Preface

*Vector-Borne Diseases - Recent Developments in Epidemiology and Control reviews* many new developments in the study of diseases spread by arthropod vectors. Any group of writers that hopes to adequately address such a topic must represent a diverse group from a geographically dispersed area; the scientists and health workers who wrote this book are such a group. They address the impact of vectorborne diseases for humans and livestock in Africa, the effects of insecticide on entomological inoculation rates in Ethiopia, the effects of viral infection on the primary vector of Zika and dengue in South America, and the potential of certain chemical structures in the treatment of disease. The authors hail from Africa, India, North America and other places, so this book includes a variety of cultures and writing styles, just like the vulnerable populations that suffer from vectorborne infections. This broad presentation of expertise seems overwhelming, yet the continuously evolving disease threat can only be addressed with rapid development of technology and effective sharing of knowledge. The emergence and re-emergence of vector-borne diseases illustrates the need for such knowledge.

In recent years, Zika appears to have taken on a greater measure of pathology and then spread out of its usual confines in Africa to present a disease threat through much of the tropical and some of the temperate parts of the world. Previously thought to be a relatively mild, self-limiting illness, Zika is now known to have devastating effects on children. This example demonstrates the ever-changing threat due to vector-borne diseases, though it may seem like a distant threat to some observers. Such is not the case for other infections. In recent years, two tick-borne viruses capable of causing severe illness, even death, have emerged in the very central part of the United States. The emergence of these tick-borne viruses in the heart of a developed country demonstrates how little is really known about these disease agents. The reality is that there may be hundreds of vector-borne viral diseases still to be detected and described to the medical community.

This book is just a small attempt to share some of the important work going on in the study of vector-borne diseases. It represents a broad slice of research developments, some of which may contribute to new treatments or new methods of disease control. Perhaps ready access to information contained here will contribute to improved care or disease prevention for someone in the world. That is the hope of the authors of the chapters in this book.

#### **David Claborn, DrPH**

Master of Public Health Program, Missouri State University, Springfield, Missouri, USA

> **Sujit Bhattacharya** University of Calcutta, India

**Syamal Roy** National Institute of Pharmaceutical Education and Research, India

**1**

Section 1

Introduction to

Vector-Borne Disease Risk

Section 1


**5.2 The pros and cons**

The perceived potential benefits when applying SDM are multiple and include the improvement of patient's knowledge and self-esteem, even though not all of

#### *Shared Decision-Making towards a Higher Quality of Care: Is This the Norm? DOI: http://dx.doi.org/10.5772/intechopen.98752*

them are conclusively proven. It also improves patient's risk perception and reduces their anxiety. It is worth noting that the main drawbacks cited are usually based on clinicians' perceptions rather than an evidence base. Not all patients request it and not all consultations are suited to such approach as it takes more time and requires special training from the doctor's side [16].

A recent systematic review by [17] looked into the barriers and facilitators of SDM in clinical practice. It was found that the most commonly identified facilitators were positive impact on the clinical process, provider motivation, and positive impact on patient important outcomes. On the other side, common barriers were time constraints, lack of applicability due to the characteristics of the population, and the clinical situation.


**5. Ecological critique of modernity**

It now looks as if all the conditions are set for a proper redefinition of the modern paradigm. Modernity deconstructs itself both internally and externally, but the ecological critique also attacks dualism. Nevertheless, although it seems that all is in favor of this change, it seems analytically impossible from an environmental perspective. The ecological critique of modernity will allow us to measure the implications and contradictions involved in the attempts to step out of the modern framework. In relation it is important to consider that Latour situates his work in the horizon of political ecology to be built.

Why the ecological theory is incapable of rejecting the modern paradigm is quite simple. The ecological crisis consists in the degradation of the natural world. Now, as we see, the

8 Philippe Descola, "Constructing nature. Symbolic ecology and social practices", in *Nature and Society* : *Anthropological perspectives*, P. Descola and G. Palsson (ed), London : Routledge, 1996; p.94 9 Domestic animals seem to be the exception on this case. Generally, the owners develop a close relation

to their pets and thus develop a certain morality in regards to them, limiting their behaviour in regards to them (although many counter examples are available).

fundamental difference, both physical and spiritual, between a person and its counterpart, to establish analogical relations about the events affecting the two. Their mutual influence is only conceivable from the point of view of their difference. According to this, the way animals are treated always carries the risk to affect human condition and destiny. Animism functions in a totally different way. It involves a similarity on the spiritual level, but a difference on the physical level. This relation can emerge as a reciprocal relation, actualized as an exchange of services, souls, food or life energy. For example, in certain animist systems8, not only can humans feel indebted to non humans because of the taking of lives through hunting, but the hunters will admit that non humans take back from them by stealing body parts, food or vital energy. On the other hand, naturalism identifies nature as a completely separated world, heterogeneous to humanity. It does not identify any relations of reciprocity between the two worlds. In fact, although naturalism accepts a certain physical continuity between humans and non humans, it postulates a rupture on the spiritual level,

A first remark must be made: in these conditions, can an ecological project be suggested in regard to naturalism (as defined by Descola)? If any notion of communication between humans and non humans is absurd and if human interest is the only limit to a subjugation of nature, is a preservation or only a conservation of nature conceivable and practicable ? Environmental ethics are concerned by this possibility. They generally answer negatively. They affirm that the metaphysical dualism developed by modernity limits morality to cultural beings, namely humans. This prevents any kind of moral recognition to non

Looking at these different cosmologies enables us to see how naturalism is no more than a certain way of interpreting the world. It is a singular ontological formula, like the other ones (totemism, analogism, animism), that is organized from the practice schemes common to all cultures. Descola's work proves that no theoretical argument can justify the dominance of

It now looks as if all the conditions are set for a proper redefinition of the modern paradigm. Modernity deconstructs itself both internally and externally, but the ecological critique also attacks dualism. Nevertheless, although it seems that all is in favor of this change, it seems analytically impossible from an environmental perspective. The ecological critique of modernity will allow us to measure the implications and contradictions involved in the attempts to step out of the modern framework. In relation it is important to consider that

Why the ecological theory is incapable of rejecting the modern paradigm is quite simple. The ecological crisis consists in the degradation of the natural world. Now, as we see, the

8 Philippe Descola, "Constructing nature. Symbolic ecology and social practices", in *Nature and Society* : *Anthropological perspectives*, P. Descola and G. Palsson (ed), London : Routledge, 1996; p.94 9 Domestic animals seem to be the exception on this case. Generally, the owners develop a close relation to their pets and thus develop a certain morality in regards to them, limiting their behaviour in regards

Latour situates his work in the horizon of political ecology to be built.

which makes any notion of communication between them impossible to accept.

humans, but it is necessary to take care of them9.

the western conceptual framework.

**5. Ecological critique of modernity**

to them (although many counter examples are available).

definition of the crisis in itself is dependent on the dichotomy that is named as responsible for the crisis. Also to change the ontological paradigm would mean to cease the interpretation of environmental problems as dysfunctions affecting the natural world. Many problems are involved in this issue. As mentioned earlier, nature is the central theme to the environmental philosophies, their goal being to give nature moral value on account of an intrinsic value. Theoretically, it would be naive to give up the scheme that defines the object of their main research. Furthermore, the dichotomy is at the source of the creation of modern sciences, which reject any explanation of the phenomena in relation to final causes and defines space through geometry. Thus, to abandon the western cosmology is to abandon modern epistemology. But if the mechanist conception of nature has evolved, modern sciences not only possess extraordinary powers to explain phenomena, powers that are necessarily useful, but they are also the main if not the only tools we possess to come in contact with Nature, that is the biosphere. This is why it is so easy to build social controversies over global warming and the collapse of biodiversity for example. For non scientifically educated people, it is quite impossible to evaluate the extent of the damage of human activities on the ecosystems and the biosphere. It is then clear that the role of science must remain somewhat important unless we adopt, as certain branches of ecology do, a very different definition of the natural environment which is at stake. For André Gorz10, the naturalness of an environment refers to an organisation of the common world which functioning and structures can be intuitively and easily understood, without any kind of prerequisite learning. One can orient oneself and act relatively spontaneously in it. In this perspective, the ecological concern is a political one : it is about the colonization of the lifeworld by systems (technical-industrial-capitalist systems). But if the main issue is to care about biodiversity, and not only to resist to the expropriation of a common world that the systems destroy, we need to enter into scientific reasoning because we have to measure the impacts of our way of life on ecosystems. Common knowledge, intuitions and political concepts are not sufficient to build a representation of the anthropogenic damage caused on the ecosphere. In fact, scientists were the first ones to ring the bell after overseeing the extent of the degradation that was going on.

We are consequently facing a paradox. On one side, we are in front of a metaphysical paradigm that implies an unacceptable action in regard to our natural environment, but on the other, this paradigm is the only way leading to an understanding of this aberration. The paradigm is both problematic and helpful. Are we mistaken? Must we after all keep the modern metaphysic ? Or must we really abandon all references to modern nature? Is a practical knowledge of nature better suited to understand the problem? In brief, is it necessary to break down, in a radical way, modern naturalism and reject once and for all the categories of nature in opposition to society?

To understand this problem, we must understand the link between politics and ecology, for the problematic character of the nature-culture dichotomy is at the source of this environmental debate. To care about the *depletion of natural resources* involves being dependent on nature, not being outside of nature. Furthermore, the concept of a *responsibility* towards the planet supposes a relation of dependency of the planet in regard to human activity. Its state is modified by human activity and technical interventions necessary

10 André Gorz, *Écologie et politique*, Galilée, 1975.

The Nature-Society Controversy in France: Epistemological and Political Implications 49

does not promote any real "direct" experience of nature (the opening schedules of many installations restrict this in a formal way), nor does it allow any beneficial co-evolutive human practices (like transhumance in the Alps). The dichotomy still remains, the conditions of normativity have simply been reversed and we are in the presence of a natural

But also, if the environmental ethics' goal is to ultimately enact new policies capable of changing our relation to the environment, their efforts are concentrated on justifying moral interdictions and obligations in order to transform our ideological universe. Nevertheless, focusing on a moral dimension remains a vague enterprise. It does not imply to question the political and economic aspects of the situation that it questions. For this reason, we can fear that this project will remain inefficient because it fails to grasp the environmental crisis in its totality. Furthermore, it does not identify the social forces interested in considering nature as a pool of unlimited resources. Ignoring these considerations, environmental ethics must then rely on the only theoretical view left: an authoritarian imposition of new moral rules, only justified by philosophy, to modify our behaviour in regard to nature. An acceptation of

The perspective of political ecology is somewhat different, it is not concerned with a submission to the natural order. It can be seen as an extension of the Enlightenment as it promotes the construction of a society based on the moral rule of reason. It simply adds to the original political project of the Enlightenment new aspects of human activities. In this perspective, the logic of political ecology presents itself as pragmatic. It asserts the dominant economic paradigm, as noted by Catherine Larrère13, by confusing interests and values. In other words, it shares the same presuppositions concerning the economic paradigm. We can therefore doubt the capacity of political ecology to modify our society's inscription in

It is obviously clear that this project is in opposition with environmental ethics: nature is left aside to promote the cultural framework; we are in the presence of a subsumption of the natural order under the cultural order. As Descola remarks, a rational management of nature is at the end not profitable to its enactors as it leads, potentially, to the transformation of the world into a gigantic zoo; in this perspective, the survival of the blue whale or the preservation of Antarctica is carried out but only tributary to human conventions14. But is there not an essential difference, although difficult to grasp, between knowing oneself to be living in a managed, constructed environment and living in a world not conditioned by human activity? Does ecological concern lead to living in a zoo? What is at stake is the confrontation, more or less direct and more or less intense, with a human intention; and the possibility to avoid it. For the western world, this difference is essential because it relates to the concept of the Other, the Alterity, a concept which is described by Descola as a human constant. But unfortunately, political ecology has left aside the theoretical means to

13 Catherine Larrère, « L'Éthique environnementale : axiologie ou pragmatisme? », chapter 2, *Leçons de philosophie économique*, Tome II : Économie normative et philosophie morale, Paris : Alain Leroux et

14 Philippe Descola, "Constructing natures. Symbolic ecology and social practice", *art. cit*.,p.97

their point of view by the concerned citizens is not considered.

understand, or simply grasp, this Alterity.

subsumption.

nature.

Pierre Livet, 2005.

to the shaping of human societies. To summarize, we must admit that the understanding of the environmental crisis has challenged the theoretical apparatus of modernity because it involves new categories incompatible with the nature-society dichotomy.


**Acknowledgements**

I would like to deeply thank Dr. James M Tepper, Distinguished Professor of Rutgers University-Newark, and Dr. Satoshi Kida, Professor of the University of Tokyo, for reviewing the manuscript and offering many helpful comments and suggestions.


*Article* **Land Subsidence Susceptibility Mapping Using Persistent Scatterer SAR Interferometry Technique and Optimized Hybrid Machine Learning Algorithms**

**Babak Ranjgar 1, Seyed Vahid Razavi-Termeh 1, Fatemeh Foroughnia 2,\*, Abolghasem Sadeghi-Niaraki 1,3 and Daniele Perissin 4**

**Abstract:** In this paper, land subsidence susceptibility was assessed for Shahryar County in Iran using the adaptive neuro-fuzzy inference system (ANFIS) machine learning algorithm. Another aim of the present paper was to assess if ensembles of ANFIS with two meta-heuristic algorithms (imperialist competitive algorithm (ICA) and gray wolf optimization (GWO)) would yield a better prediction performance. A remote sensing synthetic aperture radar (SAR) dataset from 2019 to 2020 and the persistent-scatterer SAR interferometry (PS-InSAR) technique were used to obtain a land subsidence inventory of the study area and use it for training and testing models. Resulting PS points were divided into two parts of 70% and 30% for training and testing the models, respectively. For susceptibility analysis, eleven conditioning factors were taken into account: the altitude, slope, aspect, plan curvature, profile curvature, topographic wetness index (TWI), distance to stream, distance to road, stream density, groundwater drawdown, and land use/land cover (LULC). A frequency ratio (FR) was applied to assess the correlation of factors to subsidence occurrence. The prediction power of the models and their generated land subsidence susceptibility maps (LSSMs) were validated using the root mean square error (RMSE) value and area under curve of receiver operating characteristic (AUC-ROC) analysis. The ROC results showed that ANFIS-ICA had the best accuracy (0.932) among the models (ANFIS-GWO (0.926), ANFIS (0.908)). The results of this work showed that optimizing ANFIS with meta-heuristics considerably improves LSSM accuracy although ANFIS alone had an acceptable result.

**Keywords:** land subsidence; Geographic Information System (GIS); InSAR; machine learning algorithm; meta-heuristics; Iran


**4. Analysis of wavelet coefficient dependencies**

580 Advances in Wavelet Theory and Their Applications in Engineering, Physics and Technology

ratio (*SNR*) difference which is utilized to measure the performance gap of different

*SNR SNR R SNR R*

which is computed over a rate range for *N* rate points, where *SNR R*( ) denotes the

total distortion in the transform domain. The difference in *SNR* is computed relative to the uniform embedded quantizer (UEQ), i.e., *z* 1 . *SNR* for five embedded deadzone

We determined experimentally that at lower standard deviation ratios, *SNR* is positive

performs better compared to all other quantizers. Similarly, *z* 2 (i.e. the SAQ) performs the

results show that one cannot determine a single embedded quantizer that provides the best performance for *all* 3D meshes. However, an optimal quantizer per wavelet coordinate can

Given the fact that SAQ is closely linked to bit-plane coding and that it can be implemented using simple binary arithmetic, one concludes that SAQ is not an optimal, but an acceptable

 2 1

2 1 120 . For

quantizers is plotted in Fig. 7. over a wide range of standard deviation ratios

general, small standard deviation ratios correspond to

Fig. 7. *SNR* difference for five EDSQs with respect to UEQ.

solution in scalable coding of meshes.

normal meshes, while higher ratios correspond to

be determined based on the corresponding

2

1 1

extracted from the model.

2 1 120 , SAQ is not always the optimum, but lies not far

2 1 290 600 , while *z* 2.5 performs the best for 600

2 1 120 , the difference between SAQ and the UEQ is significant, and hence

10 *SNR* 10log ( ) *D* is computed in dBs, where *D* is the

0.9 is considered, as mentioned in Section 3.2.

2 1 120 290 , the quantizer with *z* 1.5

1 , observed in normal meshes. These

 2 1

close to 1 , observed in non-

 2 1 . In

. In Fig.

1 () ()

*z z*

*N* ,

embedded quantizers is defined as:

discrete *SNR*-rate function. The

7., the commonly observed proportion

and the UEQ is optimal for

from the optimum.

UEQ is the optimal choice. For

Overall, for

best in the range

Similar to images, parent-children and neighboring wavelet coefficient dependencies exist in wavelet decomposed mesh structure. In Fig. 8 (middle, right), the positions of the wavelet coefficients at different levels of the transform are shown with the help of white and dark circles. In particular, wavelet coefficients have a one-to-one correspondence with the edges of the coarser mesh. For each wavelet coefficient there are rings of neighboring coefficients which lie in the same wavelet subband – see Fig. 8 (right). Also, a set of four wavelet coefficients have a parent coefficient at the next coarser resolution – see Fig. 8 (middle, right).

Fig. 8. Parent-children and neighboring wavelet coefficients: actual mesh (left); coarser meshes after one (middle), and after two wavelet decomposition levels (right).

Statistical intraband dependencies exist between neighboring coefficients of each resolution level. The main reason for the existence of these dependencies is the smoothness of the surface. Wavelet coding paradigms that exploit the intraband dependencies between the wavelet coefficients are known as intraband wavelet codecs such as block-based coding techniques (Munteanu et al., 1999a), quadtree coding approaches (Munteanu et al., 1999b), and the EBCOT codec employed in the JPEG-2000 scalable image coding standard (Taubman, 2000).

Statistical dependencies also exist between the parent and descendants (children) due to the natural decay of the coefficients' magnitude for increasing frequencies. In other words, if a parent coefficient magnitude is below a certain threshold, then there is a high probability that the magnitude of its descendants will be also below this threshold. This corresponds to the so-called zerotree-model, firstly introduced by Shapiro in (Shapiro, 1993). The wavelet coding paradigms that exploit the parent-children dependencies are known as interband wavelet codecs.

Finally, there is a third category of coding paradigms, exploiting both the interband and intraband statistical dependencies between the wavelet coefficients. They are generally known as composite codecs, EZBC (Hsiang & Woods, 2000) and the ECECOW approach of (Wu, 1997) are typical examples of codecs in this category.

In the following, an information theoretical analysis of the aforementioned coefficient dependencies is presented. Our aim is to single out the type of dependencies which can ensure best compression performance in the context of wavelet-based mesh compression.

#### **4.1 Mutual information analysis**

The mutual information is the reduction in the entropy of one random variable due to the knowledge of the other random variable.

$$I(X;Y) = h(X) - h(X/Y) \ , \tag{22}$$

Optimized Scalable Wavelet-Based Codec Designs for Semi-Regular 3D Meshes 583

hand, ensures that there are always sufficient numbers of observations in each bin, and

Mesh Type MESH INTRABAND INTERBAND COMPOSITE INTRABAND INTERBAND COMPOSITE

Table 3. Average mutual information in bits for several non-normal and normal meshes.

Table 3 shows the average mutual information results for interband, intraband and composite dependencies for various mesh models. Since in mesh coding three different components need to be coded for each vertex position in space, the average mutual information ( )/3 *avg X Y Z I III* is reported instead of the mutual information for the three components individually. It is observed from Table 3 that for both normal and non-normal meshes mutual information of interband models is the least, independent of the wavelet transform employed. On the other hand mutual information for intraband models is significantly higher than for the interband models. Finally, composite models which gather the characteristics of both interband and intraband models exhibit even higher mutual information than interband or intraband models alone. Mathematically we can summarize

Experimental results for the mutual information based estimation of interband, intraband and composite dependencies seem to indicate that exploiting the composite dependencies should be preferred. Additionally, it is important to point out that favoring intraband over zerotree-based interband models brings along the additional benefit of resolution scalability. Specifically, by following an intraband codec design, only those wavelet subbands that are needed in order to reconstruct a target mesh resolution-level need to be encoded, while the others can be discarded. This does not hold in case of interband and composite codec designs, due to the tree-structures that span all the wavelet decomposition levels. Since composite models cannot be discarded altogether due to their highest mutual information property, a careful implementation of a composite mesh coding system needs to be carried out into order to get the benefit of both the higher compression efficiency and the resolution

Finally, it is important to point out that the differences in terms of mutual information do not give any indication about the final performance differences between interband, intraband and composite coding systems. Hence, an actual development and comparison of such coding systems is needed in order to experimentally validate the conclusions of this

**Butterfly Loop**

*IXP IX IXP* ; ; ;; *X* **n n** *X XX* .

**Non-Normal**

**Normal**

our numerical findings as:

scalable decoding at the same time.

It is known that *IXY IYX* (,) (, ) . In the wavelet domain, we define the following mutual information quantities:

(; ) *X IXP* : denotes the mutual information between a wavelet coefficient *X* and its parent coefficient *PX* .

(; ) **n***X I X* : denotes the mutual information between a wavelet coefficient *X* and its neighboring wavelet coefficients 1, 2, , **n** [ , ,.... ] *X X X NX nn n* .

*IXP* (; ; ) *X X* **n** : denotes the composite mutual information.

From the basics of information theory (Cover & Thomas, 1991), we know that:

$$I(X; P\_X; \mathbf{n}\_X) \ge I(X; \mathbf{n}\_X) \quad \text{and} \quad I(X; P\_X; \mathbf{n}\_X) \ge I(X; P\_X). \tag{23}$$

For the estimation of (; ) **n***X I X* , we need to estimate the joint PDF (, ) *x p x n* which can have high dimensionality depending on the number of considered neighbors. Since the amount of data needed to accurately estimate a PDF increases exponentially with its dimensionality, it is difficult to reliably estimate a high-dimensional PDF. To alleviate this problem, the reduction in dimensionality as proposed in (Liu & Moulin, 2000) is used here. We summarize the neighborhood of *X* through a so-called summarizing function *T g* ( ) **n***X* . This function maps the neighboring wavelet coefficients to a single value. We note that such a many-to-one summarizing function cannot increase the mutual information, i.e.,

$$I(X; \mathbf{n}\_X) \ge I(X; T) \,. \tag{24}$$

Equality in the above equation holds if **n***X T X* forms a Markov chain. The summarizing function used in our analysis is:

$$T = f(\mathbf{n}\_X) = \sum\_{i=1}^{N} \left(n\_{i,X}\right)^2. \tag{25}$$

Due to this summarizing function, it is sufficient to compute the joint PDF *p*(,) *x t* , *t* is a realization of the random variable *T* , instead of (, ) *x p x n* , for the estimation of the intraband mutual information (; ) **n***X I X* .

In our analysis, the mutual information for the defined quantities is estimated using the adaptive partitioning method (Darbellay & Vajda, 1999) instead of the traditional histogram method. This is because the histogram method highly depends on the bin size and for a small bin size there may not be sufficient number of observations in some bins to make a correct estimate. The adaptive partitioning method (Darbellay & Vajda, 1999) on the other

The mutual information is the reduction in the entropy of one random variable due to the

It is known that *IXY IYX* (,) (, ) . In the wavelet domain, we define the following mutual

(; ) *X IXP* : denotes the mutual information between a wavelet coefficient *X* and its parent

(; ) **n***X I X* : denotes the mutual information between a wavelet coefficient *X* and its

For the estimation of (; ) **n***X I X* , we need to estimate the joint PDF (, ) *x p x n* which can have high dimensionality depending on the number of considered neighbors. Since the amount of data needed to accurately estimate a PDF increases exponentially with its dimensionality, it is difficult to reliably estimate a high-dimensional PDF. To alleviate this problem, the reduction in dimensionality as proposed in (Liu & Moulin, 2000) is used here. We summarize the neighborhood of *X* through a so-called summarizing function *T g* ( ) **n***X* . This function maps the neighboring wavelet coefficients to a single value. We note that such

Equality in the above equation holds if **n***X T X* forms a Markov chain. The

Due to this summarizing function, it is sufficient to compute the joint PDF *p*(,) *x t* , *t* is a realization of the random variable *T* , instead of (, ) *x p x n* , for the estimation of the intraband

In our analysis, the mutual information for the defined quantities is estimated using the adaptive partitioning method (Darbellay & Vajda, 1999) instead of the traditional histogram method. This is because the histogram method highly depends on the bin size and for a small bin size there may not be sufficient number of observations in some bins to make a correct estimate. The adaptive partitioning method (Darbellay & Vajda, 1999) on the other

 **n** 2

, 1 () . *N X iX i Tf n*

( ; ; ) ( ; ) ( ; ; ) ( ; ). *XX X* **nn n** and *XX X IXP IX IXP IXP* (23)

(; ) (;) *X IX IXT* **n** . (24)

(25)

From the basics of information theory (Cover & Thomas, 1991), we know that:

a many-to-one summarizing function cannot increase the mutual information, i.e.,

*IXY hX hX Y* (;) () ( /) , (22)

**4.1 Mutual information analysis**

information quantities:

coefficient *PX* .

knowledge of the other random variable.

neighboring wavelet coefficients 1, 2, , **n** [ , ,.... ] *X X X NX nn n* . *IXP* (; ; ) *X X* **n** : denotes the composite mutual information.

summarizing function used in our analysis is:

mutual information (; ) **n***X I X* .

hand, ensures that there are always sufficient numbers of observations in each bin, and provides reliable estimates of the mutual information.

Table 3. Average mutual information in bits for several non-normal and normal meshes.

Table 3 shows the average mutual information results for interband, intraband and composite dependencies for various mesh models. Since in mesh coding three different components need to be coded for each vertex position in space, the average mutual information ( )/3 *avg X Y Z I III* is reported instead of the mutual information for the three components individually. It is observed from Table 3 that for both normal and non-normal meshes mutual information of interband models is the least, independent of the wavelet transform employed. On the other hand mutual information for intraband models is significantly higher than for the interband models. Finally, composite models which gather the characteristics of both interband and intraband models exhibit even higher mutual information than interband or intraband models alone. Mathematically we can summarize our numerical findings as:

$$I(X; P\_X) \ll I(X; \mathbf{n}\_X) \ll I(X; P\_X; \mathbf{n}\_X) \cdot \tag{26}$$

Experimental results for the mutual information based estimation of interband, intraband and composite dependencies seem to indicate that exploiting the composite dependencies should be preferred. Additionally, it is important to point out that favoring intraband over zerotree-based interband models brings along the additional benefit of resolution scalability. Specifically, by following an intraband codec design, only those wavelet subbands that are needed in order to reconstruct a target mesh resolution-level need to be encoded, while the others can be discarded. This does not hold in case of interband and composite codec designs, due to the tree-structures that span all the wavelet decomposition levels. Since composite models cannot be discarded altogether due to their highest mutual information property, a careful implementation of a composite mesh coding system needs to be carried out into order to get the benefit of both the higher compression efficiency and the resolution scalable decoding at the same time.

Finally, it is important to point out that the differences in terms of mutual information do not give any indication about the final performance differences between interband, intraband and composite coding systems. Hence, an actual development and comparison of such coding systems is needed in order to experimentally validate the conclusions of this

Optimized Scalable Wavelet-Based Codec Designs for Semi-Regular 3D Meshes 585

Using the octree-based bitplane coding, separate symbol streams are first generated for all bitplanes of each resolution subband. Depending on the type of scalability, i.e., resolution or quality scalability, the encoded symbol streams are entropy coded using a predefined progression order of bitplanes. For quality scalability, bitplanes of certain significance, from all resolution subbands, are first encoded before encoding the bitplanes of lower significance. However, in resolution scalability mode, all bitplanes of a lower resolution subband are progressively encoded before encoding the next higher resolution

We compared the SIM codec with the PGC codec for both normal and non-normal 3D meshes. The decoded meshes are compared against the original semi-regular input meshes using the peak signal-to-noise ratio (PSNR) as the distortion metric, which is defined

where *peak* and *RMS* denote the size of the bounding box and the root mean squared error calculated on the distances between the decoded vertex positions with respect to the original

Fig. 9 depicts PSNR versus bitrate (bits per semi-regular vertex) plots, evaluated for the semiregular non-normal Venus and Bunny meshes using the Butterly transform. The results demonstrate that for both meshes, SIM yields superior performance when compared to PGC.

(a) (b) Fig. 9. PSNR versus bitrate for non-normal mesh models in the quality scalability mode: (a) Venus, (b) Bunny . The lifted Butterly transform is employed for all three codecs.

40

60

80

*PSNR* (*dBs*) 100

120

140

3xC SIM PGC

The averaged gain in PSNR when compressing the Venus and Bunny meshes goes up to 2.22 dB and 2.35 dB, respectively. One may also notice the increasing performance difference with increasing bitrates; this indicates that the SIM coder tends to code the high frequency information more efficiently. For the spatially adaptive wavelet transform (SAWT) the

compression results are reported in (Denis et al., 2010a).

0 5 10 15 20 25 30 40

*Bitrate* (*bpv*)

*peak PSNR*

dBs 10 20 log

*RMS* ,

0 5 10 15 20 25 30 35 20

*Bitrate* (*bpv*)

subband.

ones, respectively.

3xC SIM PGC

*PSNR* (*dBs*)

as:

information-theoretic analysis of wavelet-based mesh coding designs, which is presented next.


*1.3.3 Pulsed Laser Deposition*

Thermal evaporation and Magnetron sputtering units having few limitations merely two to three composite materials deposited at prompt time. To overwhelmed constraint Laser ablation or PLD (schematic of PLD is shown in **Figure 10a**) had better established to be an unique furthermost suitable techniques for the deposition of thin films comprising an unpredictable through composite stoichiometry. Also PLD has some inimitable advantages such that in-situ temperature controller, partial pressure atmospheric condition, layer by layer coatings, varying the ablation rate exclusively to develop micro/ Nano structured thin film, even this system delivers sufficient microstructure variation and morphologies necessitate for superior electrochemical performance as the most important benefits in PLD are larger deposition rate, precise thickness control unit, capability to functioning in high reactive background gases pressures, and fewer nonconformity from the target composites [50]. The thin film fabrication process parameters of the PLD is exposed in **Table 2**. In this technique Krypton Fluorine (KrF) premixed laser source was used to ablate

#### **Figure 10.**

*(a) Schematic diagram of PLD coating unit; (b) photographical image representation for "laser plume" at CSIR-CECRI India (Reprinted with permission from Ref. [28]. Copyright 2020 Royal Society of Chemistry).*

#### **Table 2.**

*Thin film fabrication process parameters in pulsed laser deposition (PLD).*

target of the materials in a high vacuum pressure up to 10−7 mbar with the help of turbo molecular pump. The laser excimer emits the laser pulse energy 0.8 joule/ pulse at a wavelength 248 nm uses high power (40 W) laser pulses to melt, and evaporate and ionize material from the surface of a target. This laser ablation event produces a high plasma plume that magnify intensely ahead of the target surface, and the produced laser plume is shown in **Figure 10b**. Additionally, PLD unit having rotating target carousel is used to make larger composite materials film in an ambient vacuum condition. PLD is used to fabricate all metals (Au, Pt, Ni, Ag, Cu, Al, etc.), metal oxides (MnO2, V2O5, Co3O4, NiO, SnO2 etc.), metal sulfides (MoS2, CoS, NiS, FeS and VS2 etc.), metal nitrides (CrN, TiN, VN and BN), conducting polymers (PANI, PPy etc.), solid state polymers (LIPON etc.) and other metalloid compound thin films for countless applications. While PLD is the stoichiometric conversion of the ablated material on or after the target directed to the substrates and the crystallite phase of the subsequent film is not essentially the similar that the target of materials.

From these consequences PLD is one of the ideal candidates to form micro / Nano structured films for energy storage and energy saving applications. Recently, de Krol et al. fabricated BiVO4 thin film prepared by PLD for solar water splitting application [51]. Wang et al. investigated supercapacitor performances of NiSe thin film electrodes fabricated by PLD technique and the corresponding electrodes delivered specific capacitance value 696 F g−1 [52]. Patil et.al studied effect of temperature of CoFe2O4 thin film prepared via PLD for supercapacitor studies [53]. This work CoFe2O thin film annealed at 450°C electrode exhibited 777 F g−1. Julien et al. examined Li2TiO3 thin film electrodes produced by PLD aimed at energy storage application. Here the LTO thin film grown at 600°C delivered a specific discharge capacity of 46 μAh cm−2 [54]. Lastly Author group demonstrated WO3 and V2O5 symmetric thin film supercapacitors and Supercapbattery device assembled by using in-situ annealed thin film electrodes prepared by PLD. Thin flexible Supercapbattery device presented superior charge storage performance, also the device displayed high volumetric capacitance about 40 F cm−3 [28]. As a final point, PLD is the most appropriate technique for energy storage device fabrication.

#### **1.4 Current electrode materials for thin film energy storage**

Current commercial flexible energy storage system contains anode and cathode are regularly exclusive based on the intercalation/ deintercalation principal of potassium or lithium ions. Even though these flexible energy storage system by now exhibit a greatly upgraded when compared to the conventional supercapacitors of 10 years ago, their energy storage mechanism principle is also subject to essential limitations

#### *Physicochemical Approaches for Thin Film Energy Storage Devices through PVD Techniques DOI: http://dx.doi.org/10.5772/intechopen.99473*

prominent to comparably low energy storage system densities. One of the challenging application for supercapbatteries in terms of specific energy and power densities in future portable Micro-electronics. Transition metal oxides such as RuO2, Fe2O3, Co3O4, WO3, V2O5, NiO, Bi2O3 etc., and ternary metal oxides NiCo2O4, ZnCo2O4, NiMoO4, ZnWO4 etc., have long been disregarded as possible electrode materials for all kinds of energy storage system such as Lithium ion batteries, Supercapacitors and Supercapbatteries because of the they having high pore volume with high crystalline nature for insertion / deinsertion of electrolytic ions. The positive electrode as the cathode, the positive electrode frequently has a superior potential than the negative electrode (Anode). The current always streams from the positive electrode to the negative electrode via the peripheral circuit, and the electrons movement in the opposite way. However, cathode (positive) and anode (negative) are well-defined, by the electrochemical electrode reaction being reduction or oxidation.

#### *1.4.1 Anodic materials*

For fabrication of hybrid energy storages such as ASCs and Supercapbatteries, anodic materials are promising candidate to meet future energy demands. Usually anodic materials charges stored through an electrolytic ions intercalation/ deintercalation mechanism. As a result, the rate capability performance of hybrid EES is restricted by the sluggish kinetics of ion diffusion in the solid surface, as the surface adsorption–desorption approaches at the cathodic materials are noticeably more rapidly than the Faradaic reactions occurs at the anode, More than a few materials, Bi2O3, MoO3, Fe2O3, VN and WO3 are being investigated as the suitable anodes to fabricate hybrid EES because they are having high theoretical specific capacity, faster ions diffusion and easily allowing to intercalation of electrolytic ions.


Yet, the pessimistic observation that initiated my change of perspective on the role of digital media in accessing text can be reconsidered in the light of this small journey through various assessments. Not all is good in digital technologies, and their being embedded in the socio-economic fabric of highly resourced capitalism does not facilitate unselfish practices. But there is little doubt that sharing and steering towards sustainable infrastructures — solutions that have proved e˙ective in modern contexts — can contribute to alleviating the environmental cost of producing, distributing, enjoying, and preserving access to text.

### Conclusion

While I have spent most of my adult life archiving, publishing, writing, and editing, convinced that advances in knowledge are facilitated by digital media, the accelerating climate crisis has moved the parameters of what I have always considered my vocation in a way that is fundamental for the values that are at the heart of my vision of textual studies. The extent to which my inner orientation was shaken by this shift in the way I conceived my mission as a scholar called for a new form of enquiry. For once, I did not publish a blog post, a scholarly article, a series of tweets, or an edition of an old manuscript — in the hope, maybe, of reaching new readers and opening new transmission chains, but also, certainly, to find peace and reconcile with the scholarly choices I had made across the years. There is something contradictory in writing a book about the fact that so much is changing about texts and books that I do not really know how long the book will be there for an audience to read, in what form, or for whom. But it mattered to me to shed light on the consistency between considerations on environmental issues and reflexive work on digital media. In this book, I wanted to show that philology, Open Access, and environmental evolutions are intimately intertwined.

This called for detours. I revisited many of my earlier publications in a condensed form in the first chapters of this book. The European perspective I bring to such topics as archiving, text constitution, or the advent of a publisher-based book market is strongly connected to the objects I know best: early modern manuscripts, scholarly books, and artefacts encapsulating the canons of literary history. Considering them in their digital dimension opened new perspectives on the theories and artefacts of my early career, even more so in the environmental context of more recent years. With my education and my training, I am not able to o˙er more than what I think remains a traditional European perspective. I am also aware that I have only superficially touched on economic and legal aspects that would add a decisive dimension to the argument, just as my scattered educational suggestions lack a theoretical basis. But for all that is not in this book, I still hope that what there is can open a much

needed dialogue, and bring to the question of access to text in the context of the climate crisis the attention it deserves.

Considering the opposition between nature and culture has long been a theoretical, if not rhetorical, topic of interest in north-western countries. Technological advances have now become so dominant in the regulation of interpersonal relationships that natural physical time and space tend to lose their mental substance as a framework of reference. Drawing a direct line between elaborate technological artefacts such as digital editions and the natural resources they require in order to be manufactured is not instinctive, nor is it culturally fostered in north-western countries. It was my goal here to uncover all the intermediary steps that digital philology can provide in order to make this process visible and to raise awareness of the emergency there is to show it more clearly. By creating cultural artefacts, we destroy natural resources: this finding is so crushing that it can lead to the conclusion that cultural activities, at large, are destructive — a similar predicament to that of activists spattering soup on Van Gogh's *Sunflowers*. But, like them, I do not want to break the glass protection that preserves the artwork.

With this book, I wanted to show that as a society, even as a global one, we have been able to build the material and intellectual conditions to provide access to community-building cultural artefacts, especially text. It is up to today's actors to turn it into an asset in the context of the climate crisis and to envision a future where access to text is a common good that even more societies can rely on than it is the case today. We know how to make access to text sustainable in the middle and long run with hybrid settings building on physical artefacts and the digital forms of their representation. We know that in order to make it work, we need to o˙er dedicated training and erect infrastructures to preserve and distribute information that will be accessible to all. And we know there is no time to lose.

Having reached the end of this journey through text, yet another question is still waiting for an answer. What should I do with the old papers I found in the family home? My mother would throw them away, my daughter would want to keep all of them, but she does not know how to do so. It is pretty much up to me to decide, and to choose what remains in the drawer, what goes online, and what will only be a vague

memory in the stories I tell my children and hope that they pass them on to the next generation.

Elizabeth Rankin and James Hobson performed the copy-editing and proofreading.

Jeevanjot Kaur Nagpal designed the cover. The cover was produced in InDesign using the Fontin font.

Gilles Blanchard typeset the book in LaTeX, and Anne Baillot indexed the manuscript.

Cameron Craig produced the paperback and hardback editions.

This book has been anonymously peer-reviewed by experts in their field. We thank them for their invaluable help.


2.2.4. Minerals, Vitamins, Urea, Enzymes, Hormones, and Other Ingredients

Mineral substances in milk contain from 0.6 to 0.8%. The main macronutrients include: calcium, magnesium, potassium, sodium; microelements: copper, iron, zinc, cobalt, manganese, iodine, etc. Milk contains almost all vital vitamins. They are represented by fat-soluble (A, D, E, K) and water-soluble (B1, B2, B3, PP, B6, B9, B12, C, H) vitamins. Another important component of milk is urea. Monitoring the level of urea in milk and blood allows to adjust the feeding diet in a timely manner, as well as improve the quality of milk and dairy products. Urea is also added to improve the thermal stability of milk and to increase the total nitrogen content (milk protein), which is a type of adulteration. Milk also contains more than 20 native enzymes, hormones (prolactin, oxytocin, somatotropin, thyroxin), pigments (carotenoids that determine the color of milk), gases such as nitrogen, oxygen, carbon dioxide, ammonia (they get into milk from blood, air during milking, pipeline transport), etc.

Thus, the composition of milk is complex and unstable, and the absence of one of the substances or a deviation of its quantity from the norm usually indicates a sick state of the animal, an inadequacy of the diet (feed) or falsification of milk.


**2. Theoretical framework and methodology**

The research relies on a person-organization fit (P-O fit) theory. It suggests that employees' decision to remain depends on congruence of their values with corporate values, personality congruence with an imaginary ideal employee in terms of attitude, and work environment congruence, when individual characteristics satisfy employees' expectations [13]. Both employers and employees themselves expect deviation of mothers' behaviors from accepted standards, which might negatively affect their relationship with team members, affecting person-organization fit,

#### *Inclusion of Home-Centred Women DOI: http://dx.doi.org/10.5772/intechopen.98943*

perceived stress, self-efficacy, and career decision-making [14]. To attract and retain women with childcare commitments organizations should offer specific opportunities, encouragement and inclusiveness [15].

In combining groups of expectations of employer and employee, we rely on contextual Strategic HRM Framework [16]. It assumes that employers' initiatives related to employees should satisfy four levels of fit: institutional, organizational, strategic and internal level of fit, not contradicting existing SHRM system. Lepak and Snell [17] systematized key attributes of established Work Systems; Bazigos et al. [18] summarized options for strategic fit; Thomas and Ely [19] – options for organizational fit. Institutional fit was a black spot for several decades, however, articles published after 2010th covered this gap by contrasting western neoliberal context to liberal (e.g. [20]) and to contexts of the "rest" countries (e.g. [21]).

However, the framework is lacking the fifth important level – individual fit, which became important with the dominance of Harvard model for SHRM [22]. To cover the missing part we focused on the identity salience [23]: which efforts employees with childcare commitments should bring to readjust their self-understanding and reach higher self-esteem despite "identity gaps" - perceived identity threats caused by incongruence between the self and the socio-structural context [24]. Such internal process of self-construction is called an identity work [6]: in this case meaning intersection of work and childcare commitments.

The research question is what affects women with childcare commitments in their decision to return to the same employer after the maternity leave. Previously similar question raised Hakim, introducing influential preference theory [25], about women choice between productive and reproductive work. According to it, there are three types of working women: home-centred, work-centred and adaptive workers, who balance between work and home.

**Tables 1** and **2** summarized findings of the comprehensive literature review of articles published between January 2017 and April 2019 by the journals listed

#### **Table 1.**

*Summary of the contextual fit requirements for legitimacy of initiatives suitable for home-centred women.*

#### **Table 2.**

*Set of initiatives suitable for home-centred women.*

in the Academic Journal Guide 2018 of the Chartered Association of Business Schools specialized in gender research and management. The sample was enriched by manual search in the database Scopus, using key words "inclusion", "childcare", "motherhood", "fatherhood", "parenting". We omitted interruptions, which were beyond organizational control, focusing only on managerial practices related to individual abilities (A) and motivation (M), as well as opportunities (O) for employees. AMO is a widely used framework for analysis of SHRM systems [27].

Empirical part refers to data collected within the period September 2018 — October 2019. The questionnaire was spread online through social networks of Selfmama audience. Selfmama is an educational project for urban women with childcare commitments. It aims to help those who are in search of balance, new development prospects, useful knowledge and networking, as well as those in need of inspiration and support. It organizes learning events both offline and online, like conferences, internships, webinars, master-classes, etc.

The questionnaire was filled in by 950 respondents, however, after the preliminary data cleaning, 721 responses were taken into consideration. All participants are women with children, who live in a large Russian city with over 1 mln. population. All of them experienced maternity leave and had work experience prior to or during the leave. Their age is between 25 and 45 years old. Omitted observations did not correspond to any of the mentioned criteria. We split all sample into four

*Inclusion of Home-Centred Women DOI: http://dx.doi.org/10.5772/intechopen.98943*

cluster, according to signals related to particular frame of reference. Women, who did not work despite the end of maternity leave, formed the first cluster. The fourth cluster formed respondents who shared desire to become entrepreneur, being selfemployed or work as free-lancer, and those who actually selected these roles before the maternity leave or after. The third cluster formed directors, senior managers, rare specialists, who did not think about being entrepreneur, self-employed or try themselves in free-lance work. The rest employees formed the second cluster.


**3.1 Origin of flaky tail mice**

6 Atopic Dermatitis – Disease Etiology and Clinical Management

pyrrolidone-5-carboxylic acid (PCA). The concentrations of UCA and PCA in SC in the carriers of *FLG* mutations were significantly lower than those in healthy donors (Kezic, et al., 2009).

An *in vitro* experiment using filaggrin knocked down human organotypic skin cultures showed enhanced penetration of hydrophilic dye Lucifer yellow, smaller lamellar bodies, and deficiency of their typical lamellae without altered lipid composition (Mildner, et al., 2010). In addition, UCA, one of the filaggrin-derived free amino acids and as an important UV absorbent within SC, was decreased following filaggrin knocked down, leading to increased

The SC serves as a biosensor of the external environment and a link between innate and adaptive immune systems (Vroling, et al., 2008). The critical association between the abnormal barrier in AD and Th2 polarization may in part be explained by the production of the cytokine, thymic stromal lymphopoietin (TSLP) (Ebner, et al., 2007). TSLP is expressed by epithelial cells, with the highest levels seen in lung-derived and skin-derived epithelial cells (Soumelis, et al., 2002, Ziegler, 2010), and is highly detected in the lesional skin of AD (Soumelis, et al., 2002) Inducible TSLP transgene specifically in the skin leads to the development of a spontaneous Th2-type skin inflammatory disease with the hallmark

TSLP has been shown to activate dendritic cells to drive Th2 polarization, through upregulation of the co-stimulatory molecules CD40, CD80, and OX40L, triggering the differentiation of allergen-specific naïve CD4+ T cells to Th2 cells that produce IL-4, IL-5,

Patients with Netherton syndrome (NS), a severe ichthyosis in which affected individuals experience a significant predisposition for AD, have elevated levels of TSLP in their skin. Upregulated kallikrein (KLK) 5 in the skin of NS patients directly activates proteinaseactivated receptor 2 (PAR-2) and induces nuclear factor kappaB-mediated overexpression of TSLP, intercellular adhesion molecule 1, TNF-α, and IL-8. This phenomenon occurs independently of the environment, adaptive immune system and underlying epithelial barrier defect (Briot, et al., 2009, Briot, et al., 2010). *In vitro* study using human keratinocyte cell line HaCaT cells and reconstituted human epidermal layers transfected with filaggrin siRNA showed increased production of TSLP via toll-like receptor (TLR) 3 stimulation (Lee, et al., 2011). These findings suggest that reduced filaggrin levels may influence innate

immune response via TLR stimuli and elevate TSLP, leading to AD-like skin lesions.

AD is one of the emerging diseases in which epidermal dysfunction increases allergen and microbial penetration in the skin, with the consequent development of adaptive Th2 immune responses (Kondo, et al., 1998) within regional lymphoid tissue. The resultant Th2 cells may then home back to the skin or lungs, where they recognize allergen in the skin (McPherson, et al., 2010), which leads to local Th2 inflammation, reduced antimicrobial peptide expression (Nomura, et al., 2003), and filaggrin downregulation (Howell, et al., 2007). Indeed, the induction of circulating allergen-specific CD4+ T cells may be an important prerequisite underlying the pathogenesis of the atopic march (O'Regan, et al., 2009). Among moderate-to-severe AD patients, the *FLG* mutation carriers showed a greater number of house dust mite Der p1-specific IL-4 producing CD4+ T cells, suggesting that filaggrin mutations predispose to the development of allergen-specific CD4+ Th2 cells. The

Therefore, filaggrin deficiency is sufficient to impair epidermal barrier formation.

sensitivity to UVB-induced keratinocyte (KC) damage (Mildner, et al., 2010).

**2.3 Filaggrin and altered immunobiology**

and IL-13 (Ebner, et al., 2007, Soumelis, et al., 2002).

features of AD (Yoo, et al., 2005).

The above findings indicate the involvement of filaggrin in the development of AD. Therefore, the impact of filaggrin deficiency on cutaneous biological functions *in vivo* should be analyzed in detail. To address this issue, animal models are of great value.

Flaky tail mice (*Flgft*), first introduced in 1958, are spontaneously mutated mice with smaller ears, tail constrictions, and a flaking tail skin appearance (Lane, 1972). *Flgft* mice were outcrossed onto B6 mice at Jackson Laboratory (Bar Harbor, ME, USA) (Lane, 1972, Presland, et al., 2000) (Note: Although this strain was crossed with B6, it is not a B6 congenic strain but rather a hybrid stock that is probably semi-inbred). Homozygous *Flgft* mice have dry, flaky skin which expresses reduced amounts of profilaggrin mRNA and abnormal profilaggrin protein that is not processed to filaggrin monomers (Fallon, et al., 2009, Presland, et al., 2000).

Recently, it has been revealed that the gene responsible for the characteristic phenotype of *Flgft* mice is a single nucleotide deletion at position 5303 in exon 3 (5303delA) of the profilaggrin gene, resulting in a frameshift mutation and premature truncation of the predicted protein product. The copy number of the filaggrin repeat contained within this gene varies depending on the background strain. This mutant occurs in an allele with 16 copies of the filaggrin repeat (Fallon, et al., 2009).

*Flgft* mouse carries double gene mutation, *Flg* and matted (*ma*) in which the locations of the mutated genes are within close linkage to one another (Lane, 1972). The *ma* gene characteristic reported by Searle & Spearman (1957) causes the body-hair of affected mice to be brittle and inflexible, which results in longitudinal splitting and breaking due to friction against the cage and other objects. This mutation is a fully penetrant recessive house-mouse mutant which belongs to the "naked" category (i.e., a house-mouse with baldness resulting from the breaking of hairs or from hereditary hairlessness). This mutation can be identified morphologically by (1) erection of hairs, (2) matting of hair in clumps, (3) a tendency towards baldness, (4) a change from black- to brown-colored melanin in old hairs. The age at which this mutant is first identified based on external appearance varies from between two to four weeks (Jarret A, 1957, Searle A.G., 1957).

Recognition of the features of this mouse is more evident between 5 and 14 days of age when constricted, flaking tail skin and thickened short pinna of the ears are observed. In addition, *Flgft* mice are often smaller than their normal siblings at this age. Routine histological sections stained with hematoxylin and eosin showed that the stratum granulosum in *Flgft* mice at 1, 2, 4, and 8 days of age does not contain as many granular layers as that of non-*Flgft* mice (Lane, 1972). Mice of the *Flgft* genotype express an abnormal profilaggrin polypeptide that does not form normal keratohyalin F-granules and is not proteolytically processed to filaggrin. Therefore, filaggrin is absent from the cornified layers in the epidermis of the *Flgft* mouse (Fallon, et al., 2009, Presland, et al., 2000, Scharschmidt, et al., 2009). Consistently, we and others have described that *Flgft* mice express a truncated and smaller profilaggrin protein that is not processed to filaggrin (Fallon, et al., 2009, Moniaga, et al., 2010, Presland, et al., 2000) (Fig.1).

Flaky Tail Mouse as a Novel Animal Model of Atopic Dermatitis:

the gender of *Flgft* mice throughout the period (Moniaga, et al., 2010).

*Flgft* mice (Scharschmidt, et al., 2009).

scores (right panel)

Fig. 3. Characteristics of the clinical skin lesions.

Possible Roles of Filaggrin in the Development of Atopic Dermatitis 9

age (Oyoshi, et al., 2009), and the third contained no notice of any spontaneous dermatitis in

The fourth paper by Moniaga et al. have demonstrated that *Flgft* mice showed spontaneous dermatitis with skin lesions mimicking human AD as early as 5 weeks of age with mild erythema and fine scales and the cutaneous manifestations advanced with age in a steady state under SPF conditions (Moniaga, et al., 2010) (Fig. 2). The first manifestations to appear when mice were young were erythema and fine scaling; pruritic activity, erosion, and edema followed later (Fig. 3). In contrast, no cutaneous manifestation was observed in either C57BL/6 mice, studied as a control, or heterozygous mice intercrossed with *Flgft* and B6 mice kept under SPF conditions. There was no apparent difference in terms of clinical manifestations based on

Fig. 2. Clinical photographs of 20-week-old *Flgft* mice (left panel) and total clinical severity

Histological examination of the skin of *Flgft* mice stained with H&E revealed epidermal acanthosis, increased lymphocyte and mast cell infiltration and dense fibrous bundles in the dermis, in both younger (8-week-old) and older (18-week-old) *Flgft* mice; none of these conditions were observed in B6 mice (Fig. 4) (Moniaga, et al., 2010). These features were also reported in other studies (Fallon, et al., 2009, Oyoshi, et al., 2009) with more total cells,

Fig. 1. *Flgft* mouse has a truncated and smaller profilaggin and a lack of filaggrin protein.

#### **3.2 Flaky tail mouse and ichtyosis vulgaris**

Ichthyosis vulgaris (IV) is a heterogeneous autosomal skin disease characterized by dry and scaly skin, mild hyperkeratosis, and a decreased or absent granular layer that either lacks, or contains morphologically abnormal, keratohyalin granules (Manabe, et al., 1991). Several lines of evidences point to a genetic defect in a gene encoding *FLG* in IV. Immunoblotting studies showed that filaggrin protein was absent or markedly reduced in the epidermis of individuals with IV (Fleckman, et al., 1987, Sybert, et al., 1985). In line with this, it was proposed that *Flgft* mice could provide insight into the molecular basis of the filaggrindeficient human skin disorder IV. The epithelia of *Flgft* mice showed defects in tissue organization especially in the tail, an attenuated granular layer, reduced profilaggrin and a lacked of filaggrin granules in SC. In addition, keratinocytes culture from *Flgft* mice synthesized reduced amounts of profilaggrin mRNA and protein (Presland, et al., 2000).

#### **3.3 Flaky tail mouse in a steady state**

An early report demonstrated that *Flgft* mice without the *ma* mutation showed flaky skin as early as postnatal day 2, but became normal in appearance by 3 to 4 weeks of age without spontaneous dermatitis except for their slightly smaller ears (Lane, 1972). Later, the lack of filaggrin in the epidermis was proposed in the commercially available strain of *Flgft* mice, which has both *Flg* and *ma* mutations, as a model of IV, and therefore there was no discussion about the cutaneous inflammatory conditions from the perspective of AD (Presland, et al., 2000).

There have been four recent papers of *Flgft* mice as a model of filaggrin deficiency: the first paper used *Flgft* mice from which the *ma* mutation had been eliminated with four additional backcrosses to B6 mice (Fallon, et al., 2009), and the others used the commercially available *Flgft* mice (Moniaga, et al., 2010, Oyoshi, et al., 2009, Scharschmidt, et al., 2009). The first report showed only histological abnormality without clinical manifestation (Fallon, et al., 2009), and the second demonstrated spontaneous eczematous skin lesions after 28 weeks of

Fig. 1. *Flgft* mouse has a truncated and smaller profilaggin and a lack of filaggrin protein.

 Several lines of evidences point to a genetic defect in a gene encoding *FLG* in IV. Immunoblotting studies showed that filaggrin protein was absent or markedly reduced in the epidermis of individuals with IV (Fleckman, et al., 1987, Sybert, et al., 1985). In line with this, it was proposed that *Flgft* mice could provide insight into the molecular basis of the filaggrindeficient human skin disorder IV. The epithelia of *Flgft* mice showed defects in tissue organization especially in the tail, an attenuated granular layer, reduced profilaggrin and a lacked of filaggrin granules in SC. In addition, keratinocytes culture from *Flgft* mice synthesized reduced amounts of profilaggrin mRNA and protein (Presland, et al., 2000).

An early report demonstrated that *Flgft* mice without the *ma* mutation showed flaky skin as early as postnatal day 2, but became normal in appearance by 3 to 4 weeks of age without spontaneous dermatitis except for their slightly smaller ears (Lane, 1972). Later, the lack of filaggrin in the epidermis was proposed in the commercially available strain of *Flgft* mice, which has both *Flg* and *ma* mutations, as a model of IV, and therefore there was no discussion about the cutaneous inflammatory conditions from the perspective of AD

There have been four recent papers of *Flgft* mice as a model of filaggrin deficiency: the first paper used *Flgft* mice from which the *ma* mutation had been eliminated with four additional backcrosses to B6 mice (Fallon, et al., 2009), and the others used the commercially available *Flgft* mice (Moniaga, et al., 2010, Oyoshi, et al., 2009, Scharschmidt, et al., 2009). The first report showed only histological abnormality without clinical manifestation (Fallon, et al., 2009), and the second demonstrated spontaneous eczematous skin lesions after 28 weeks of

**3.2 Flaky tail mouse and ichtyosis vulgaris**

**3.3 Flaky tail mouse in a steady state**

(Presland, et al., 2000).

age (Oyoshi, et al., 2009), and the third contained no notice of any spontaneous dermatitis in *Flgft* mice (Scharschmidt, et al., 2009).

The fourth paper by Moniaga et al. have demonstrated that *Flgft* mice showed spontaneous dermatitis with skin lesions mimicking human AD as early as 5 weeks of age with mild erythema and fine scales and the cutaneous manifestations advanced with age in a steady state under SPF conditions (Moniaga, et al., 2010) (Fig. 2). The first manifestations to appear when mice were young were erythema and fine scaling; pruritic activity, erosion, and edema followed later (Fig. 3). In contrast, no cutaneous manifestation was observed in either C57BL/6 mice, studied as a control, or heterozygous mice intercrossed with *Flgft* and B6 mice kept under SPF conditions. There was no apparent difference in terms of clinical manifestations based on the gender of *Flgft* mice throughout the period (Moniaga, et al., 2010).

Fig. 2. Clinical photographs of 20-week-old *Flgft* mice (left panel) and total clinical severity scores (right panel)

Fig. 3. Characteristics of the clinical skin lesions.

Histological examination of the skin of *Flgft* mice stained with H&E revealed epidermal acanthosis, increased lymphocyte and mast cell infiltration and dense fibrous bundles in the dermis, in both younger (8-week-old) and older (18-week-old) *Flgft* mice; none of these conditions were observed in B6 mice (Fig. 4) (Moniaga, et al., 2010). These features were also reported in other studies (Fallon, et al., 2009, Oyoshi, et al., 2009) with more total cells,

Flaky Tail Mouse as a Novel Animal Model of Atopic Dermatitis:

and/or matted deficiency.

Oyoshi, et al., 2009).

al., 2009).

barrier disruption.

solution compared to its control littermate.

Possible Roles of Filaggrin in the Development of Atopic Dermatitis 11

The extent of severity of AD is known to be correlated with elevated serum IgE levels (Novak, 2009). Serum IgE and IgG1 levels in *Flgft* mice were significantly higher than those in control mice in the steady state under SPF conditions (Moniaga, et al., 2010, Oyoshi, et al., 2009). In addition, the numbers of CD4+ and CD8+ cells in the skin draining LNs in *Flgft* mice were significantly higher than those in control mice, but those of the spleen were similar for both groups. Thus, an enhanced cutaneous immune reaction seems to be induced in *Flgft* mice due to the condition of their skin induced by filaggrin

AD is thought to be mediated by helper T cell subsets, such as Th1, Th2, and Th17 (Bieber, 2008, Hattori, et al., 2010, Koga, et al., 2008). In the steady state, the skin of *Flgft* mice showed no difference of Th1 cytokine IFN-γ and Th2 cytokines IL-4 and IL-13 compared to the control. In contrast, there is a significant increase in mRNA expression of the Th17 cytokine IL-17, IL-17 promoting cytokines IL-6 and IL-23 (p19), and IL-17 inducible neutrophil attractant chemokine CXCL2 in *Flgft* mice (Moniaga, et al., 2010,

Since the barrier dysfunction is a key element in the establishment of AD, it is necessary to evaluate outside-to-inside barrier function from the perspective of invasion of external stimuli. Scharschmidt et al. reported increased bidirectional paracellular permeability of water-soluble xenobiotes by ultrastructural visualization in *Flgft* mice suggesting a defect in the outside-to-inside barrier. The ultrastructural visualization of tracer perfusion was analyzed by water-soluble, low molecular weight, electron-dense tracer lanthanum nitrate or fluorophore calcium green with enhanced penetration in *Flgft* mice. The data demonstrated that filaggrin deficiency leads to alterations in basal barrier function through a defect in the SC extracellular matrix and greater permeability through the same paracellular pathway that is used by water itself when exiting the skin (Scharschmidt, et

A new method for evaluating outside-to-inside barrier function quantitatively by measuring the penetrance of fluorescein isothiocyanate isomer 1 (FITC) through the skin has been developed (Moniaga, et al., 2010). The epidermis of *Flgft* mice contained a higher amount of FITC than that of B6 mice did (Fig.6 left panel). Consistently, fluorescence intensities observation in the epidermis of both mice showed stronger fluorescence in *Flgft* mice (Fig.6 right panel). In addition, the *Flgft* embryo was entirely dye permeable to toluidine blue

Another AD-like dermatitis model to test allergen priming of the skin in these mice was performed by application of ovalbumin (OVA) (Oyoshi, et al., 2009). Non tape-stripped skin of *Flgft* mice exposed to OVA exhibited significantly increased epidermal thickening, hyperkeratosis, spongiosis, acanthosis, and cellular infiltrates, as well as TEWL compared to control mice. mRNA levels for IL-17, IL-6, IL-23, IL-4, IFN-γ and CXCL2 but not IL-5 and IL-13 in the skin of *Flgft* mice after OVA exposure were significantly higher than those of control mice. The systemic immune response following cutaneous exposure revealed increased specific IgG and IgE to OVA, and splenocytes proliferated and produced OVAspecific Th1, Th2, Th17 and regulatory T cell cytokines (Fallon, et al., 2009, Oyoshi, et al., 2009). These findings demonstrate that *Flgft* mice tend to generate allergen-specific IgE and cytokine following cutaneous allergen challenge to the skin even without additional

**3.4 Flaky tail mouse showed enhanced percutaneous allergen priming**

lymphocytes, eosinophils, and mononuclear cells in *Flgft* mice compared to control mice. These data support the diagnosis of AD-like dermatitis in *Flgft* mice in the steady state under SPF conditions.

Fig. 4. Hematoxyllin and eosin (H&E)-stained sections in 8- and 18-week old mice. Scale bar, 100µm

Therefore, there exist discrepancies among the results of four recent papers on the cutaneous manifestation in the steady states. It seems to be related to the presence or absence of the *ma* mutation and/or variation in the genetic backgrounds of the different strains used, and to environmental factor. It has been reported that Japan carries a higher morbidity of AD than other countries (1998, Williams, et al., 1999), possibly due to environmental factors such as pollen. Because barrier dysfunction is a common characteristic of AD (Elias, et al., 2008, Nomura, et al., 2007, Palmer, et al., 2006), TEWL is commonly measured as an indicator of barrier function (Gupta, et al., 2008). TEWL was significantly higher in *Flgft* mice than in B6 mice from an early age (4 weeks) to an older age (16 weeks) (Fig. 5) (Moniaga, et al., 2010).

Fig. 5. TEWL through dorsal skin of 5-, 8-, and 16-week-old B6 and *Flgft* mice.

Flowcytometry analysis of cells isolated from ear skin confirmed that *Flgft* skin contained significantly increased percentages of CD4+ T cells and Gr-1+ neutrophils, but not CD11c+ dendritic cells, compared with ear skin from controls (Moniaga, et al., 2010, Oyoshi, et al., 2009).

lymphocytes, eosinophils, and mononuclear cells in *Flgft* mice compared to control mice. These data support the diagnosis of AD-like dermatitis in *Flgft* mice in the steady state under

Fig. 4. Hematoxyllin and eosin (H&E)-stained sections in 8- and 18-week old mice. Scale

Therefore, there exist discrepancies among the results of four recent papers on the cutaneous manifestation in the steady states. It seems to be related to the presence or absence of the *ma* mutation and/or variation in the genetic backgrounds of the different strains used, and to environmental factor. It has been reported that Japan carries a higher morbidity of AD than other countries (1998, Williams, et al., 1999), possibly due to environmental factors such as pollen. Because barrier dysfunction is a common characteristic of AD (Elias, et al., 2008, Nomura, et al., 2007, Palmer, et al., 2006), TEWL is commonly measured as an indicator of barrier function (Gupta, et al., 2008). TEWL was significantly higher in *Flgft* mice than in B6 mice from an early age (4 weeks) to an older

Fig. 5. TEWL through dorsal skin of 5-, 8-, and 16-week-old B6 and *Flgft* mice.

Flowcytometry analysis of cells isolated from ear skin confirmed that *Flgft* skin contained significantly increased percentages of CD4+ T cells and Gr-1+ neutrophils, but not CD11c+ dendritic cells, compared with ear skin from controls (Moniaga, et al., 2010, Oyoshi, et al., 2009).

SPF conditions.

bar, 100µm

age (16 weeks) (Fig. 5) (Moniaga, et al., 2010).

The extent of severity of AD is known to be correlated with elevated serum IgE levels (Novak, 2009). Serum IgE and IgG1 levels in *Flgft* mice were significantly higher than those in control mice in the steady state under SPF conditions (Moniaga, et al., 2010, Oyoshi, et al., 2009). In addition, the numbers of CD4+ and CD8+ cells in the skin draining LNs in *Flgft* mice were significantly higher than those in control mice, but those of the spleen were similar for both groups. Thus, an enhanced cutaneous immune reaction seems to be induced in *Flgft* mice due to the condition of their skin induced by filaggrin and/or matted deficiency.

AD is thought to be mediated by helper T cell subsets, such as Th1, Th2, and Th17 (Bieber, 2008, Hattori, et al., 2010, Koga, et al., 2008). In the steady state, the skin of *Flgft* mice showed no difference of Th1 cytokine IFN-γ and Th2 cytokines IL-4 and IL-13 compared to the control. In contrast, there is a significant increase in mRNA expression of the Th17 cytokine IL-17, IL-17 promoting cytokines IL-6 and IL-23 (p19), and IL-17 inducible neutrophil attractant chemokine CXCL2 in *Flgft* mice (Moniaga, et al., 2010, Oyoshi, et al., 2009).