent variables are detailed in Table 4.
Indicator | Statement |
---|---|
The vehicle fuel consumption significantly influences my choice in purchasing a new car | |
I care about the amount of pollution generated by a car when it’s being used | |
Indicator | Statement |
The vehicle technical features significantly influence my choice in purchasing a new car | |
I prefer driving a car with a powerful engine | |
When I am choosing a car, I find myself spending a lot of time checking out differences in terms of top speed (km/h) | |
The immediate acceleration increases my driving pleasure | |
The vehicle range is very significant with respect to my mobility needs in everyday life | |
Indicator | Statement |
I am interested in EV to contribute to the emissions reduction | |
Compared to a normal car, EV are superior in terms of energy efficiency | |
I believe using EV can significantly reduce the acoustic pollution in cities | |
I prefer having a car with less moving parts | |
Indicator | Statement |
DISinfr | When driving an EV, I would always be worried about the lack of charging points |
DISred_fea | Compared to a normal car, EV are inferior in terms of performances |
DISbatt_range | The low range of the battery is a real disadvantage |
Psychological statements of the survey.
The second section of the questionnaire contains the users’ choice behaviour in buying a new car. To this end, a Renault Zoe as the electric alternative and a diesel-fuelled Renault Clio are considered as conventional vehicles (CV).
These two alternatives were compared in terms of their technical features and then hypothesized that the interviewee has a budget enough to buy a new car to be used in urban areas. The monthly cost of buying and fuelling the conventional vehicle is calculated, considering 8-year monthly payments to buy it and an estimated fuel cost to drive it for 10,000 km per year. This results in a total cost of 192 € per month (Table 5).
Comparison of the two alternatives in the choice context.
After the comparison, each respondent was faced with five monthly cost scenario setup for the electric vehicle. They started from the same value calculated for the diesel vehicle (i.e. 192 €/month), and then it was considered that the EV would have cost 10, 20, 30 and 40% more (€211, €230, €250 and €270 per month, respectively).
In the case of HCM, descriptive and statistical analyses of the collected answers regarding the perception indicators are necessary for two main reasons: firstly, they allow supporting the soundness of the experimental design setup; secondly, they allow deriving first correlations between observed behaviour, collected attributes and investigated attitudes/perceptions/concerns. Therefore, results from preliminary analyses may give important insights on the survey robustness and a useful guidance for the model specification. In general, the analyses may be divided in basic preliminary analyses based on the analysis of
The Cronbach’s alpha, α (or coefficient alpha), is a measure of the internal consistency (or reliability) of the responses to multiple questions that are meant to measure a specific latent variable in a survey using a Likert scale. This indicator aims to tell whether the survey was accurately designed, and the questions were not answered randomly.
For each latent variable, it is necessary to have at least two indirect questions. The higher the number of questions, the better the latent variable would be measured. These questions, if possible, should be a mix of “+keyed” and “-keyed”, depending if each one is positively correlated to the latent variable or negatively (Table 6).
Scoring | Very inaccurate | Moderately inaccurate | Neither inaccurate nor accurate | Moderately accurate | Very accurate |
---|---|---|---|---|---|
+ keyed | 1 | 2 | 3 | 4 | 5 |
− keyed | 5 | 4 | 3 | 2 | 1 |
Scores for a five-point Likert scale.
When a survey intends to measure more than one latent variable, it is recommended to alternate their questions. This strategy combined to the mix of “+ keyed” and “− keyed” is employed in order to encourage respondents to be more aware of each item and the response provided and, therefore, increases the probability of gathering valid responding. If not, respondents may realize which latent variable is being measured, and they might tend to answer with the same response if the questions are all equally keyed. In this case, the total variance will be lower, and the relation with other variables in the study will be underestimated.
The Cronbach’s alpha is calculated for each group of questions that measure a specific latent variable. Given
where:
A rule commonly accepted to interpret the values of Cronbach’s alpha when used with a Likert scale is (Table 7):
Cronbach’s alpha | Internal consistency |
---|---|
0.9 ≤ α | Excellent |
0.8 ≤ α < 0.9 | Good |
0.7 ≤ α < 0.8 | Acceptable |
0.6 ≤ α < 0.7 | Questionable |
0.5 ≤ α < 0.6 | Poor |
α < 0.5 | Unacceptable |
Scales of values for the Cronbach’s alpha.
An easy quantitative/qualitative analysis to perform on the data collected consists of calculating the mean value and the standard deviation of the responses to the Likert scale for each question and then evaluating whether the responses are consistent (they have a low deviation) or if the mean value corresponds to the one expected.
Given
In matrix terms
where
Assuming that:
Any solution for the unknown values
With these assumptions, the variance of
where
Given two variables,
The covariances can be calculated as
This shows that the covariance of two variables is equal to the scalar product of their loadings.
With the expressions in Eqs. (5) and (7), it is possible to construct a
To extract the first set of loadings and factors from the observed variables, there are different methods. However, principal component analysis (PCA) and common factor analysis (CFA) are the most preferred and most used:
This model can be written as
This model can be set up as
Once the factors are extracted, their eigenvalues (or characteristic roots) provides the amount of variance explained by every factor out of the total variance. Then, the number of factors is reduced by retaining only those which have an eigenvalue larger than 1, according to Kaiser’s criterion [29].
The factor loadings obtained represent the amount of variance explained by the variable on every factor. In structural equation modeling, a value of 0.7 or higher represents that the factor extracts sufficient variance from that particular variable.
The loading values may be hard to interpret at a first glance. So, in a second step of the analysis, the loadings obtained can be “rotated” in order to arrive at another set of loadings, which renders the values more understandable, while fitting the observed variances and covariances equally. The effect of rotating the factors produces that each variable loads more strongly only on one of the factors and weakly on the other factors, producing the eigenvalues to vary.
There are several rotation methods that provide different solutions, arising to different interpretation. The interpretation of each factor and the number of factors needed are very subjective, and the researcher has the task to identify what is the meaning of each factor (i.e. which is the unknown latent variable hidden in the indicators).
From a general point of view, the rotation methods can be subdivided in orthogonal (when the factors cannot correlate) or oblique (the factors are allowed to correlate). The most common methods within each one of two groups are listed below:
Orthogonal methods
Oblique methods
An overview of the preliminary statistical analysis for the electric vehicle case study1 introduced in Section 3.2 is provided. The proposed example includes analysis of Cronbach’s alpha, mean and standard deviations, factor analysis with principal components as the extraction method and rotated component matrix using the Varimax method.
First of all, it may be observed that Cronbach’s alpha is not consistent for all answers; therefore, the survey reliability is confirmed only in the case of psychological statements referred to the environment, the technical features and the EV’s advantages (i.e. Cronbach’s alpha is higher than 0.5). Among them, a further analysis is provided in terms of mean and standard deviations: with respect to the attitude about the environment, for both statements the mean is higher than 3, and the standard deviation is lower than 1; regarding the attitude about technical features, higher values of mean (higher than 3) and lower values (lower than 1) of standard deviations are observed for the following statements (refer to Section 3.2 for the meaning of the following variables): <
SD | ||
2.98 | 0.85 | |
3.01 | 1.14 | |
SD | ||
4.21 | 0.82 | |
3.25 | 0.94 | |
4.05 | 0.87 |
Mean and standard deviations of the responses in the EV study.
The factor analysis carried out through the principal component analysis extraction method, allowed to identify the latent factors correlated to the psychological statements. The components extracted were also rotated using the Varimax method.
The results (significant values are highlighted in bold in Table 9) underline the correlations among the following statements referred to the advantage perceptions <
1 | 2 | 1 | 2 | |
---|---|---|---|---|
AD_red_CO2 | −0.306 | 0.125 | ||
AD_red_poll | −0.018 | −0.156 | ||
AD_efficiency | −0.532 | 0.305 | ||
F_consumption | 0.548 | −0.068 | ||
F_pollution | 0.352 | 0.188 |
Factor analysis of the EV study.
The utility choice function in the hybrid choice model is based on the assumption that each individual is faced with a set of alternatives,
With reference to the
In particular, if
where
Furthermore, let
where
The psychometric indicators that reveal the latent variables may be coded using a Likert scale [19]. These indicators can be considered to be a linear continuous expression of the LV’s or an ordered discrete variable. The first approach has been historically chosen because simpler and more practical with lower computational cost. However, assuming these indicators as continuous variables are in contrast with the real nature of the Likert scale (the Likert scale is a discrete measure) [30], such an approach may introduce some biases in the parameters’ estimation. In recent years, several studies have treated them as discrete variables, but with a higher computational cost [31]. In particular, if the measurement is represented by an ordered discrete variable
where
If the measurements use a Likert scale with M = 5 levels, four parameters
Then, the probability of a given response
For completeness, in the following section, the estimation results related to the HySolarKit and the electric vehicle case study are shown.
In this research report, the model parameters were estimated in accordance with the maximum simulated likelihood statistical approach.
The first results shown in this section refer to the HySolarKit case study. As already anticipated in Section 3.1, the choice set was composed of two alternatives: “install” and “not-install”. In the following the estimation results are presented, distinguishing the choice utility function, the structural equations and the measurement equations.
The utility choice functions were analytically specified in accordance with the following equation:
The results are shown in Table 10. In particular, the estimation results underline the following latent variables as statistically significant: attitudes towards fuel consumption (LV1), towards the vehicle design (LV2) and towards the environment (LV3).
Age | +0.160 | |
Master’s degree | + 0.156 | |
ZonRes | +0.0761 | |
CarAge | +0.0272 | |
by Car-Shopping | +0.669 | |
by Car-Personal Services | +0.192 | |
Δcost | +0.0638 | |
LV1 | +0.548 | |
LV2 | +0.0682 | |
LV3 | +0.104 | |
Statistics | ||
Number of respondents | 1364 | |
Number of observations | 1364 | |
Init-log-likelihood1 | −944.760 | |
Final log-likelihood | −779.81 | |
Rho-square | 0.212 |
Attribute coefficients of the choice model. HySolarKit case study.
in parenthesis the t-test values.
Only the log-likelihood associated with the discrete choice component is considered.
The coefficients related to the parameters in the measurement equation for an ordinal specification are estimated in the considered model. As the measurements are using a Likert scale with seven levels, six parameters
DELTA1 | + 1.46 |
DELTA2 | + 1.34 |
DELTA3 | + 1.52 |
Delta values of the calibrated measurement equations. HySolarKit case study.
in parenthesis the t-test values.
The coefficients in the structural model are analytically represented by the following equation:
This equation shows that each latent variable is a function of an intercept value
The estimation results displayed in below refers to the significant latent variables of the model, representing the attitude towards the fuel consumption (LV1), the vehicle design (LV2) and the environment (LV3) (Table 12).
Structural model | |
---|---|
−2.32 | |
ω1 | +0.787 |
by car-shopping | −0.448 |
by car-personal services | +0.550 |
Master’s degree | +0.128 |
−3.39 | |
ω2 | +0.299 |
Age | −0.0955 |
SE_male | −0.278 |
— | |
ω3 | +1.34 |
Age | −1.06 |
SE_male | −1.12 |
Coefficients of the calibrated structural model. HySolarKit case study.
in parenthesis the t-test values.
Finally, with regard to the measurement model depending on the perception indicators, they are analytically represented by the following equation:
where each perception indicator is a function of an intercept value
Table 13 shows the coefficients for each perception indicator, which were specified in accordance with the preliminary analyses (not shown for the sake of brevity). In particular, the first latent variable about fuel consumption (LV1) is described by two indicators <
Measurement model | |||||
---|---|---|---|---|---|
Icons0 | Idesign0 | Ienv0 | |||
α 10 | +0.567 | α 20 | −1.79 | α 30 | −1.89 |
λ 10 | +0.725 | λ 20 | +0.148 | λ 30 | +0.495 |
ν10 | +0.787 | ν20 | +1.38 | ν30 | +1.18 |
Icons2 | Idesign1 | Ienv3 | |||
α 12 | 0 | α 21 | 0 | α 33 | −1.36 |
λ 12 | 1 | λ 21 | 1 | λ 33 | +0.729 |
ν12 | 1 | ν21 | 1 | ν33 | +0.983 |
Idesign3 | Ienv4 | ||||
α 23 | +2.79 | α 34 | 0 | ||
λ 23 | +1.60 | λ 34 | 1 | ||
ν23 | +1.43 | ν34 | 1 | ||
Idesign4 | Ienv6 | ||||
α 24 | +2.79 | α 36 | −1.95 | ||
λ 24 | +1.84 | λ 36 | +0.396 | ||
ν24 | +1.65 | ν36 | +1.13 |
Coefficients of the calibrated measurement model. HySolarKit case study.
in parenthesis the t-test values.
In general, the estimation results underline the necessity to introduce two different kinds of questions: direct and indirect questions.
As described in Section 3.2, the considered choice set is composed of two alternatives: the alternative A representing the respondent’s willingness to buy an electric vehicle and the alternative B corresponding to the willingness of buying a conventional (diesel) vehicle. The provided results are referred to an ordered model specification.
In the following the estimation results are presented, distinguishing the choice of utility function, the structural equations and the measurement equations.
The attribute coefficients in the utility choice function are analytically specified by the following equation:
The results are shown in Table 14. In particular, the following attitudes were statistically significant: the attitudes towards the environment (LV1) and the perception of the advantages of EVs (LV2).
VAR_monthly_cost_abs | ||
SE_AutoSI | ||
F_tech_fea [5] | ||
DIS_red_fea [5] | ||
LV_1 | ||
LV_2 | ||
Statistics | ||
Number of respondents | ||
Number of observations | ||
Init-log-likelihood1 | ||
Final log-likelihood | ||
Rho-square |
Attribute coefficients of the choice model. EV case study.
in parenthesis the t-test values.
Only the log-likelihood associated with the discrete choice component is considered
The coefficients related to the parameters in the measurement equation for an ordinal specification are estimated in the considered model. As the measurements are using a Likert scale with five levels, four parameters
DELTA1 | 0.531 |
DELTA2 | 1.27 |
Delta values of the calibrated measurement equations. EV case study.
in parenthesis the t-test values.
The coefficients in the structural model are analytically represented by the following equation:
The estimation results displayed in Table 16 refer only to the two significant latent variables of the model, standing for the attitudes towards the environment (LV1) and the perception of the advantages of EVs (LV2). In particular, for each latent variable, the table displays the results of the intercept value
Structural model | |
---|---|
+1.83 | |
ω1 | +0.119 |
SE_male | −0.242 |
+0.857 | |
ω2 | +0.584 |
SE_male | −0.0445 |
SE_delta_age | −0.0246 |
Coefficients of the calibrated structural model. EV case study.
in parenthesis the t-test values.
Finally, the measurement model depending on the perception indicators is analytically represented by the following equation:
These parameters were specified in accordance with the preliminary analyses. In particular, the first latent variable about the environment (LV1) is described by two indicators, <
Measurement model | |||
---|---|---|---|
α 10 | −4.62 | α 20 | +0.391 |
λ 10 | +2.85 | λ 20 | +1.32 |
ν10 | +1.03 | ν20 | +0.742 |
α 11 | 0 | α 21 | −0.143 |
λ 11 | 1 | λ 21 | +0.881 |
ν11 | 1 | ν21 | +1.22 |
α 22 | 0 | ||
λ 22 | 1 | ||
ν22 | 1 |
Coefficients of the calibrated measurement model. EV case study.
in parenthesis the t-test values.
Depending on the context, several factors may affect users’ choices. In this chapter, the main focus refers to modeling users’ propensity to choose/adopt a new/innovative technology. This is a crucial task in order to increase the attractiveness of strategies that may be employed to achieve sustainable transportation. In particular, two related main issues are still open in the literature: (a) interpreting and modeling users’ behaviour towards these new technologies and (b) assessing the potential environmental impacts. It is widely recognized that traditional approaches used to interpret and model users’ choice behaviour may lead to neglect the numerous nonquantitative factors that may affect users’ behaviors. Indeed, users’ choices may be influenced by social and psychological factors, symbolic and affective factors, habits and the conflict between collective and individual interests (e.g. car use as a commons dilemma). These imply that changes in transportation modes may be achieved either by influencing individual motivations and perceptions (
The book chapter provides an overview of the methodology to be adopted in order to support psychological-based strategies. In fact, psychological factors, such as attitudes, concerns and perceptions, may play a significant role which should be explicitly modeled.
Although several approaches may be identified in the literature able to address the above-mentioned issue, the hybrid choice modeling approach based on RUT can be considered a proper solution to explicitly consider the perceptions, attitudes and concerns in the modeling of the choice behaviour. The specification of such models requires a careful survey design, rigorous preliminary descriptive analyses and the model parameter estimation. The present chapter deals with all the cited issues, first introducing the main criticalities in modeling choice behaviour in new technological contexts, then proposing a methodological framework and finally introducing different explanatory examples on real case studies. In particular, Section 3 focuses the attention on the different approaches to collect users’ attitudes/perceptions and concludes the need for a mixed approach based on both direct and indirect questioning. Section 4 introduces the methodology to properly evaluate the consistency of the dataset and the latent variables identification. It evidences the need for basic analysis, such as the estimation of the mean and standard deviations, and the importance of the Cronbach’s alpha test and the principal components and the rotate component matrices for the identification of the latent variables. Section 5 deals with the model’s specification issues, pointing out the most robust approach for the specification and calibration of a hybrid choice model with latent variable. All the introduced sections are supported by real experimental results [24, 25] for explanatory and guideline purposes.
This research was partially supported by the University of Salerno, under local grant no. ORSA171328—2017.
No potential conflict of interest was reported by the authors.
Very large-scale studies of protein ubiquitination have been conducted over the past two decades. Ubiquitin modification is mediated by three types of enzyme activity, mediated out by E1 ubiquitin-activating enzymes (UBA; also referred to as UAE or E1 enzymes; EC 6.2.1.45), E2 ubiquitin-conjugating enzymes (UBC; also termed E2 ubiquitin-carrier proteins or E2 enzymes; EC 2.3.2.23), and ubiquitin-protein ligases (E3 enzymes). To better understand the molecular mechanisms underlying ubiquitin modification, this review focuses on the structural interactions between ubiquitin modification enzymes and their functions.
Ubiquitin is a small, highly conserved 76 amino acids polypeptide found throughout eukaryotic cells, that modifies cellular proteins. Two mammalian ubiquitin genes,
Ubiquitin-like proteins (UBLs) do not share sequence homology with ubiquitin but also function as protein modifiers. A number of UBLs have been reported, including SUMO1/SMT3, SUMO2–4 [2, 3, 4], Neural-precursor-cell-expressed developmentally downregulated protein-8 (NEDD8)/RUB1 [3, 5, 6], ISG15 [6, 7], ATG8/APG8 [8], ATG12/APG12 [9], URM1 [3], and homologous to ubiquitin 1 (HUB1) [10]. During protein modification by ubiquitin and UBLs, specific activating, conjugating, and ligase enzymes, catalyze attachment of the modifier to target proteins. Similar to ubiquitin, UBLs are also produced as precursors, and deubiquitinating enzymes expose their C-terminal glycine residues to activate them, although HUB1 lacks a C-terminal diglycine sequence.
The SUMO-1 protein has only 18% sequence identity with ubiquitin, but contains the ββαββαβ fold structure characteristic of the ubiquitin protein family [2]. The hydrophobic cores of SUMO-1 and ubiquitin are similar; however, the overall charge surface topology of SUMO-1 differs significantly from that of ubiquitin or other UBLs [2, 11]. The selective modifications mediated by the four SUMO homologs, SUMO-1, SUMO-2, SUMO-3, and SUMO-4 [12, 13, 14, 15, 16], remain to be determined. In addition, SUMO has an N-terminal extension (approximately 20 amino acids) not present in ubiquitin, which is required for SUMO function [17]. A consensus motif and lysine residues involved in SUMOylation are present in SUMO-2, SUMO-3, and SUMO-4 and well-conserved; however, these SUMO proteins do not have Lys residue counterparts of ubiquitin Lys 48 and 63.
NEDD8 shows 58% sequence identity and 80% sequence similarity to ubiquitin polypeptide. By contrast, the ATG12 sequence is unrelated to that of ubiquitin, and forms a covalent protein complex with ATG5, which is required for autophagy; this reaction requires the C-terminal glycine residue of ATG12 and a lysine residue in ATG5 [18].
The ISG15/ubiquitin cross-reacting protein (
HLA-F adjacent transcript 10 (FAT10; also known as ubiquitin D) also bears two ubiquitin-like domains. HUB1 has only 22% sequence identity with ubiquitin and possesses an invariant C-terminal double-tyrosine motif, unlike the double glycine residues present in ubiquitin and other UBLs [25].
E1 UBA enzymes adenylate the C-terminal glycine residue (Gly 76) of ubiquitin polypeptides, coupling them with ATP. The C-terminal ubiquitin polypeptide glycine residue is linked to AMP via an acyl-phosphate bond, and the adenylated ubiquitin polypeptide is linked with the sulfhydryl side chain of a cysteine residue (Cys 632 in human UBA1) in the E1 enzyme catalytic center. A thioester intermediate (S-ubiquitinyl-(E1 UAE)-L-Cys) is synthesized in this two-step reaction, along with AMP and diphosphate (Reaction (1)).
In human, ten UBA orthologues have been identified that can activate ubiquitin or UBLs. Ubiquitin-like modifier-activating enzyme 1 (UBA1) is mainly responsible for ubiquitin-activation and can also activate the NEDD8 UBL peptide [26, 27, 28]. UBA2 (or UBLE1B) is also known as SUMO-activating enzyme subunit 2 (SAE2), and activates the SUMO UBL peptide as heterodimer with SAE1 [29]. UBA3 (or UBE1C) encodes the NEDD8-activating enzyme E1 catalytic subunit and forms a heterodimer with NAE1 (or APPBP1, an amyloid-beta precursor protein binding protein), which activates NEDD8. UBA5 activates UFM1 (ubiquitin-fold modifier 1) [30], while UBA6 (alternatively UBE1L2) is an E1 enzyme involved in UBL activation [31, 32]. Autophagy related 7 (ATG7) is an E1 enzyme for UBLs including ATG12 and ATG8. NEDD8-activating enzyme E1 regulatory subunit (NAE1 or APPBP1) is an E1 enzyme for NEDD8, along with UBA3 [33]. Ubiquitin-like modifier-activating enzyme 1 Y (UBA1Y) is encoded by the Y chromosome and expressed specifically during spermatogenesis [34, 35, 36, 37]. The UBL, FAT10, is activated by UBA1 and UBA6. UBA7 is induced by interferon-α and β and involved in ISG15 induction.
UBA structures consist of an adenylation domain that interacts with ATP and UBLs, a catalytic domain comprising a Cys residue that binds to UBLs, and a C-terminal ubiquitin fold domain (UFD) required for binding to E2 enzymes.
In a study of mammalian UBA1 with a temperature-sensitive (ts) mutation, cells expressing the ts-UBA1 mutant exhibited cell cycle arrest at the G2/M phase transition, as well as dramatically decreased ubiquitin conjugation [38, 39]. UBA1-knockdown in human cells also leads to reduced cell proliferation [40]. Furthermore, cells expressing the ts-UBA1 mutant show reduced receptor tyrosine kinase endocytosis and degradation [41]. In addition, mice lacking UBA3 are characterized by a mitotic defect in G1/G0 transition, that causes accumulation of SCF ligase targets, including Cyclin E and β-catenin.
E2 UBC enzymes transthiolate activated ubiquitin from S-ubiquitinyl-[E1 UBA] to themselves. A thioester linkage is formed between an E2 UBC and ubiquitin via the C-terminal glycine of ubiquitin, and the sulfhydryl side chain of a Cys residue in the E2 UBC catalytic center [42] (Reaction (2)).
The transthiolation reaction involving S-ubiquitinyl-[E1 UBA]-L-cysteine and E2 UBC is strongly stimulated by occupancy of the nucleotide-binding site by either adenylated ubiquitin or ATP alone [43]. Ubiquitin transfer to the target protein is assisted by E3 ubiquitin ligases. Homologous to E6-AP C-terminus (HECT) domain family E3 ligases transfer ubiquitin to the target via a Cys residue in the E3 ligase. By contrast, Really Interesting New Gene (RING) family E3 ligases transfer ubiquitin directly to target proteins. The properties of specific E2 UBC enzymes determine the ubiquitin moiety and substrate specificity of E3 ligases. Indeed, the specificity of interactions with E2 reflect E3 substrate specificity. Amino acids surrounding the Cys residue are evolutionarily conserved among E2 UBCs, and referred to as the ubiquitin-conjugating (UBC) domain or the core catalytic domain [44]. The UBC domain folds an N-terminal helix (H1), a four-stranded β-meander structure (S1–S4), a short 310-helix (H2), and three C-terminal helices (H3–H5) [45, 46]. Amino acid sequence variations in the UBC domain contribute to specific interactions with E1 UBAs, E3 ligases, and target proteins [47, 48, 49, 50, 51].
E2 UBCs are divided into four classes based on structural differences [52]: class I E2 enzymes consist of only a UBC domain; class II E2 enzymes contain additional C-terminal extension residues; class III E2 enzymes have N-terminal extension residues; and class IV E2s have both N- and C-terminal extensions. Class II UBC2 and UBC3 proteins have acidic C-terminal extensions, which mediate a preference for binding to basic substrates, including histones [53, 54, 55]. The acidic extension is also required to contact basic canyon residues of the Cul1 subunit of the SCF RING subcomplex (ROC1-CUL1) [56, 57, 58]. UBC6 processes C-terminal extensions, to promote ER localization [59, 60]. Class II UBCs include: E2-25K (yeast UBC1) [61], UBC4 [62], UBCH6, UBCH7 [63], UBE2E1 [64], UBE2E2 [65], and UBE2E3 [66, 67].
UBL-specific E2 UBC enzymes process proteins for ubiquitin-like modification. UBC9 is an E2 UBC enzyme specific for the UBL, SUMO, and binds directly to SUMO substrates through a specific short consensus amino acid motif, Y-K-X-[D/E], where Y is any bulky hydrophobic amino acid, including isoleucine, leucine, or valine; K is the lysine residue which is modified by SUMO; X is any residue; D is aspartic acid; and E is glutamic acid [68]. UBC9 contains N- and C-terminal extension residues within the UBC domain, and non-conserved residues in the H1 helix and the insertion β-sheet (S1/2) are required for both interaction with UBA enzymes and formation of the SUMO-thioester bond [69, 70]. ATG3/AUT1 is a dedicated E2 UBC for ATG8 [71]. UBC12 is an E2 UBC specific for NEDD8, which interacts with the NEDD8 E1 UBA via its UBC domain [72, 73], and includes a unique N-terminal region that docks to the E1 enzyme, UBA3, but not to other UBAs. The E2 for ISG15, UBCH8, takes part in reactions involving both UBEL1, the E1 for ISG15, and UBA1, the E1 for ubiquitin [7].
E3 ubiquitin ligases are also referred to as ubiquitin-protein ligases, E3 ligases, or E3 enzymes. Ubiquitin is covalently bonded to the ɛ-amino group of a lysine residue within the substrate protein via an isopeptide bond. The last step in this binding is mediated by E3 ubiquitin ligases, which determine the substrate specificity by ∼ to target proteins. E3 ubiquitin ligases transfer ubiquitin linked with a UBC to the ϵ-amino group of a lysine residue of the target protein. An isopeptide bond is formed between the C-terminal glycine residue of ubiquitin and an ϵ-amino group of a lysine residue in the target protein.
E3 ubiquitin ligases are divided into three major classes: HECT type (Section 3.3.1), RING-type (Section 3.3.3), and U-box E3 ligases (Section 3.3.4). HECT type E3 ubiquitin ligases form a thioester intermediate with the active-site cysteine of the E3, following the formation of an isopeptide bond between the C-terminal glycine residue of ubiquitin and the ϵ-amino group of a lysine residue in the target protein. RBR-type E3 ubiquitin ligases (Section 3.3.2) mediate similar reactions to HECT type E3 ligases. RING-type and U-box E3 ligases mediate different reactions from HECT and RBR-type E3 ligases, in which ubiquitin is transferred from ubiquitinyl-UBC directly to the target protein without formation of a thioester intermediate. Multi-subunit RING-type E3 ligases (Section 3.3.3.1) form complexes with a scaffold protein and a contain recognition modules that bind to substrates.
HECT-type E3 ligases transfer ubiquitin from an E2 ubiquitin-conjugating enzyme (EC 2.3.2.23) to a cysteine residue in the HECT domain in the C-terminal region of an E3 ligase (Reaction (3)). The activated ubiquitin from S-ubiquitinyl-[E3 ligase]-L-cysteine is transferred from the intermediate to the target protein (Reaction (4)). The C-terminal glycine residue of the received ubiquitin is linked with the ε-amino chain of a lysine residue of the acceptor protein, forming an isopeptide bond. Importantly, the HECT domain forms a thioester intermediate with ubiquitin, unlike other E3 ligases.
HECT type E3 ligases catalyze a thioester bond between a C-terminal glycine residue of ubiquitin and themselves and then transfer the ubiquitin to a substrate protein. HECT type E3 ligase family proteins possess a well-conserved, approximately 350 residue, catalytic HECT domain close to their C-terminal region [74, 75]. The HECT domain has a bi-lobal structure comprising an approximately 250 residue N-lobe, required for the binding to UBC-ubiquitin complex, and a C-lobe of around 100 residues, required for ubiquitin transfer [74, 76, 77]. Various linker sequences between the two HECT domain lobes mediate the properties of HECT type E3 ligases in accepting ubiquitin from E2 enzymes and transferring it to a target substrate.
The HECT type E3 ligase, E6-AP, can ubiquitinate p53 in the presence of human papillomavirus E6 protein [75, 78, 79], and another HECT E3 enzyme NEDD4 ubiquitinates SMAD proteins, thereby regulating transcription factors mediating TGFβ signaling [80], the P63 tumor antigen [81], and MDM2 [82]. HECW1 [83], HECW2 [84], WWP1 [85], HERC1 [86], HERC2 [87], and ITCH [88] also belong to the HECT type E3 ubiquitin ligase family.
RBR-type E3 ubiquitin transferases possess two RING finger domains, each of which is separated by an internal IBR (In Between RING) motif. These E3 ligases bind to the Cullin-RING ubiquitin Ligase (CRL) complex (see Cullin-type E3 NDD8 transferase), within which a neddylated cullin scaffold protein and a substrate recognition module are required for ubiquitin transfer. The first RING domain binds S-ubiquitinyl- [E2 UBC]-cysteine and transfers the ubiquitin to an internal Cys residue in the second RING domain (Reaction (6)), followed by transfer of the ubiquitin from the Cys residue in the second RING domain to a Lys in the acceptor protein (Reaction (7)). RBR-type ligases stimulate a cycling ubiquitination reaction via the S-ubiquitinyl-[E2 UBC]-cysteine in the first RING domain [88]. RBR-type ligase activity depends on the neddylation of the cullin protein in the CRL complex. RBR-type E3 ubiquitin ligases include Parkin, Parc, RNF19, RNF144, RNF216 RFA1 HOIP, and HHARI [89, 90].
RING E3 ubiquitin ligases (also referred to as RING E3 ligases or ubiquitin transferase RING E3 enzymes) transfer ubiquitin peptides directly from a ubiquitinyl-E2 UBC enzyme to an acceptor protein. The ε-amino group of a lysine residue of the target protein forms an isopeptide bond with the C-terminal glycine residue of ubiquitin (Reaction (9)). Unlike HECT E3 ligases, the RING-E3 domain does not create a catalytic thioester intermediate with ubiquitin through a Cys residue.
Human proteome analysis has identified approximately 580 genes encoding putative RING-type ubiquitin E3 ligase family proteins, which is more than the number of protein kinase genes (518) [91]. Among RING-type E3 ligase genes, 309 and 270 encode single and multi-subunit RING-type E3 ligase molecules, respectively. While RING-type E3 ubiquitin ligase family proteins do not form thioester intermediates with ubiquitin, they function as a scaffold for ubiquitin-charged UBC and the substrate. RING-type E3 ligases contain both a RING domain and a substrate-binding site, and almost half the RING proteins belong to multisubunit RING-type E3 ligases, which require an additional subunit for substrate recognition (see multisubunit RING-type ubiquitin ligases).
The RING domain was initially thought to function as a DNA binding domain because of the discovery of RING domain-containing proteins with DNA binding activity [92, 93]. RING-type E3 ligases were subsequently identified as interacting partners of the human E2 ubiquitin-conjugating enzyme UBCH5 [94], which has self-ubiquitination activity that depends on its RING domain sequence. The canonical RING domain structure consists of a Zn2+-coordination complex and o series of Cys and His residues and mediates E2-dependent ubiquitylation. The coordination complex with two zinc ions forms a cross-brace structure. RING finger domains have consensus sequences that are classified into two different types, C3HC4-type (RING-HC) and C3H2C3-type (RING-H2), according to the cysteine/histidine arrangement (where C = Cys and H = His) [95]. The C3HC5-type RING domain has different properties from the C3HC4 RING-HC finger [96], Casitas B-lineage Lymphoma (c-Cbl), which is a RING-HC type ligase. Ubiquitination activity modulates receptor tyrosine kinase signaling [97] and structural analysis of the c-Cbl-UbcH7-substrate tertiary complex showed that the interaction surface of the UbcH7 E2 enzyme is commonly used by both c-Cbl and HECT-type E3 ligases, where c-Cbl binds UbcH7 using both its RING domain and linker helix structure [50]. The amino acid residues involved in the interaction are structurally similar between E2 enzymes and E3 ligases.
BRCA1 forms a heterodimer with the RING-type ligase BARD. The dimerization of two RING-type E3 ligases results in upregulation of ubiquitination activity. By biochemical approaches, UbcH5c and UbcH7 enzymes were identified as candidate E2 enzymes for the BRCA1-BARD complex. Christensen et al. developed an excellent method for identifying E2-E3 pairing [98, 99], using a BRCA1-BARD fusion protein; BRCA1 can synthesize specific polyubiquitin chain linkages, depending on the presence of a paired E2 enzyme [98]. This approach has increased the identification of E2-E3 pairs; for example, RNF213, a RING-HC type E3 ligase and its paired UBC13E2 enzyme were identified using this method [100]. UBCH5b mutants, which can bind to E3 ligase, exhibit defective stimulation by E3 ligases [101]. Ubiquitin-charged E2 is conformationally activated by binding to the RING domain [101, 102, 103]. Furthermore, the interaction between E1 and E2 enzymes can direct substrate specificity, ubiquitin transfer, and polyubiquitin chain linkages.
Some RING-type ubiquitin ligase family members form hetero- or homo-multimers through the RING domain or its surrounding region. RING-RING complexes, including MDM2-HMDX, BRCA1-BARD1, and RING1-BMI1, form heterodimers. In heterodimers, one partner (HDMX, BRAD1, and BMI1) lacks ubiquitin ligase activity, while the other partner (MDM2, BRCA1, and RING1) has E2 UBC binding activity. Heterodimer formation leads to stabilization of E2-E3 binding, and in dimerizing E3 ligases, the five C-terminal residues of the RING domain are essential for both dimer formation and E3 activity [104, 105, 106].
TRAF2, cellular inhibitor of apoptosis (cIAP; officially known as BIRC2), SIAH, BIRC7, and RNF213 form homodimers [100, 107, 108, 109, 110, 111]. Dimeric BIRC7 recruits UBCH5B-ubiquitin and optimizes the donor ubiquitin configuration for transfer [112]. Homo- and hetero-dimerization of RING-type ubiquitin ligases may stabilize their interactions with ubiquitin-charged UBC E2 enzymes and optimize ubiquitin transfer activity.
Enzymes of the RING-type E3 ubiquitin ligase family do not bind directly to a substrate, but rather form a complex with a cullin scaffold protein and substrate recognition modules, referred to as CRL complexes. The SCF complex (SKP, Cullin, F-box containing complex) and anaphase-promoting complex/cyclosome (APC/C) (anaphase-promoting complex/cyclosome) are two major multisubunit RING containing complexes.
Ubiquitination by SCF and APC/C are implicated in the degradation of cell cycle proteins [113, 114, 115, 116]. APC/C regulates mitosis and entry into the G1 phase of the cell cycle, and SCF controls S phase progression.
SCF E3 complexes comprise at least four different subunits, including the F-box protein, SKP adaptor protein, Cullin scaffold protein, and Rbx RING-type E3 ligase [116, 117, 118, 119]. The F-box motif is a protein–protein interaction motif comprising approximately 50 amino acid residues. There is low sequence identity among F-box proteins, which recognize and bind substrate and bridge connections between adaptor proteins (including SKP1) and substrates. Phosphorylation of F-box proteins regulates their interactions with substrates. The SKP adaptor proteins, SKP2 (S-phase kinase-associated protein 2), β-TrCP (beta-transducin repeat-containing protein), FBW7, and FBXO4 are F-box proteins involved in cell-cycle regulation. Cullins are scaffold proteins for ubiquitin ligases; CUL1 is a subunit of the SCF complex, and the Cullin-homology domain at its C-terminus interacts with RING E3 ligases while the N-terminal region can interact with the adaptor protein, SKP2. Cullin family members function as adaptors for multisubunit RING-type E3 ligase complexes. The adaptor proteins SKP1 and CUL1 and the RING-type E3 ligase RBX1 form the CRL catalytic core complex.
APC/C is a multisubunit RING-type E3 ligase containing approximately 13 subunits. The Cullin subunit protein, APC2, and the RING H2 type E3 ligase, APC11, form the catalytic core domain [120, 121, 122]. TPR (tetratricopeptide residue) motif-containing subunits, including CDC16, CDC27, CDC23, and APC5, are thought to function as scaffold assembling proteins. Two co-activators, CDC20 (cell division cycle homologue 20) and FZR/CDH1 (Fzy-related/cell division cycle 20 related 1), bind to the CDC27 subunit of APC/C through their WD40 repeat and determine APC/C substrate specificity dependent on cell cycle to stages [115, 118, 123, 124, 125, 126, 127, 128]. The APC10 subunit contributes to optimal co-activator-dependent substrate recognition and substrate affinity [129, 130, 131]. APC/C-mediated ubiquitination depends on destruction box, KEN box, and CRY box sequences in the substrate [132, 133, 134, 135, 136, 137, 138, 139, 140]. Assembly of these co-activators into the APC/C complex in G1 or M phase during cell cycle is regulated by phosphorylation [141, 142, 143, 144].
The U-box domain displays a similar three-dimensional structure to the RING domain [145]. The U-box domain shows similarity to UFD2, which has a multiubiquitin chain elongation activity (known as E4 activity) [146]. Unlike the RING domain, the U-box domain does not form a coordination complex consisting of a central zinc ion through Cys residues; rather, the U-box domain structure is maintained by hydrogen bonding. The U-box domain has ubiquitin ligase activity, and the U-box protein, carboxyl terminus of HSC70-interacting protein (CHIP), also has E4 activity and includes tetratricopeptide repeat and U-box domains. The C-terminal U-box domain interacts with the molecular chaperones HSC70, HSP70, and HSP90 [147], in the presence of unfolded or misfolded proteins, where CHIP regulates protein quality control [148, 149].
U-box proteins have various structures; for example, ARC1, CMPG1, PUB13, and PUB20 contain armadillo which represents approximately 40 amino acids tandem repeats sequence. PUB23 has a serine/threonine kinase domain while PUB59 and PUB60 have WD40 repeats. These domains may coordinate the function of ubiquitin ligase activity by the U-box domain.
Research conducted over several decades has uncovered the cellular and biochemical functions involved in ubiquitin modification. Protein–protein networks and studies of complex structures have contributed to unraveling the biochemical mechanisms underlying ubiquitin modification. Identification of physiological E2 UBC-E3 ligase pairings has facilitated understanding of modification-types and associations. Deep understanding of the structures and biochemical processes involved in ubiquitin modification has contributed to determination of E3 ligase-substrate pairing and network construction. RING-type ubiquitin ligases comprise the largest gene family and are associated with various cellular processes and several diseases. Fundamental questions remain to be answered regarding the biological functions served by ubiquitin modification. Extensive further study of enzymes involved in ubiquitination and related processes has potential to contribute to the understanding of the pathogenesis of several diseases.
This work was supported by grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan to T. H.
The authors declare no conflict of interest.
The authors declare no competing interests.
IntechOpen - where academia and industry create content with global impact
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\\n\\nSara Uhac, COO
\\n\\nSara Uhac was appointed Managing Director of IntechOpen at the beginning of 2014. She directs and controls the company’s operations. Sara joined IntechOpen in 2010 as Head of Journal Publishing, a new strategically underdeveloped department at that time. After obtaining a Master's degree in Media Management, she completed her Ph.D. at the University of Lugano, Switzerland. She holds a BA in Financial Market Management from the Bocconi University in Milan, Italy, where she started her career in the American publishing house Condé Nast and further collaborated with the UK-based publishing company Time Out. Sara was awarded a professional degree in Publishing from Yale University (2012). She is a member of the professional branch association of "Publishers, Designers and Graphic Artists" at the Croatian Chamber of Commerce.
\\n\\nAdrian Assad De Marco
\\n\\nAdrian Assad De Marco joined the company as a Director in 2017. With his extensive experience in management, acquired while working for regional and global leaders, he took over direction and control of all the company's publishing processes. Adrian holds a degree in Economy and Management from the University of Zagreb, School of Economics, Croatia. A former sportsman, he continually strives to develop his skills through professional courses and specializations such as NLP (Neuro-linguistic programming).
\\n\\nDr Alex Lazinica
\\n\\nAlex Lazinica is co-founder and Board member of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his Ph.D. in Robotics at the Vienna University of Technology. There, he worked as a robotics researcher with the university's Intelligent Manufacturing Systems Group, as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and, most importantly, co-founded and built the International Journal of Advanced Robotic Systems, the world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career since it proved to be the pathway to the foundation of IntechOpen with its focus on addressing academic researchers’ needs. Alex personifies many of IntechOpen´s key values, including the commitment to developing mutual trust, openness, and a spirit of entrepreneurialism. Today, his focus is on defining the growth and development strategy for the company.
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\n\nCo-founded by Alex Lazinica and Vedran Kordic: “We are passionate about the advancement of science. As Ph.D. researchers in Vienna, we found it difficult to access the scholarly research we needed. We created IntechOpen with the specific aim of putting the academic needs of the global research community before the business interests of publishers. Our Team is now a global one and includes highly-renowned scientists and publishers, as well as experts in disseminating your research.”
\n\nBut, one thing we have in common is -- we are all scientists at heart!
\n\nSara Uhac, COO
\n\nSara Uhac was appointed Managing Director of IntechOpen at the beginning of 2014. She directs and controls the company’s operations. Sara joined IntechOpen in 2010 as Head of Journal Publishing, a new strategically underdeveloped department at that time. After obtaining a Master's degree in Media Management, she completed her Ph.D. at the University of Lugano, Switzerland. She holds a BA in Financial Market Management from the Bocconi University in Milan, Italy, where she started her career in the American publishing house Condé Nast and further collaborated with the UK-based publishing company Time Out. Sara was awarded a professional degree in Publishing from Yale University (2012). She is a member of the professional branch association of "Publishers, Designers and Graphic Artists" at the Croatian Chamber of Commerce.
\n\nAdrian Assad De Marco
\n\nAdrian Assad De Marco joined the company as a Director in 2017. With his extensive experience in management, acquired while working for regional and global leaders, he took over direction and control of all the company's publishing processes. Adrian holds a degree in Economy and Management from the University of Zagreb, School of Economics, Croatia. A former sportsman, he continually strives to develop his skills through professional courses and specializations such as NLP (Neuro-linguistic programming).
\n\nDr Alex Lazinica
\n\nAlex Lazinica is co-founder and Board member of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his Ph.D. in Robotics at the Vienna University of Technology. There, he worked as a robotics researcher with the university's Intelligent Manufacturing Systems Group, as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and, most importantly, co-founded and built the International Journal of Advanced Robotic Systems, the world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career since it proved to be the pathway to the foundation of IntechOpen with its focus on addressing academic researchers’ needs. Alex personifies many of IntechOpen´s key values, including the commitment to developing mutual trust, openness, and a spirit of entrepreneurialism. Today, his focus is on defining the growth and development strategy for the company.
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He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",institution:null},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v6KHoQAM/Profile_Picture_1584512086360",biography:"Sidra Mehtab has completed her BS with honors in Physics from Calcutta University, India in 2018. She has done MS in Data Science and Analytics from Maulana Abul Kalam Azad University of Technology (MAKAUT), Kolkata, India in 2020. Her research areas include Econometrics, Time Series Analysis, Machine Learning, Deep Learning, Artificial Intelligence, and Computer and Network Security with a particular focus on Cyber Security Analytics. Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:null},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:"Polytechnic University of Timişoara",institution:{name:"Polytechnic University of Timişoara",country:{name:"Romania"}}},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:null},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. She is a member of Indian Mathematical Society.",institutionString:null,institution:null},{id:"414880",title:"Dr.",name:"Maryam",middleName:null,surname:"Vatankhah",slug:"maryam-vatankhah",fullName:"Maryam Vatankhah",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Borough of Manhattan Community College",country:{name:"United States of America"}}},{id:"414879",title:"Prof.",name:"Mohammad-Reza",middleName:null,surname:"Akbarzadeh-Totonchi",slug:"mohammad-reza-akbarzadeh-totonchi",fullName:"Mohammad-Reza Akbarzadeh-Totonchi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ferdowsi University of Mashhad",country:{name:"Iran"}}},{id:"414878",title:"Prof.",name:"Reza",middleName:null,surname:"Fazel-Rezai",slug:"reza-fazel-rezai",fullName:"Reza Fazel-Rezai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"American Public University System",country:{name:"United States of America"}}},{id:"302698",title:"Dr.",name:"Yao",middleName:null,surname:"Shan",slug:"yao-shan",fullName:"Yao Shan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Dalian University of Technology",country:{name:"China"}}},{id:"125911",title:"Prof.",name:"Jia-Ching",middleName:null,surname:"Wang",slug:"jia-ching-wang",fullName:"Jia-Ching Wang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Central University",country:{name:"Taiwan"}}},{id:"357085",title:"Mr.",name:"P. Mohan",middleName:null,surname:"Anand",slug:"p.-mohan-anand",fullName:"P. Mohan Anand",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356696",title:"Ph.D. Student",name:"P.V.",middleName:null,surname:"Sai Charan",slug:"p.v.-sai-charan",fullName:"P.V. Sai Charan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"357086",title:"Prof.",name:"Sandeep K.",middleName:null,surname:"Shukla",slug:"sandeep-k.-shukla",fullName:"Sandeep K. Shukla",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356823",title:"MSc.",name:"Seonghee",middleName:null,surname:"Min",slug:"seonghee-min",fullName:"Seonghee Min",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Daegu University",country:{name:"Korea, South"}}},{id:"353307",title:"Prof.",name:"Yoosoo",middleName:null,surname:"Oh",slug:"yoosoo-oh",fullName:"Yoosoo Oh",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:"Yoosoo Oh received his Bachelor's degree in the Department of Electronics and Engineering from Kyungpook National University in 2002. He obtained his Master’s degree in the Department of Information and Communications from Gwangju Institute of Science and Technology (GIST) in 2003. In 2010, he received his Ph.D. degree in the School of Information and Mechatronics from GIST. In the meantime, he was an executed team leader at Culture Technology Institute, GIST, 2010-2012. In 2011, he worked at Lancaster University, the UK as a visiting scholar. In September 2012, he joined Daegu University, where he is currently an associate professor in the School of ICT Conver, Daegu University. Also, he served as the Board of Directors of KSIIS since 2019, and HCI Korea since 2016. From 2017~2019, he worked as a center director of the Mixed Reality Convergence Research Center at Daegu University. From 2015-2017, He worked as a director in the Enterprise Supporting Office of LINC Project Group, Daegu University. His research interests include Activity Fusion & Reasoning, Machine Learning, Context-aware Middleware, Human-Computer Interaction, etc.",institutionString:null,institution:{name:"Daegu Gyeongbuk Institute of Science and Technology",country:{name:"Korea, South"}}},{id:"262719",title:"Dr.",name:"Esma",middleName:null,surname:"Ergüner Özkoç",slug:"esma-erguner-ozkoc",fullName:"Esma Ergüner Özkoç",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Başkent University",country:{name:"Turkey"}}},{id:"346530",title:"Dr.",name:"Ibrahim",middleName:null,surname:"Kaya",slug:"ibrahim-kaya",fullName:"Ibrahim Kaya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"419199",title:"Dr.",name:"Qun",middleName:null,surname:"Yang",slug:"qun-yang",fullName:"Qun Yang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Auckland",country:{name:"New Zealand"}}},{id:"351158",title:"Prof.",name:"David W.",middleName:null,surname:"Anderson",slug:"david-w.-anderson",fullName:"David W. Anderson",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Calgary",country:{name:"Canada"}}}]}},subseries:{item:{id:"12",type:"subseries",title:"Human Physiology",keywords:"Anatomy, Cells, Organs, Systems, Homeostasis, Functions",scope:"Human physiology is the scientific exploration of the various functions (physical, biochemical, and mechanical properties) of humans, their organs, and their constituent cells. The endocrine and nervous systems play important roles in maintaining homeostasis in the human body. Integration, which is the biological basis of physiology, is achieved through communication between the many overlapping functions of the human body's systems, which takes place through electrical and chemical means. Much of the basis of our knowledge of human physiology has been provided by animal experiments. Because of the close relationship between structure and function, studies in human physiology and anatomy seek to understand the mechanisms that help the human body function. The series on human physiology deals with the various mechanisms of interaction between the various organs, nerves, and cells in the human body.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/12.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11408,editor:{id:"195829",title:"Prof.",name:"Kunihiro",middleName:null,surname:"Sakuma",slug:"kunihiro-sakuma",fullName:"Kunihiro Sakuma",profilePictureURL:"https://mts.intechopen.com/storage/users/195829/images/system/195829.jpg",biography:"Professor Kunihiro Sakuma, Ph.D., currently works in the Institute for Liberal Arts at the Tokyo Institute of Technology. He is a physiologist working in the field of skeletal muscle. He was awarded his sports science diploma in 1995 by the University of Tsukuba and began his scientific work at the Department of Physiology, Aichi Human Service Center, focusing on the molecular mechanism of congenital muscular dystrophy and normal muscle regeneration. His interest later turned to the molecular mechanism and attenuating strategy of sarcopenia (age-related muscle atrophy). 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