**Author details**

Herring Shava\* and Willie Tafadzwa Chinyamurindi Department of Business Management, Faculty of Management and Commerce, University of Fort Hare, Alice, South Africa

\*Address all correspondence to<EMAIL_ADDRESS>
© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


*Edited by Nabil Kaddis Bissada*

Prostate Biopsy represents the standard procedure for diagnosing Prostate Cancer. This procedure can be performed transrectally, through perineum or occasionally through the urethra. Although the procedures of Prostate Biopsy are covered in numerous publications, there is still a need for gathering different aspects and methods in one source. Hopefully, this book will help physicians in their effort to provide the best treatment for their patients.

ISBN 978-953-307-702-4

Prostate Biopsy

Photo by HeitiPaves / iStock


**Pharmacology of Arterial Grafts for Coronary Artery Bypass Surgery**

Oguzhan Yildiz, Melik Seyrek and Husamettin Gul

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/54723


Preface

Land-use management stands at the crossroads of human development and environmental stewardship, shaping the landscapes that define our communities and the intricate ecosystems that sustain life. As we navigate an era marked by unprecedented global challenges, the importance of thoughtful and sustainable land-use practices has never been more evident.

This book, *Land-Use Management – Recent Advances, New Perspectives, and Applications*, is the result of collaborative efforts from a diverse array of experts who share a common passion for understanding, improving, and responsibly guiding the use of our terrestrial resources. In these pages, we aim to provide a comprehensive exploration of the latest advancements in land-use management, offering fresh perspectives and practical applications that reflect the evolving needs of our societies.

The journey begins with an acknowledgment of the complex interplay between human activities and the environment. We recognize the urgency to adopt innovative approaches that balance development with conservation, harness technology for sustainable outcomes, and embrace the principles of inclusivity and community engagement.

Each chapter within this book is a testament to the dynamism and interconnectedness inherent in effective land-use management. From the intricacies of urban planning to the sustainable practices transforming agriculture, and the integration of cutting-edge technologies, our contributors provide valuable insights into the multifaceted world of land use.

We invite readers to delve into these pages with an open mind and a curiosity for the possibilities that lie ahead. Whether you are a seasoned professional, a policymaker, an academic, or a concerned citizen, we hope this book serves as a valuable resource for understanding the complexities of contemporary land-use challenges and inspires collective action towards a more sustainable and resilient future.

May this exploration into recent advances, new perspectives, and practical applications in land-use management contribute to a broader conversation and drive positive change on a global scale.

This edited book consists of eleven chapters focusing on land-use management.

Chapter 1, "Assessing the Potential Flood Mitigation Services of a Former Golf Course with a Focus on Flood Storage", focuses on golf course closures in the United States since 2006, which present an opportunity for maximizing ecosystem services. A former course in Ohio was assessed for flood storage potential as part of future planning. Reversing culvert flow reconnected the stream to its floodplain. Monitoring, mapping, and two models estimated flood storage, revealing up to 103 K cubic meters and 2.1% of stormflow stored on the surface, with additional subsurface storage. The site also provides ecosystem services such as water purification, soil formation, and nutrient cycling.

Chapter 2, "Carbon Sequestration as a Land Management Strategy", examines the carbon sequestration in the AFOLU sector, which employs land management strategies (afforestation, restoration, soil carbon sequestration, and bioenergy) traded for payments in compliance and voluntary carbon markets. Compliance markets target national emissions reduction per international agreements, while voluntary markets involve governments and private sector engagement for global emission goals. Both face a common challenge: insufficient funding access for forest-dependent communities, impacting land management effectiveness.

Chapter 3, "How Far the Mono Transboundary Biosphere Reserve Protects Biodiversity in the Dahomey-Gap Corridor, West Africa?", describes how the Mono Transboundary Biosphere Reserve (MTBR), spanning Benin and Togo, faces anthropogenic pressures, necessitating prospective analysis for balanced biodiversity. Using land use and land cover (LULC) changes from 1986 to 2015, with Markovian chain analysis, this study predicts future LULC up to 2070. Urban/bare soil increased (8.79 ha/year) from 1986 to 2000, while mangroves expanded (9.81 ha/year) from 2000 to 2015. Projecting this dynamic, mangroves are expected to increase by 6% by 2070, but farmland may increase significantly (13%). Strengthening management strategies within MTBR is crucial for sustainable biological resource management.

Chapter 4, "Improving the Sustainability of Agriculture: Challenges and Opportunities", discusses how agricultural practices underpin global development and how unsustainable production may jeopardize future land capacity. Sustainable agriculture, hindered by issues like reliance on external inputs and climate change, offers a solution. Challenges include technology gaps and climate impacts. Proposed strategies involve reducing artificial fertilizer use, promoting local organic sources, and improving small-scale irrigation with environmental considerations. This chapter provides a brief overview of sustainable agriculture, its components, and challenges in achieving overall sustainability worldwide.

Chapter 5, "Integrated Effect of the Payment for Forest Environmental Services (PFES) in Vietnam", describes how the Payment for Forest Environmental Services (PFES) is a vital tool in global forest resource management, notably in countries like Vietnam. Instituted in 2010, the Vietnamese PFES policy enhances forest protection and livelihoods of forest-dependent communities. This chapter analyzes the PFES policy and evaluates its effectiveness in Ba Be district, Bac Kan province, focusing on environmental, economic, and social aspects. The synthesis highlights the overall positive impact of the PFES program in Vietnam and suggests solutions for its improvement and promotion in Vietnam and other developing nations globally.

Chapter 6, "Moving Horizon, Design Praxis through Soil Transformation: A Landscape Manifesto", describes how the moving horizon originates from a doctoral investigation, exploring the intricate relationship between landscape design and soil transformation. Emphasizing the dynamic nature of soil, the study asserts its pivotal role in landscape evolution. The soil, considered a live and dynamic material, shifts from the background to the foreground in both design practice and theoretical implications. The assessment results in ten propositions forming a landscape manifesto. The approach is applied in the Ravenna Climate Change Adaptation Plan, integrating soil understanding and transformation into territorial adaptation measures for climate change.

Chapter 7, "Perspectives and Application of Land Use Management Strategies to Address Mangrove Ecosystem Degradation in Guyana: A Case Study of Mon Repos", focuses on the coastal mangrove ecosystems in Guyana, which face persistent threats due to erosion, infrastructure development, and environmental degradation. Despite efforts, the National Mangrove Project Office's strategies, including public awareness, have not fully resolved the issues. This chapter advocates for zoning and regionalization effectiveness in combating mangrove degradation at Mon Repos, East Coast Demerara. Literature survey, document analysis, and ArcGIS Pro with remote sensing reveals potential positive impacts on ecosystem services, livelihoods, and waste management. However, a lack of real-time data hinders effectiveness, prompting recommendations for implementing strategies like geographic information systems, remote sensing, and a multiple-use conservation zoning plan.

Chapter 8, "Soil Evolution after Riparian Buffer Installation", describes how the Riparian buffers, engineered for water resource protection, aesthetics, and economic benefits, now showcase a novel role in preserving soil organic carbon. This review explores their support for ecosystem services and carbon sequestration potential and presents a case study from east-central Missouri. After 18 years, the riparian buffer exhibited 3.4% soil organic matter compared to 1.7% in the adjacent field, indicating significant carbon capture and preservation. Ammonium and sulfate concentrations were notably higher in the buffer, emphasizing its positive impact on habitat and soil water quality.

Chapter 9, "Threats and Sustainability of Brazil Nut (*Bertholletia excelsa* Bonpl.) Pre-Industrialization in the Amazon Region", describes how the Brazil nut (*Bertholletia excelsa*) is vital in the Amazon, but its seed production's climate change dynamics are poorly understood. Seed data spanning 1990–2021 in Baixo Amazonas revealed variable annual production (2156–10,235 tons), averaging 5192 tons. Linear regression showed no direct links between seed production and current-year climate variables (p > 0.05). However, significant associations emerged with prior-year climatic factors (p < 0.05), notably temperature, indicating a 1°C rise correlates with a 2595-to-2673-ton seed volume decrease. Temperature explains 38%–42% of seed volume variability, emphasizing the need to address global warming, enhance seed value processes, and cultivate climate-adapted *B. excelsa* varieties.

Chapter 10, "Towards Overcoming the Challenges to Adopting Ecosystem-Based Management Approach for Protected Areas: The Case of Serengeti Ecosystem", highlights how ecosystem-based planning is crucial for wildlife-protected areas, ensuring ecological integrity and wildlife survival. Most African protected areas were established before this approach, necessitating the adoption of ecosystem-based management (EBM) for ecological integrity and wildlife survival. The vast and complex Serengeti Ecosystem faces challenges, notably human–wildlife conflicts (HWCs). Despite various initiatives, the Greater Serengeti Conservation Society appears promising for successfully implementing EBM, addressing challenges for the Serengeti Ecosystem's sustainability.

Chapter 11, "Urban Planning and Land-Use Management in Jerusalem – Chronological Analysis: Urban Perspectives in Contested Cities", focuses on how Jerusalem's urban policies, shaped by four regimes (Ottoman rule, British mandate, Jordanian control, and Israeli occupation), reveal a complex spatial history. In less than 50 years (1917–1967), the city underwent transformative planning paradigms, impacting population and growth. These changes led to socio-spatial challenges, altering population composition and creating a paradoxical urban fabric. The successive authorities, culminating in the Israeli occupation, established intricate rules, resulting in a complex and spatially unsustainable planning system, exacerbating urban conflicts.

We hope this book will help readers navigate the intricate field of land-use management. This book aspires to be a guiding thread, weaving together the latest insights, diverse perspectives, and innovative applications. As we embark on this collective journey, may the pages that follow inspire a shared commitment to responsible stewardship, sustainable practices, and the harmonious coexistence of humanity and the environment.

> **Sérgio António Neves Lousada** UMa - Faculdade de Ciências Exatas e da Engenharia, Campus Universitário da Penteada, Funchal, Portugal


**Author details**

is being monitored. Power line noise is a very difficult problem in biological monitoring because the 50-or-60-Hz frequency is usually at the range of biological signal which could be monitored. Band-stop filters are commonly used to reduce the power line noise. The notch frequency in the band-stop filters is set to the power line frequency of 50 or 60Hz with the

The second type of noise is called inherent noise. Inherent noise arises from random processes that are fundamental to the operation of circuit's elements and thus is reduced by a good circuit design practice. While inherent noise is reduced, it can be never eliminated. Low-pass filters are used to reduce high-frequency components. However, noise signals within the frequency range of biological signals being amplified cannot be eliminated by this filtering approach.

Computer is a main device which is used to display the biological signals being monitored. However some low or high level languages such as machine language, FORTRAN, visual C+ +, MATLAB or LabView, have to be used to realize the operation on the acquisition data from biological body. When computers are used to acquire physiological data, programming instruction tell computer when acquisition data should begin, how often samples should be taken from how many sensors, how long acquisition data should continue, and where the digitized data should be stored. The rate at which a system acquires sample depends on the speed of computer clock's frequency and the number of computer instruction that could be completed in order to realize a sample. Of course, some computers are utilized to control the gain on the input amplifiers so that biological signals could be adjusted during data acquisition.

In this chapter, main biomedical sensors, devices and biological measurement systems are introduced to make readers understand present bioinstrumentation in market. The common biomedical sensors are narrated here to make readers grasp their basic sensing principle such as heart sound sensor, blood flow sensor and enzyme sensor. Furthermore, basic charge, current, voltage, power and energy used in biomedical engineering are explained to design some detecting circuits. Besides above, signal filters and operational amplifiers are also described and some advice or opinions are given out to give readers some available references. The basic detecting blocks of biomeasurement system are provided to quickly design relative bioinstrumentations. Readers need to carefully learn the content of biomedical sensors, signal

[1] Wang Baohua. Biomedical measurement and instrument [M]. China Fudan press, shanghai,

cutoff frequency located a few Hertz to either side.

In other systems, the gain of data acquisition has to be adjusted.

filters, operational amplifiers for bioinstrumentation.

**•** Computer

226 Advances in Bioengineering

**7. Chapter summary**

**Suggested reading**

January, 2009.

Gaofeng Zhou1\*, Yannian Wang2 and Lujun Cui1

\*Address all correspondence to<EMAIL_ADDRESS>
1 School of Mechatronic Engineering, Zhongyuan University of Technology, Zhengzhou, China

2 School of Information Engineering, Zhengzhou University, Zhengzhou, China


**7. The integration of palliative/holistic care in clinical and home-based care in terminally ill patients and the elderly**

Nurses are the most valuable member of the palliative care team who are in the best position to look into the physical, purposeful, social and spiritual needs of the patients, but in most situations, they (nurses) are not well-prepared to give the

*Suggestions for Addressing Clinical and Non-Clinical Issues in Palliative Care*

• High-interest rate—discouraging investors.

much will not be required from them.

security services.

• Fall in aggregate demand; fall in wages, income etc.

• Mass unemployment and general loss of confidence in the government [27]

Health is an essential part of man's existence even in the midst of economic depression. Before the current economic crisis, most present-day societies especially in the developing countries were still suffering disease epidemics while other nations incessantly experienced the endemic diseases affecting millions of lives. The global economic crisis persists to worsen the structure and purpose of the health sector. The economic depression has affected several segments of the economy including the health sector, contributing to low output, poor service delivery and poor health outcome. This has led so many people to resort to home care where so

The health sector is still struggling to provide rudimentary health care services with the collaborative efforts of government and individuals but determinations to realise this seem unfeasible due to the current state of the economy especially in the developing countries. The current economic position has affected health care funding and the level of support of the public and private health care services particularly among the rural poor is reduced due to increased proportion of poverty [28]. The economic predicament has contributed essentially to poor health outcome; it offers the occasion for careful government health modifications to improve the health system operation [28]. Health is directly or indirectly connected to other sectors such as food security and nutrition, family income generation, housing, education, employment status and other social

Following initial treatment for terminal diseases or elderly patients, they are usually given dates for followed-up appointment in hospital outpatient departments at steady intervals for routine checking in order to assess the patient and timely discovery of recurring of the ailment [29]. This method of follow-up places anxiety on the patient and their family members and most of them defaulted due to religious and cultural beliefs. Secondly, they may complain of inability to travel to the hospital, especially patients living in the rural communities. Most of these patients present late in the hospital either because of poor knowledge, cultural/ spiritual beliefs and non-availability of resources for prevention, diagnosis and treatment [28]. Patients and families are not well prepared after diagnosis about the diseases or palliation; this has led to most of the patients not responding to checkup appointments because they are not well informed and no form of follow-up

Based on the above premise, several countries have been able to put in place measures for providing home care services to a lot of their citizenry so as to alleviate the suffering of the poor masses. Most of the developing countries are still struggling as a result of poor economic position of these nations. Home care cannot be

From a nursing viewpoint, it is imperative to have information about the type of care needed, the explanations of care needed and quality of life among the elderly people and those diagnosed with terminal illnesses living in their own homes, in order to sustain their independence and make best use of their quality of life.

programmes are put in place to track these patients [29].

**6. The home care situation in a depressed economy**

instituted without adequate resources.

**258**

adequate care, especially to elderly and terminally ill patients. The main focus of nursing care as observed is curative approach without taking into consideration effective communication between them and patients/families the truth about diagnosis/prognosis of the disease, lack of patient and family readiness as a result of inadequate training/discharge planning and lack of follow-up [33].

Specifically, since there are no functional palliative care programmes in most health care facilities, the phases being addressed are:


**3. Maintenance and storage**

Short (working collection) and medium term storage facilities have been established at Plant Genetic Resources Institute (PGRI), NARC at Islamabad. Almost 60,000 seed samples (500 gm each) can be stored in the bank [27].

in thousands are selected from the progeny row block of the best representative families. Ginning out turn percentage and lint quality parameters are measured through high volume instrument (HVI) or conventional tools. Only the plants meeting the set standards (lint percentage=37.50%; staple length=28.00 mm; micronaire value=3.8-4.9 µg inch-1; fiber

Cotton Germplasm of Pakistan http://dx.doi.org/10.5772/58620 143

Seed from representative progenies are harvested followed by planting on bigger blocks (~ 0.5 acre). After comparing the yield and lint quality parameters of each of the progeny, families of the best progeny rows are selected for planting on bigger blocks (~10 hectares, depending upon the availability of seed). The seed harvested from the best blocks are multiplied by planting on large scale (1000s of hectares). The seed harvested from this block will make the foundation seed. It is usually accomplished at Govt Farms (preferably at seed corporation farms) or now on private sector farms under the patronage of private seed companies. This seed is exposed to another round of multiplication to raise certified seed which is disposed to farmers for raising the cotton crop. The area under each aforementioned multiplication step can be increased or reduced depending upon the demand of the seed by the farming com‐ munity. In Pakistan, 65,000 metric tons of cotton seed is needed every year for sowing on 3.2 million hectare. Of this 40-45% was provided through the formal seed sector (certified seed) until 2008. The informal seed sector, that includes farmers, breeders, and shopkeepers, are the major source of uncertified seed. Farmer-to-farmer sale is very popular among the farming community to provide seed to adjoining farms. Also the cotton growers retained a major portion of the seed produced at their own farms for planting in the next cotton growing season. In Pakistan, Plant Breeder Rights have not yet been enforced and the international seed companies, such as Monsanto, Bayer Crop Science and Biocentury, have major concerns pertaining loosing the legal protection of their products (transgenic events, varieties etc.). These are the major factors which hamper the establishment of a dynamic and robust seed

Under the umbrella of Ministry of Textile Industry, PCCC established in 1948, is considered as the prime research organization working on cotton encompassing economical, technological and agricultural research. Two main research institutes including Central Cotton Research Institute (CCRI) Multan, Punjab and CCRI Sakrand, Sindh are involved in multidisciplinary research encompassing, varietal development, improvement in all kind of agronomic practi‐ ces, combating insect pest and diseases, farmer's trainings etc. Under PCCC setup, seven other research stations or sub stations are involved in conducting research in specific area—largely on varietal development in collaboration with Provincial Setup. In total, 44 cotton varieties have been evolved by PCCC (Table 2). These varieties fulfill the requirement of spinners for

strength=>92,000 lb psi) are retained for planting progeny rows.

industry in Pakistan.

**4. Funding sources**

fineness and strength.

Collection of the crop germplasm is done either by undertaking plant collecting expedition trips or collected from researcher in the country or can be obtained from foreign countries. The health status of germplasm is analyzed upon its arrival and germination and moisture content are monitored. Before getting stored drying, packing and sealing of seed are done. These all activities meet the international standards. The current facilities were acquired through collaboration with Japan International Cooperation Agency (JICA), considering the interna‐ tional standards for seed preservation [27].

On the behalf of Federal Seed Certification & Registration Department, seeds of national approved varieties of cotton are stored at PGRI. At that time storage conditions of Pakistan Central Cotton Research Institute, Multan were not up to mark as PGRI recommendations, allowing medium term storage of genetic stock of cotton. Storage facilities for cotton germ‐ plasm at CCRI Multan have recently been established through Pak-US cotton productivity enhancement project (ID=1198). In total, ~30,000 accessions can be stored (Muhammad Idrees Khan, personal communication). This facility would help all cotton breeders for preserving their precious cotton germplasm.

In the botanical garden of CCRI, Multan, 28 cotton species of both cultivated and wild are maintained for utilizing in cotton breeding program of Pakistan.  All these belong to diploid wild species. Whereas, *G. tomentosum* 2 (AD)3, *G. mustelinum* 2(AD)4*, G. lanceolatum* 2(AD)4 and *G. darwinii* 2(AD)5 are found to belong from tetraploid wild species. Five *G. hirsutum* L. races viz. *latifolium, puncatum, morrilli, palmeri and marie-glante;* one *G. barbadense* L. race *braziliense* (kidney cotton); 13 diploid and 5 tetraploid hybrids; 5 triploid and 2 hexaploid hybrids; 3 pentaploid hybrids and 5 tri and 1 tetra species combinations are also maintained. In total, 62 grafts of out-standing *Gossypium* species and species hybrids were prepared for propagation purpose. These grafts were preserved under green house facility of CCRI Multan.

Though a varietal development procedure in Pakistan ensures enough purity, however, every year variants have been observed in the progenies of a variety developed through single plant selection because of limited natural cross pollination (up to 5%). Sometime, mutation and or mixing of seed during ginning process also contributes very small fraction to exaggerate the problem. In Pakistan, it has been observed that strict rouging is mandatory for maintaining the distinguished features of the variety every year, otherwise after three years the variety would appear like a mixture. In Pakistan, usually the maintenance work has been accom‐ plished so far at the respective breeding center of the variety. Representative plants preferably in thousands are selected from the progeny row block of the best representative families. Ginning out turn percentage and lint quality parameters are measured through high volume instrument (HVI) or conventional tools. Only the plants meeting the set standards (lint percentage=37.50%; staple length=28.00 mm; micronaire value=3.8-4.9 µg inch-1; fiber strength=>92,000 lb psi) are retained for planting progeny rows.

Seed from representative progenies are harvested followed by planting on bigger blocks (~ 0.5 acre). After comparing the yield and lint quality parameters of each of the progeny, families of the best progeny rows are selected for planting on bigger blocks (~10 hectares, depending upon the availability of seed). The seed harvested from the best blocks are multiplied by planting on large scale (1000s of hectares). The seed harvested from this block will make the foundation seed. It is usually accomplished at Govt Farms (preferably at seed corporation farms) or now on private sector farms under the patronage of private seed companies. This seed is exposed to another round of multiplication to raise certified seed which is disposed to farmers for raising the cotton crop. The area under each aforementioned multiplication step can be increased or reduced depending upon the demand of the seed by the farming com‐ munity. In Pakistan, 65,000 metric tons of cotton seed is needed every year for sowing on 3.2 million hectare. Of this 40-45% was provided through the formal seed sector (certified seed) until 2008. The informal seed sector, that includes farmers, breeders, and shopkeepers, are the major source of uncertified seed. Farmer-to-farmer sale is very popular among the farming community to provide seed to adjoining farms. Also the cotton growers retained a major portion of the seed produced at their own farms for planting in the next cotton growing season. In Pakistan, Plant Breeder Rights have not yet been enforced and the international seed companies, such as Monsanto, Bayer Crop Science and Biocentury, have major concerns pertaining loosing the legal protection of their products (transgenic events, varieties etc.). These are the major factors which hamper the establishment of a dynamic and robust seed industry in Pakistan.

#### **4. Funding sources**

**3. Maintenance and storage**

142 World Cotton Germplasm Resources

each) can be stored in the bank [27].

tional standards for seed preservation [27].

their precious cotton germplasm.

were preserved under green house facility of CCRI Multan.

Short (working collection) and medium term storage facilities have been established at Plant Genetic Resources Institute (PGRI), NARC at Islamabad. Almost 60,000 seed samples (500 gm

Collection of the crop germplasm is done either by undertaking plant collecting expedition trips or collected from researcher in the country or can be obtained from foreign countries. The health status of germplasm is analyzed upon its arrival and germination and moisture content are monitored. Before getting stored drying, packing and sealing of seed are done. These all activities meet the international standards. The current facilities were acquired through collaboration with Japan International Cooperation Agency (JICA), considering the interna‐

On the behalf of Federal Seed Certification & Registration Department, seeds of national approved varieties of cotton are stored at PGRI. At that time storage conditions of Pakistan Central Cotton Research Institute, Multan were not up to mark as PGRI recommendations, allowing medium term storage of genetic stock of cotton. Storage facilities for cotton germ‐ plasm at CCRI Multan have recently been established through Pak-US cotton productivity enhancement project (ID=1198). In total, ~30,000 accessions can be stored (Muhammad Idrees Khan, personal communication). This facility would help all cotton breeders for preserving

In the botanical garden of CCRI, Multan, 28 cotton species of both cultivated and wild are maintained for utilizing in cotton breeding program of Pakistan.  All these belong to diploid wild species. Whereas, *G. tomentosum* 2 (AD)3, *G. mustelinum* 2(AD)4*, G. lanceolatum* 2(AD)4 and *G. darwinii* 2(AD)5 are found to belong from tetraploid wild species. Five *G. hirsutum* L. races viz. *latifolium, puncatum, morrilli, palmeri and marie-glante;* one *G. barbadense* L. race *braziliense* (kidney cotton); 13 diploid and 5 tetraploid hybrids; 5 triploid and 2 hexaploid hybrids; 3 pentaploid hybrids and 5 tri and 1 tetra species combinations are also maintained. In total, 62 grafts of out-standing *Gossypium* species and species hybrids were prepared for propagation purpose. These grafts

Though a varietal development procedure in Pakistan ensures enough purity, however, every year variants have been observed in the progenies of a variety developed through single plant selection because of limited natural cross pollination (up to 5%). Sometime, mutation and or mixing of seed during ginning process also contributes very small fraction to exaggerate the problem. In Pakistan, it has been observed that strict rouging is mandatory for maintaining the distinguished features of the variety every year, otherwise after three years the variety would appear like a mixture. In Pakistan, usually the maintenance work has been accom‐ plished so far at the respective breeding center of the variety. Representative plants preferably

Under the umbrella of Ministry of Textile Industry, PCCC established in 1948, is considered as the prime research organization working on cotton encompassing economical, technological and agricultural research. Two main research institutes including Central Cotton Research Institute (CCRI) Multan, Punjab and CCRI Sakrand, Sindh are involved in multidisciplinary research encompassing, varietal development, improvement in all kind of agronomic practi‐ ces, combating insect pest and diseases, farmer's trainings etc. Under PCCC setup, seven other research stations or sub stations are involved in conducting research in specific area—largely on varietal development in collaboration with Provincial Setup. In total, 44 cotton varieties have been evolved by PCCC (Table 2). These varieties fulfill the requirement of spinners for fineness and strength.

The establishment of Punjab Agricultural Research Board (PARB) as an autonomous body under PARB Act, 1997 for fostering an integrated approach for research planning and efficient allotment of research resource so that the agriculture innovation system of the province can generate appropriate solutions of the issues faced to various stakeholders in the food and fiber chain [28]. The vision of the PARB is to support scientific innovations for the prosperity of Agricultural Stakeholders in Punjab. Ministry of Food, Agriculture and Livestock (MINFAL, desolved after 18th amendment) was also remained actively involved in improving agricul‐

Cotton Germplasm of Pakistan http://dx.doi.org/10.5772/58620 145

Presently, a project on cotton productivity enhancement has been initiated by the generous support of the U.S. Department of Agriculture, Agricultural Research Service; under agree‐ ment No.58-6402-0-178F (operating through ICARDA Pakistan). Major theme of the project revolves around the characterization of the various viral strains, screening of US cotton germplasm in Pakistan, transferring of new sources of resistance into adapted varieties of

A project "Sustainable Control of the Cotton Bollworm, *Helicoverpa armigera*, in Small-scale Cotton Production systems" was sponsored by the Common Fund for Commodities to be executed by China, India, Pakistan and UK. The overall objective of the project was to develop, apply, and disseminate cropping systems and pest management practices for cost-effective and sustainable control of the cotton bollworm *Helicoverpa armigera*. The project aimed to build on existing knowledge and experiences for the further development of efficient methods, resulting in substantially reduced uses of hazardous pesticides and increased profitability for

In Pakistan, germplasm (conventional) can be shared for utilizing in local cotton breeding programs without imposing any kind of restriction. However, for utilizing in breeding program outside the country, one must get permission from the developer provided the venture is commercially driven. However, two organizations like NIBGE and CEMB are involved in the introduction of alien genes through utilizing genetic engineering approaches. In this regard, for example, CEMB has restricted the utilization of its material through signing MTAs with the private seed companies. Similarly, these two organization also got their novel genes patented (national and or internationally) which itself restrict the use of the genetic

Since 1992, Pakistan is signatory to UN convention on biological diversity (CBD), ITPGRA, and International Technical Conference on Plant genetic Resources, Lipzig, Germany. Thus country grant permission for accessing PGR on jointly agreed provisions subjected to pre informed approval of contracting bodies. Also, the contracting bodies are supposed to share the results of research and developments and the benefits that are achieved by exploring such

tural studies in Pakistan by providing funds.

Pakistan, etc. [29].

cotton producers.

**5. Sharing**

material.

¥=Ginning out turn percentage; **€**=Thousand pounds per square inch

**Source:** Dr. Akhlaq Hussain, Description of cotton varieties of Pakistan 2004, Cotton Research and development Memoranda till 60's (Ed. Dr. Mahbub Ali), approval documents of cotton varieties released after 2004 and personal communication with breeders of the cotton varieties.

**Table 2.** List of approved *G. hirsutum* L. (upland cotton) varieties (non-GM) for Sindh

The establishment of Punjab Agricultural Research Board (PARB) as an autonomous body under PARB Act, 1997 for fostering an integrated approach for research planning and efficient allotment of research resource so that the agriculture innovation system of the province can generate appropriate solutions of the issues faced to various stakeholders in the food and fiber chain [28]. The vision of the PARB is to support scientific innovations for the prosperity of Agricultural Stakeholders in Punjab. Ministry of Food, Agriculture and Livestock (MINFAL, desolved after 18th amendment) was also remained actively involved in improving agricul‐ tural studies in Pakistan by providing funds.

Presently, a project on cotton productivity enhancement has been initiated by the generous support of the U.S. Department of Agriculture, Agricultural Research Service; under agree‐ ment No.58-6402-0-178F (operating through ICARDA Pakistan). Major theme of the project revolves around the characterization of the various viral strains, screening of US cotton germplasm in Pakistan, transferring of new sources of resistance into adapted varieties of Pakistan, etc. [29].

A project "Sustainable Control of the Cotton Bollworm, *Helicoverpa armigera*, in Small-scale Cotton Production systems" was sponsored by the Common Fund for Commodities to be executed by China, India, Pakistan and UK. The overall objective of the project was to develop, apply, and disseminate cropping systems and pest management practices for cost-effective and sustainable control of the cotton bollworm *Helicoverpa armigera*. The project aimed to build on existing knowledge and experiences for the further development of efficient methods, resulting in substantially reduced uses of hazardous pesticides and increased profitability for cotton producers.


**1. Introduction**

The structural design of buildings is meant to resist the anticipated loads likely to act on a structure. The structural designer chooses the structural system to resist gravity and lateral loads. There is a variety of simple and complex structural systems used to resist combinations of vertical gravity loads and earthquake actions. The techniques available nowadays to alleviate seismic actions are numerous. The requirements of continuous load paths in the vertical and horizontal directions, stiffness and strength, and ductility are well-known requirements for the proper seismic design of structures [1].

Structural systems employing shear walls, bracing and moment-resisting frames, and combinations of them are now widely used by designers. Analysis and design

of structures are guided by design codes and cover the most encountered needs and requirements of typical buildings. However, sometimes, building owners wish to make changes to their properties after the completed buildings are finished and occupied due to some unforeseen needs arising later on. Structural engineers are then consulted to execute the desired changes in the building. Some of the desired changes could produce changes to the overall structural behavior of the building. The designers are required to investigate thoroughly the new configuration of the building based on criteria and requirements of design codes originally used during the initial analysis and design stages. However, in many cases, such investigation is not performed, and a decision is finally taken to execute the desired changes without examining the structural safety of the new configuration of the buildings. The changes take many forms according to the needs arising. In one example, a new multi-story building is built beside an old and similar one and the owner decided to connect the two buildings by a corridor bridge for easy and fast circulation. In another example, a multi-story building is connected to a nearby high retaining wall in order to brace the retaining wall and provide it with ample lateral support against rotation and sliding. Other examples of adding or removing walls, partitions, beams, or even, columns, in order to suit the spaces of buildings to some new business needs are also encountered in practice. Partial or complete fatal collapses of buildings were reported due to arbitrary, nonengineered changes.

Many previous studies investigated the effects of connecting buildings together by sky bridges, sky pools, and sky gardens built of reinforced concrete or steel [2–10].

On the other hand, numerous theoretical studies on twin buildings linked by damping devices striving for mitigating seismic effects on the linked buildings have been conducted [11–14].

In this chapter, the following cases of changes to the dynamic properties of buildings are investigated. This chapter is organized into four parts.

First: Two or more adjacent buildings connected together by bridges after the buildings are completed and occupied for the purpose of easy circulation and saving of time and effort.

Second: Buildings connected by reinforced concrete beams to nearby high retaining walls in order to provide strong lateral support to the retaining walls.

Third: Theoretical investigation and structural analysis of connecting two or more buildings together by rigidly linked sky bridges and the effects of this linking on the seismic performance of the connected buildings.

Fourth: Theoretical investigation and structural analysis of connecting two or more buildings with special devices that are designed to mitigate seismic response and reduce earthquake effects on the connected buildings.

These parts are discussed in the next paragraphs.


**1. Introduction**

Interactions between proteins and nucleic acids mediate a wide range of processes within a cell from its cycle to the maintenance of cellular metabolic and physiological balance. These specific interactions are crucial for control of DNA replication and DNA damage repair, regulation of transcription, RNA processing and maturation, nuclear transport, and translation.

The characterization of protein-nucleic acid interactions is essential not only for understanding the wide range of cellular processes they are involved in, but also the mechanisms underlying numerous diseases associated with the breakdown of regulatory systems. These include, but are far from being limited to, cell cycle disorders such as cancer and those caused by pathogenic agents that rely on or interfere with host cell machinery. More recently, it has been hypothesized that many neurological disorders such as Alzheimer's, Huntington's, Parkinson's, and polyglutamine tract expansion diseases are a consequence, at least in part, of aberrant protein-DNA interactions that may alter normal patterns of gene expression (Jiménez, 2010).

The electrophoretic mobility shift assay (EMSA), also known as gel retardation assay, is a regularly used system to detect protein-nucleic acid interactions. It was originally developed with the aim of quantifying interactions between DNA and proteins (Fried & Crothers, 1981; Garner & Revzin, 1981) and since then evolved to be suitable for different purposes including the detection and quantification of RNA-protein interactions. EMSA is most commonly used for qualitative assays including identification of nucleic acid-binding proteins and of the respective consensus DNA or RNA sequences. Under proper conditions, however, EMSA can also be used for quantitative purposes including the determination of binding affinities, kinetics, and stoichiometry.

EMSA is a commonly used method in the characterization of transcription factors, the most intensely studied DNA-binding proteins, and the largest group of proteins in humans, second only to metabolic enzymes. Their purification and identification is crucial in understanding gene regulatory mechanisms. Transcription factors are sequence specific DNA binding proteins that are usually assembled in complexes formed prior to transcription initiation. They bind discreet and specific DNA sequences in the promoter

Electrophoretic Mobility Shift Assay: Analyzing Protein – Nucleic Acid Interactions 207

Since its first publication, in 1981, several improvements and variant techniques of EMSA were reported. Originally described as a method to qualitatively detect protein-DNA interactions, gel retardation assays rapidly became one of the most popular methods to map interaction sequences and domains not only in DNA but in RNA-protein interactions as well. EMSA was also adapted in order to allow the determination of quantitative parameters

Several features made EMSA one of the most popular methods among researchers that study protein-nucleic acid interactions. Probably, the main advantages of EMSA when compared to other methods, as we will further discuss in the next sections, may be considered as follows: (1) EMSA is a basic, easy to perform, and robust method able to accommodate a wide range of conditions; (2) EMSA is a sensitive method, using radioisotopes to label nucleic acids and autoradiography, it is possible to use very low concentrations (0.1nM or less) and small sample volumes (20 µL or less; Hellman & Fried, 2007). Even though, less sensitive, non-radioactive labels are often used as well. These labels can further be detected using fluorescence, chemiluminescence or immunohistochemical approaches. Although less sensitive then radioisotopes, the wide variety of labels that can be used makes EMSA a very versatile method; (3) EMSA can also be used with a wide range of nucleic acid sizes and structures as well as a wide range of proteins, from small oligonucleotides to heavy transcription complexes; (4) Under the right conditions a gel retardation assay can separate the distribution of proteins between several nucleic acids within a single sample (Fried & Daugherty, 1998) or distinguish between complexes with different protein stoichiometry and/or binding site distribution (Fried & Crothers, 1981); (5) Finally, but not less important, it is possible to use both crude protein extracts and purified recombinant proteins enabling the identification of new nucleic acid-

**2. Advantages and limitations**

including complex stoichiometry, binding kinetics and affinity.

interacting proteins or characterization of specific proteins and its targets.

Despite its sensitivity, versatility and usually easy to perform protocols, EMSA is often considered to bear a number of limitations. Dissociation can occur during electrophoresis since samples are not at equilibrium during the run, thus preventing detection. Additionally, complexes that are not stable in solution may be stable in the gel requiring very short runs so that the observed pattern relates to what happens in solution. EMSA does not provide a straightforward measure of the weights or entities of the proteins as mobility in gels is influenced by several other factors. Also, EMSA does not directly provide information on the nucleic acid sequence the proteins are bound to. However, this problem may usually be overcome using footprinting approaches as described further ahead. Kinetic studies using EMSA are limited since the time resolution for a regular EMSA protocol consists of the time required to mix the binding reaction and for the electrophoretic migration to occur before the mix enters the gel. Only processes that have relaxation times

larger than the interval required for solution handling are suitable for kinetic studies.

formation of protein-nucleic acid complexes alters these characteristics.

In this section, we will start with a simple account of the characteristics of the electrophoretic mobility of nucleic acids alone, and afterwards we will discuss how the

**3. How complexes migrate in gels**

region functioning either as an activator or repressor of expression of the targeted gene through protein-protein interactions (reviewed by Simicevic & Deplancke, 2010). Transcription factors play essential roles during development and differentiation. It is well established that disruption of normal function of tissue-specific transcription factors, as a result of mutations, is often associated with a number of diseases including most forms of cancer, neurological, hematological, and inflammatory diseases. Additionally, transcription factors are often found differentially expressed in different pathologies suggesting an at least indirect involvement on the onset or progression of diseases. One of the most prominent examples of the involvement of transcription factors in development and progression of diseases is perhaps the p53 protein. p53 is a transcription factor involved in the modulation of expression of several genes that regulate essential cellular processes such as cell proliferation, apoptosis, and DNA damage repair (reviewed by Puzio-Kuter, 2011). Mutations in p53 that cause loss of function were reported in about 50% of all cancers. It is believed that this loss of function makes cancer cells more prone to the accumulation of mutations in other genes thus facilitating and accelerating the formation of neoplasias (reviewed by Goh et al., 2011).

In our laboratory, research is mainly directed to the study of host-pathogen interactions during hepatitis delta virus (HDV) replication and infection. HDV is the smallest human pathogen so far identified and infects human hepatocytes already infected with the hepatitis B virus (HBV). Both viruses have the same envelope proteins that are coded by the HBV DNA genome. HDV is, thus, considered a satellite virus of HBV. The HDV genome consists of a single-stranded, circular, RNA molecule of about 1700 nucleotides. This genome contains only one open reading frame from which two forms of the same protein, the so-called delta antigen, are derived by an editing mechanism catalyzed by cellular adenosine deaminase I. Both forms, small and large delta antigen, were shown to play crucial roles during virus replication: the small delta antigen is necessary for virus RNA accumulation and the large delta antigen plays an important role during envelope assembly (reviewed by Rizzetto, 2009). However, neither protein seems to display any known enzymatic activity. Accordingly, HDV is highly dependent on the host cell machinery for virus replication. It has been shown through EMSA that the small delta antigen binds *in vitro* to RNA and DNA without any specificity, which is in agreement with one of the roles attributed to the protein as a chaperone (Alves et al., 2010). Making use of different experimental approaches it was possible to identify a number of cellular proteins that interact with HDV antigens or RNA (reviewed by Greco-Stewart & Pelchat, 2010). However, the precise role played by most host factors during the virus life cycle remains elusive. Furthermore, it is highly consensual among HDV researchers that many other cellular factors that interact with delta antigens or HDV RNA remain to be identified and it is crucial to find those that interact with HDV RNA for a better insight on its replication and as possible targets for new therapies.

In this chapter we will review the principles of EMSA and its advantages and limitations for the quantitative and qualitative analysis of protein-nucleic acid interactions. The key parameters influencing the quality of protein samples, binding to nucleic acids, complex migration in gels, and sensitivity of detection will be discussed. Finally, an overview of the principles, advantages and disadvantages of methods that are an alternative to gel retardation assays will be provided.


**5. Clinical results and register data**

The theoretical advantages of these improved implant surfaces need to be confirmed in patients. There are several clinical studies and several implants are monitored in arthroplasty registries. Because coated and standard implants are often used in different patient populations, a direct comparison of the implant performance is difficult. The more expensive implants with a surface modification or coating are more often used in patients with metal allergies. These patients have a high level of psychological distress when undergoing a TKA surgery [77], and it has been

suggested that anxiety is the main reason for less favorable results in these patients [28]. It is therefore likely that patients with allergies to implant materials have a higher overall risk for revision because of an unsatisfactory result after TKA. This needs to be considered when looking at arthroplasty registry data.

### **5.1 Clinical studies**

There are only a few studies comparing coated and standard implants. **Table 1** summarizes studies with a minimum 5-year follow-up. If the performance of the implant is the outcome of interest, coated and standard implants should be tested in similar patient populations. As it is difficult to randomize patients with allergies against implant materials, in most studies only patients without known allergies were included. This is not the target population for hypoallergenic implants, but investigation of the mechanical properties of implants in these patients is reasonable.

Studies are not available for all implants on the market. Published studies demonstrated no relevant differences between coated and standard TKA and overall good survival rates. Based on that data, modern coatings which have been tested in clinical studies seem to work well and there is no reason for concern. Because technologies are different, the published results cannot be transformed into different implants or coating technologies without additional clinical studies.

#### **5.2 Arthroplasty registry results**

The results of arthroplasty registries provide "real-world" information and are therefore an important source of data. However, it needs to be considered that, in most countries, patients who receive a coated TKA are somehow different from patients who receive a standard TKA, which results in patient groups with a different probability of revision. Therefore, as always with registry data, revision rates of an implant or implant group are not entirely be caused by the implant, but might also be influenced by the patient population.

There is a significant difference in the hazard ratio (HR) of revision between all the alternative surfaces (coatings and surface modifications) and standard CoCrMo femoral components in the Australian Arthroplasty Registry (AOANJRR). After 15 years, the CoCrMo implants have a revision rate of 6.3%, whereas the alternative surfaces have a revision rate of 9.4%. However, there are differences between the alternative surfaces. ZrN has lower revision rates than OxZr and TiN implants. After 5 years, the revision rate for the ZrN is 2.1% and for the uncoated components is 3.1%.

A review of more than 17,000 cases out of the AOANJRR evaluated outcomes of up to 12 years for the OxZr [88]. They found no significant difference for the 12-year cumulative percent revision (CPR) due to all causes (4.8% for CoCr and 7.7% for OxZr); non-septic causes, or osteolysis or loosening (0.6% for CoCr and 1.1% for OxZr). The only age-related difference was found with patients who were > 75 years old, for whom OxZr TKA had an increased CPR due to osteolysis or loosening.

In the National Joint Registry (NJR) of the United Kingdom, OxZr and ZrN have similar results in both versions [39]. AS Columbus (ZrN) had a cumulative revision rate of 2.42 compared to 2.05 of its uncoated version after 5 years. Genesis II Oxinium (OxZr) had a cumulative revision rate of 3.57 at 5 years and 7.67 at 15 years compared to the standard CoCr implants (2.05 at 5 years, 3.49 at 15 years). Both designs have a remarkably lower patient median age at primary TKA (AS Columbus 5 years lower, Genesis II

*Modern Coatings in Knee Arthroplasty DOI: http://dx.doi.org/10.5772/intechopen.105744*

*RCT = randomized controlled trial; TAS = Tegner activity scale; KSS = knee society score; and KSF = knee society function score.*

#### **Table 1.**

*Clinical studies involving monolayer and multilayer coatings as well as the OxZr surface modification.*

Oxinium 12 years lower). The younger age in TKA is a higher risk for earlier revision, which could explain the slightly higher revision rates of both designs in the register [38].

Hypoallergenic implants demonstrated higher overall revision rates in the German Arthroplasty Registry after 3 years [89]. In this report, the main differences between coated and standard implant groups were the higher rate of metal allergies in female

patients in the coated TKA group. Looking at the data in detail, it was recognized that for the most often used coated implants (Columbus, Vanguard, e.motion), there were no differences between coated and standard implants and that for these implants, revision rates were favorably lower than all implants. It seems that the higher revision rates are caused by less frequently used implants and that a general revision rate for "coated implants" is not sufficient. Each implant needs to be looked at separately.

An analysis of 62,177 primary TKAs from the Total Joint Replacement Registry in the USA compared OxZr to traditional CoCr TKA implants and showed no statistically significant higher risk for revision after a mean follow-up time of 2.8 years [90].


**4. Discussion**

To measure the motility of internal organs such as the stomach, a stretchable, batteryless and wireless strain sensor using resonant frequency modulation was investigated. This sensor can stretch up to 110% from its original length, shifting the resonant frequency by 6.2% at maximum around 13.56 MHz, which exceeds the strain ranges that have been measured wirelessly in previous studies [11–13]. Previous studies have shown that up to 80% strain can be measured wirelessly. However, to measure the stomach motility, the sensor must be able to detect a stretch of up to more than 100%, and thus, we have developed a sensor that can wirelessly measure strains up to 110%. The conductivity of the copper wire used in the present study (5.96 × 105 S/cm) [26] is higher than the conductivity of the materials used in previous studies, by about 9 to 4000 times (silver nano-ink: 1.5 × 102 S/cm [11], silver nanowire: 8.13 × 103 S/cm [12], and eGaIn: 3.4 × 104 S/cm [27]). In addition, since the Q increases as the coil resistance decreases [15], the sensor made of a copper wire developed in the present study has the advantage of maintaining a high Q for a wider range of strains than those reported in previous studies. This high Q of the proposed sensor was obtained through embedding the copper wire in silicone rubber sheet, unlike the other commonly employed methods to fabricate stretchable strain sensors based on thin metal films on thin substrates.

The sensor could detect the strain wirelessly at up to 22.5 mm distance by the used transceiver, although there is room for further improvement to increase the operating distance. Thus, our proposed sensor demonstrated that it satisfied the two contradictory requirements for wireless sensing of strains, namely, the high conductivity of the coil sensor and the high stretchability. Moreover, the maximum strain of the developed sensor was not inherently limited, but instead, originated from the limitation of the used experimental setup. One additional point to note is that we only investigated the resonant frequency modulation in response to strains in only one direction. For actual applications, however, bi-axial strains and bending would need to be applied. Previous studies show that there is a correlation

between the diameter of the coil pattern and the wireless sensing performance due to bending. The wireless sensing performance is less affected by the degree of bending of the sensor when the diameter of the coil sensor is smaller [13,28,29]. Thus, to minimize the bending effect caused by the curved surface of the stomach, the outer length of the coil pattern would need to be minimized. Also, to increase the distance of wireless sensing and the sensitivity, parameter optimizations would be needed, which include the reduction of the sensor thickness, the increase in the number of turns of the sensor to increase the degree of inductive coupling between the sensor and the transceiver, and the increase of the outer diameter of the transceiver.

To apply the developed sensor in a real application, misalignment between the sensor and the transceiver should be overcome. To minimize the misalignment effect, the transceiver is suggested to be large enough to cover the entire abdomen as illustrated in Figure 1a. By creating a magnetic field as uniformly as possible throughout the abdomen, the sensor can keep relatively constant coupling with the external transceiver even if the exact location of the sensor is unknown. As shown in Figure 1b, the distance between the sensor and the transceiver can be determined by knowing the distance from the abdominal surface to the sensor, which could be measured by a physician during the surgery or by a medical imaging method. Therefore, it would be possible to detect the deformation of internal organs such as the stomach. To minimize the variations in stomach conditions and posture, the patient would be asked to stay with a constant posture, e.g., laying down on a bed, during the detection. Also, checking the stomach motility would be performed a few days after the gastrectomy, in which duration the food intake is generally restricted and thus, the stomach condition is expected to be quite constant. However, all such aspects need further investigation including animal experiments.

**Author Contributions:** N.C. and S.K. conceived the idea. K.J.L. and N.C. fabricated the coils. K.J.L. and S.K. designed the experimental setup, analyzed the data, and wrote the paper. K.J.L. performed all the simulation and experiment.

**Funding:** This work was supported by the Basic Science Research Program (NRF-2017R1A2B2004598) and the BioMedical Fundamental Technology Development Program (NRF-2017M3A9E2056463) of National Research Foundation (NRF) of Korea.

**Conflicts of Interest:** The authors declare no conflict of interest.


**2. Mibyou, traditional, and current concepts**

Mibyou concept was established in ancient China more than 2000 year ago. The term was first appeared in one of the oldest Chinese medicine literature called "*Huangdi Neijing*" as a physiological condition that is not ill but not healthy [4]. It is important to treat the Mibyou before it progresses to diagnose endpoint diseases. Although this idea is quite valuable in today's preventive medicine, the Mibyou condition is hardly diagnosed by the routine clinical test to give specific disease name. The pathological definition of Mibyou was left obscure and has not been well accepted in the modern medicine, although the term Mibyou was reconfirmed and approved at the 7th Asian-Oceanian International Aging symposium in 2003. There are several efforts to identify the Mibyou condition, which are now progressed. For example, the group of Toyama University observed progressive change of gene expression in adipocyte for 3 months using genetically defined spontaneous metabolic syndrome model rat and found 147 genes showed characteristic change of expression pattern before metabolic syndromes developed [6].

On the other hand, recent development of clinical examination technologies such as biochemical assay-detecting disease markers in blood and also physical methods for imaging nidus such as MRI (magnetic resonance imaging), CT (computed tomography), and ultrasound echo allow us to detect diseases, even cancers at very early stage. In such stages of disorder, the patients can behave and enjoy the life activity as normal without hospitalization. The Japan Mibyou Association currently distinguished these early stages of diseases from the diseases that need medical care with hospitalization and defined them as modern Mibyou [7]. According to the newly proposed definition, there are two types of Mibyou, the western medicine Mibyou (Modern Mibyou) and the traditional oriental medicine Mibyou (Classical Mibyou), and the Modern Mibyou is further classified into two conditions, Mibyou I and Mibyou II as shown in **Figure 1**. The Mibyou I is such conditions that individuals feel uneasy or ill but clinical examinations including blood biochemical markers

#### **Figure 1.**

*Current Mibyou concept and Mibyou-Care for healthy life expenditure.*

*Mibyou Care is A Key for Healthy Life Elongation: The Role of Mibyou-Care Functional Foods DOI: http://dx.doi.org/10.5772/intechopen.101073*

or imaging check do not show detectable abnormality. On the other hand, Mibyou II is defined as the condition where individuals do not feel abnormality or ill and can spend regular daily life by keeping wellness but clinical examinations show some abnormal level of disease markers or the presence of some abnormal images.

According to this new definition of Mibyou, the Mibyou I covers the condition related to classical Mibyou and several uneasy symptoms such as anxiety, sleep defect, physical pains, overweigh, fatigue, and frail. The Mibyou II on the other hand covers many familiar disorders including obesity, hypertension, hyperglycemia, hyperlipidemia, diabetes, hyperuricemia, tiny stroke, latent cardiac failures, liver fat diseases, hepatitis virus B carrier, sarcopenia, and even early stage of cancers. By this categorization, such diseases as life style diseases and metabolic syndromes are covered by Mibyou II. This new definition of Mibyou provides more clear targets for Mibyou care practices.

#### **3. Mibyou care practices**

The health care targeting Mibyou (Mibyou-care practices) will be a reliable strategy to approach the healthy life span and to improve QOL (Quality of Life). The Mibyou I care, such as the daily behavioral habits carried out by normal healthy individuals for sustaining health, is especially important in the preventive medicine.

It is said that meal, physical excise, and brain activity (both mental and psychological) are the three factors sustaining health and wellness. Indeed, the Mibyoucare practices such as diet, exercises, acupuncture, Yoga, meditation, mental stimulation, and others are more or less related to or are targeting these factors.

The Mibyou II conditions are reflected in the disease markers such as blood sugar level, and thus are controllable by certain medical and nutritional intervention targeting these markers in collaboration with clinical stuffs. For example, diabetic condition could be managed by observing blood HBA1c level regularly as a diagnosed marker [8]. The Mibyou II-care practices for diseases prevention, amelioration, and stimulation of recovery include the actions such as remedy, nourishment, self-medication, and the medications assisted by co-medical stuffs such as physician, pharmacist, and nutritionist.

In these Mibyou care practices, the diet plays the most basic and essential part.

#### **4. Food functions**

Currently, the food functions are discussed by the following three categories. Those are 1: Nutritional, 2: Sensory, and 3: pharmacological functions [9]. The nutritional function is the basic property of foods functioning as the source of the building block for constructing body architecture (structures) and also the energy required for functioning the structure (activities). Foods usually accompany such sensory properties as taste, flavor, and color as well to stimulate appetite so that the nutrients are smoothly taken. The third category of food function is currently attracting extensive attention since a book of knowledge is getting accumulated that certain components existing in food ingredients often show pharmacological activity and they are called food factors [10]. The food factors are implicated as the very molecules taking part in the observed pharmacological functions of foods, especially of the foods traditionally used as folk medicine and the food for nourishing and astringent purpose [11].

Obviously, the nutritional and sensory roles of foods are playing essential roles in the Mibyou care, especially in Mibyou I care. On the other hand, the third role

of foods contributing to the medicinal functions of foods will take pivotal part in Mibyou II care.

The pharmacological function of foods is historically attracting much attention. "Foods are medicine" is well accepted in both oriental and western countries from ancient. One example is the oldest literature of herbs called "*Shennong bencaojing*" in China, in that 365 natural resources including botanicals, minerals, and animals were collected and classified into three categories according to their nutritional and pharmacological health benefits [12]. The listed first group is edible as food and suggested to eat routinely in the daily meals because of having potentials not only of nourishing and tonic functions but also elongating life span. The second group is not recommended to eat every day because of having a weak pharmacological activity, but is useful to ameliorate certain physiologically distorted conditions. The third group is toxic and is unable to eat, but often used as medicine to treat specific diseases.

These classifications of natural resources are interesting as reflected on the current category of the so called functional foods. The first group is the same as the dietary or nutritional supplements and the second group is overlapped to the so-called functional foods such as HOSHU, nutraceuticals, and pharmafoods. The third group is the medicine, and the resources in this group have been the target for developing clinical medicines or their prototypes [13].

From the view of the Mibyou care, the botanicals listed in the first and second categories of *Shennong bencaojing* are especially interesting, because they will be useful in functional application such as in the form of supplement and functional food.


4. Domain decomposition methods

Domain Decomposition Methods (DDM) encompass highly efficient algorithms to obtain solutions of large-scale discrete problems on parallel super-computers. They mainly consist of partitioning the domain into various subdomains and then getting the global solution through the resolution of the subdomain problems [12, 13] often in an iterative fashion. These methods can be seen as an iterative coupling by the internal and thus unknown BCS. There is a broad literature covering these approaches, and that is why this chapter, therefore, presents a short introduction for the sake of completeness. The recommended references include Bjorstad and Widlund [14], Bramble et al. and Marini and Quarteroni [15], who considered the Dirichlet-Neumann (DN) DDM and Neumann-Neumann.

Let L be an abstract linear differential operator, such as the Laplace operator, for instance. The DN-DDM scheme implies solving a series of problems in the proper sequence that requires a coloring tool (see Figure 1).  Notice that the interface between subdomains is denoted by Γ. After one provides the initial guess on the primary variables on Γ, i.e., γk must be given, then one can solve the problem on the white subdomains (Dirichlet problems), which corresponds to step 1 in Eq. (25).

$$(1)\begin{cases} Lu\_1^{k+1} = f \text{ in } \Omega\_1\\ u\_1^{k+1} = 0 \text{ on } \partial\Omega\_1 \cap \partial\Omega\\ u\_1^{k+1} = \gamma^k \text{ on } \Gamma \end{cases} \qquad (2)\begin{cases} Lu\_2^{k+1} = f \text{ in } \Omega\_2\\ u\_2^{k+1} = 0 \text{ on } \partial\Omega\_2 \cap \partial\Omega\\ \partial\_n u\_2^{k+1} = \kappa^{k+1} \text{ on } \Gamma \end{cases} \tag{25}$$

Let the primary variable be called "displacements" and their gradient "tractions," i.e., normal derivative in the boundary. Then, the tractions on the interface Γ must be computed after first solving step 1 on the white subdomains. They are then passed through communication to solve the second step on the black subdomains, i.e., Neumann subdomains. On this latter, since the tractions are known on Γ, one can solve for unknown displacements to provide feedback

Figure 1. It depicts the DNDDM.

on the next iteration level. Both displacements and tractions are often over-relaxed to improve the convergence rate. The given relaxation parameters, referred in Eq. (26) as θD and θN, must lie between 0 and 1:

$$\begin{aligned} \kappa^{(k+1)} &= \left(-\theta^{N} \cdot \eth\_{n} \mu\_{1}^{k+1} + \left(1 - \theta^{N}\right) \cdot \eth\_{n} \mu\_{2}^{k}\right) \text{ on } \Gamma\\ \gamma^{(k+1)} &= \left(\theta^{D} \cdot \mu\_{2}^{k+1} + \left(1 - \theta^{D}\right) \cdot \mu\_{1}^{k}\right) \text{ on } \Gamma. \end{aligned} \tag{26}$$

referred to those references that cover the topics of computational geometry, in particular how to build these NURBS entities. Let MFEM be described for linear isotropic elasticity regarding

ð

ð

Linear Thermo-Poroelasticity and Geomechanics http://dx.doi.org/10.5772/intechopen.71873

> Ω f T � vdx

(27)

231

(28)

∂ΩN t T � vds þ

T � C � εð Þ u dx ; lð Þ¼ v

T � Φds ; ½ �¼ u uð Þ1 � uð Þ2 � �

where ϒ stands for the gluing condition among subdomain interfaces and the jump ½ � u on the

� � þ ϒ vh; Λh ð Þ¼ l vh ð Þ

the parameters in Eq. (28) are as follows: Φh represents the mortar space while vh corresponds to the weighting space and Λh is the Lagrange multiplier space, i.e., the linear combination of mortar functions, often polynomial functions, and Lagrange multiplier degrees of freedom. Let

M be a conforming partition of the so-called parametric space, Ω, whose image serves as the mortar's geometrical entity, i.e., curve or surface, composed of line-segments (n ¼ 2Þ or quadrilaterals (n ¼ 3). One takes the mortar space as a finite-dimensional subspace of the continu-

bilinear forms, a and ϒ defined in Eq. (27) below [2, 3],

ð

Figure 2. Ω1 is in the top, Ω2 is in the bottom, and the interface Γ is the bold curve.

Ω εð Þv

ð

Γ ½ � u

displacements is required to vanish in an integral or "weak" sense, thus:

(

a uh; vh

ϒ uh; Φh � � ¼ 0

a u; v � � ¼

ϒ u; Φ � � ¼

T h

ous Sobolev spaces, that is:

It happens that this approach requires at least a two-entry coloring tool or even more, i.e., there may be subdomains with mixed interfaces, colored as gray [12]. There is a lack of parallelism in the sense that black subdomains must wait for the white ones to communicate their tractions. An initial guess for tractions should be prescribed to mitigate this issue, but this latter is not feasible in most cases. A straightforward way to obtain an initial estimate for the multiplier γk is by computing the so-called coarse-run that implies solving the same problem in a coarser mesh and interpolating over Γ by using the smaller's problem FE space. The reader may refer to the literature [16, 17] for further reading and proof of convergence and also revise [2] for a more detailed description that includes implementation details, which this chapter omits for the sake of brevity.

### 5. The mortar FE method (MFEM)

The primary goal here is to extend MFEM to glue curved interfaces such as the one shown in Figure 2 where MFEM treats non-matching interfaces. The section first introduces a brief description of non-uniform rational B-Splines curves and surfaces (NURBS) in [2, 3, 18]. The reader is

Figure 2. Ω1 is in the top, Ω2 is in the bottom, and the interface Γ is the bold curve.

on the next iteration level. Both displacements and tractions are often over-relaxed to improve the convergence rate. The given relaxation parameters, referred in Eq. (26) as θD and θN, must

> kþ1 þ 1 � θD � u1 k on Γ:

It happens that this approach requires at least a two-entry coloring tool or even more, i.e., there may be subdomains with mixed interfaces, colored as gray [12]. There is a lack of parallelism in the sense that black subdomains must wait for the white ones to communicate their tractions. An initial guess for tractions should be prescribed to mitigate this issue, but this latter is not feasible in most cases. A straightforward way to obtain an initial estimate for the multiplier γk is by computing the so-called coarse-run that implies solving the same problem in a coarser mesh and interpolating over Γ by using the smaller's problem FE space. The reader may refer to the literature [16, 17] for further reading and proof of convergence and also revise [2] for a more detailed description that includes implementation details, which this chapter omits for

The primary goal here is to extend MFEM to glue curved interfaces such as the one shown in Figure 2 where MFEM treats non-matching interfaces. The section first introduces a brief description of non-uniform rational B-Splines curves and surfaces (NURBS) in [2, 3, 18]. The reader is

kþ1 þ 1 � θN � ∂nu2 k on Γ

(26)

κð Þ kþ1 ¼ �θN � ∂nu1

γð Þ kþ1 ¼ θD � u2

230 Finite Element Method - Simulation, Numerical Analysis and Solution Techniques

lie between 0 and 1:

Figure 1. It depicts the DNDDM.

the sake of brevity.

5. The mortar FE method (MFEM)

referred to those references that cover the topics of computational geometry, in particular how to build these NURBS entities. Let MFEM be described for linear isotropic elasticity regarding bilinear forms, a and ϒ defined in Eq. (27) below [2, 3],

$$\begin{aligned} a\left(\underline{\underline{u},v}\right) &= \int\_{\Omega} \underline{\underline{c}(\underline{\underline{u}})}^T \cdot \underline{\underline{C}} \cdot \underline{\underline{c}(\underline{\underline{u}})} d\mathfrak{x} \; ; \; l(\underline{\underline{v}}) = \int\_{\partial\Omega^{\mathbb{N}}} \underline{\underline{t}}^T \cdot \underline{\underline{v}} d\mathbf{s} + \int\_{\Omega} \underline{\underline{t}}^T \cdot \underline{\underline{v}} d\mathbf{x} \\\ \Upsilon\left(\underline{\underline{u}}, \underline{\underline{\underline{\underline{D}}}}\right) &= \int\_{\Gamma} \underline{[\underline{u}]}^T \cdot \underline{\underline{\underline{D}}} d\mathbf{s} \; ; \; \; \left[\underline{\underline{u}}\right] = \left(\underline{\underline{u}}^{(1)} - \underline{\underline{u}}^{(2)}\right) \end{aligned} \tag{27}$$

where ϒ stands for the gluing condition among subdomain interfaces and the jump ½ � u on the displacements is required to vanish in an integral or "weak" sense, thus:

$$\begin{cases} a(\underline{u}\_h, \underline{v}\_h) + \Upsilon(\underline{v}\_h, \underline{\Delta}\_h) = l(\underline{v}\_h) \\ \Upsilon(\underline{u}\_h, \underline{\Delta}\_h) = 0 \end{cases} \tag{28}$$

the parameters in Eq. (28) are as follows: Φh represents the mortar space while vh corresponds to the weighting space and Λh is the Lagrange multiplier space, i.e., the linear combination of mortar functions, often polynomial functions, and Lagrange multiplier degrees of freedom. Let T h M be a conforming partition of the so-called parametric space, Ω, whose image serves as the mortar's geometrical entity, i.e., curve or surface, composed of line-segments (n ¼ 2Þ or quadrilaterals (n ¼ 3). One takes the mortar space as a finite-dimensional subspace of the continuous Sobolev spaces, that is:

$$\mathcal{L}\_k\left(\overline{T}\_h^{\ M}\right) = \left\{\Phi \in L^2\left(\overline{\Omega}\right) \,:\, \forall \mathbf{e}^{\mathcal{M}} \in \overline{T}\_h^{\ M}, \Phi|\_{\boldsymbol{\varepsilon}^{\mathcal{M}}} \in \mathbb{P}\_k\left(\boldsymbol{e}^{\mathcal{M}}\right)\right\} \tag{29}$$

discretization in each subdomain, Pkð Þe , as well as mortar space Pk eM . It also utilizes piecewise linear polynomials for the space discretizations in all examples herein that were run on a MacBook Pro laptop equipped with an Intel(R) Quad-Core(TM) i7-4870HQ CPU @ 2.5 GHz and 16 GB of RAM. The author chose this laptop for the sake of convenience, in particular, the availability of debugging tools free of charge, such as the Microsoft Visual Studio Community.

The example is a manufactured problem where the solution is a priori chosen. Then, one substitutes the given pressure field in the governing partial differential equation to obtain the source term, i.e., loading, that reproduces the input field. The problem in strong form looks like:

where the domain of interest corresponds to the unitary square and Dirichlet BCS are enforced.

Figure 3 shows the pressure field that corresponds to the problem 6.1 whose discretization encompasses three subdomains: two of them (the top and bottom ones) consist of triangular meshes while the one in the middle was discretized by a regular Cartesian quadrilateral mesh.

The pressure field is on the right-top corner, and its horizontal derivative is in the bottom-left corner, while the discrepancy between the numerical and exact solutions, i.e., the absolute

¼ f in Ω ; p ¼ p0 on ΓD ¼ Γ, (33)

Linear Thermo-Poroelasticity and Geomechanics http://dx.doi.org/10.5772/intechopen.71873 233

p xð Þ¼ ; y xy � ð Þ� x � 1 ð Þ� y � 1 exp � x2 þ y2 ; K ¼ I: (34)

Aside, one can achieve some level of parallelism due to the multi-core technology.

6.1. Example 1: Two-dimensional steady state single-phase flow

�∇ � K∇p

The top-left corner of the figure shows the mesh that is employed.

The input pressure field is given by:

Figure 3. The MFEM solution to problem 6.1.

herein Pk eM � � stands for the space of polynomials of total degree less than or equal to k while Ck T h M � � represents test functions that are continuous along the edges of eM.

One can write in a matrix or algebraic form, Eq. (28) as:

$$
\begin{bmatrix}
\begin{bmatrix} k^{(1)} \\ & \end{bmatrix} & \begin{bmatrix} \mathbf{Y}^{(1)} \end{bmatrix}^{T} \\
\begin{bmatrix} \mathbf{0} \end{bmatrix} & \begin{bmatrix} k^{(2)} \\ \end{bmatrix} & -\begin{bmatrix} \mathbf{Y}^{(2)} \end{bmatrix}^{T} \\
\begin{bmatrix} \mathbf{Y}^{(1)} \end{bmatrix} & -\begin{bmatrix} \mathbf{Y}^{(2)} \end{bmatrix} & \begin{bmatrix} \underline{\mathbf{u}}^{(1)} \\ \underline{\mathbf{u}}^{(2)} \end{bmatrix} \\
\end{bmatrix} \cdot \begin{bmatrix} \underline{\mathbf{u}}^{(1)} \\ \end{bmatrix} = \begin{bmatrix} \underline{\mathbf{l}}^{(1)} \\ \underline{\mathbf{l}}^{(2)} \\ \end{bmatrix} \cdot \tag{30}
$$

The equation above corresponds to the so-called "saddle-point problem (SPP)." Notice that subdomains are only connected using the Lagrange multiplier Λ if they happen to be known (it is well-known that for elasticity, the multipliers are the unknown tractions on the interface), then one can decouple the system in Eq. (30) and then one just needs to perform subdomain solves. For the SPP (30), one may match displacements or tractions in the interface. The Dirichlet-Neumann scheme that the section presents is only a particular case of the most general Robin-Robin domain decomposition scheme [2, 3]. The rectangular matrices ϒð Þi � �, i ¼ 1…2, are denoted as projectors since they permit to map to and from the given mortar space [2, 3].

The following line integral defines the projector, for 2-D problems, as:

$$\Upsilon\_{ij}^{(k)} = \underset{\overline{\Omega}}{\int\_{\overline{\Omega}} \varphi\_j^{(k)}(\xi) \Phi\_i(\xi) \cdot \|d\_\xi \underline{\mathcal{L}}(\xi)\| \, d\xi}{} \tag{31}$$

where wð Þk j represents the global non-mortar side interpolation functions and Φi are the mortar space basis functions, while k k dξC is the length of the tangent vector associated to the B-Spline or NURBS curve. Similarly, 3-D problems imply:

$$\Upsilon\_{ij}^{(k)} = \iint \varphi\_j^{(k)} \left( \underline{\xi} \right) \Phi\_i(\underline{\xi}) \cdot \left| \left| \partial\_{\xi} \underline{\xi}(\underline{\xi}) \times \partial\_{\eta} \underline{\xi}(\underline{\xi}) \right| \right| d\xi \, d\eta \tag{32}$$

where ∂ξS � ∂ηS � � � � is the norm of the surface's normal vector. Particular quadrature rules to compute these integrals must be developed. The reader should refer to [3] for a detailed explanation including the proper algorithm in pseudo-code.

### 6. Numerical examples

The author implemented these FE models in the Integrated Parallel Finite Element Analysis program (IPFA) that is a C++ application whose main characteristics are described in [2, 12]. IPFA employs standard continuous Lagrange polynomials as shape functions for the space discretization in each subdomain, Pkð Þe , as well as mortar space Pk eM . It also utilizes piecewise linear polynomials for the space discretizations in all examples herein that were run on a MacBook Pro laptop equipped with an Intel(R) Quad-Core(TM) i7-4870HQ CPU @ 2.5 GHz and 16 GB of RAM. The author chose this laptop for the sake of convenience, in particular, the availability of debugging tools free of charge, such as the Microsoft Visual Studio Community. Aside, one can achieve some level of parallelism due to the multi-core technology.

### 6.1. Example 1: Two-dimensional steady state single-phase flow

Ck T h M � �

One can write in a matrix or algebraic form, Eq. (28) as:

232 Finite Element Method - Simulation, Numerical Analysis and Solution Techniques

½ � 0 k

ð Þ2 h i

ϒð Þ1 � � � ϒð Þ2 � � ½ � 0

kð Þ1 h i

Ck T h M � �

where wð Þk

where ∂ξS � ∂ηS � � �

6. Numerical examples

¼ Φ ∈L2 Ω

� � : ∀eM ∈T h

herein Pk eM � � stands for the space of polynomials of total degree less than or equal to k while

� ϒð Þ2 � �T

The equation above corresponds to the so-called "saddle-point problem (SPP)." Notice that subdomains are only connected using the Lagrange multiplier Λ if they happen to be known (it is well-known that for elasticity, the multipliers are the unknown tractions on the interface), then one can decouple the system in Eq. (30) and then one just needs to perform subdomain solves. For the SPP (30), one may match displacements or tractions in the interface. The Dirichlet-Neumann scheme that the section presents is only a particular case of the most general Robin-Robin domain decomposition scheme [2, 3]. The rectangular matrices ϒð Þi � �, i ¼ 1…2, are denoted

j represents the global non-mortar side interpolation functions and Φi are the mortar

� � � ∂ηS ξ � � � � �

� is the norm of the surface's normal vector. Particular quadrature rules to

space basis functions, while k k dξC is the length of the tangent vector associated to the B-Spline

� � � ∂ξS ξ

compute these integrals must be developed. The reader should refer to [3] for a detailed

The author implemented these FE models in the Integrated Parallel Finite Element Analysis program (IPFA) that is a C++ application whose main characteristics are described in [2, 12]. IPFA employs standard continuous Lagrange polynomials as shape functions for the space

represents test functions that are continuous along the edges of eM.

½ � 0 ϒð Þ1 � �T

as projectors since they permit to map to and from the given mortar space [2, 3].

Ω

wð Þk

The following line integral defines the projector, for 2-D problems, as:

ϒð Þk ij ¼ ð

Ω

explanation including the proper algorithm in pseudo-code.

wð Þk j ξ � �Φi ξ

or NURBS curve. Similarly, 3-D problems imply:

ϒð Þk ij ¼ ðð M; Φj

uð Þ1 uð Þ2 Λ

l ð Þ1 l ð Þ2 0

j ð Þ ξ Φið Þ� ξ k k dξCð Þ ξ dξ (31)

3 7

5� (30)

�dξdη (32)

2 6 4

2 6 4

eM ∈ Pk e M n o � � (29)

> The example is a manufactured problem where the solution is a priori chosen. Then, one substitutes the given pressure field in the governing partial differential equation to obtain the source term, i.e., loading, that reproduces the input field. The problem in strong form looks like:

$$-\nabla \cdot \left(\underline{\underline{K}} \nabla p\right) = f \quad \text{in } \Omega \; ; \; p = p\_0 \text{ on } \Gamma\_\mathcal{D} = \Gamma,\tag{33}$$

where the domain of interest corresponds to the unitary square and Dirichlet BCS are enforced. The input pressure field is given by:

$$p(\mathbf{x}, y) = \mathbf{x}y \cdot (\mathbf{x} - \mathbf{1}) \cdot (y - \mathbf{1}) \cdot \exp\left[-\left(\mathbf{x}^2 + y^2\right)\right]; \underline{\mathbf{K}} = \underline{\mathbf{I}}.\tag{34}$$

Figure 3 shows the pressure field that corresponds to the problem 6.1 whose discretization encompasses three subdomains: two of them (the top and bottom ones) consist of triangular meshes while the one in the middle was discretized by a regular Cartesian quadrilateral mesh. The top-left corner of the figure shows the mesh that is employed.

The pressure field is on the right-top corner, and its horizontal derivative is in the bottom-left corner, while the discrepancy between the numerical and exact solutions, i.e., the absolute

Figure 3. The MFEM solution to problem 6.1.

This slope agrees with the theory that predicts a rate of O h3=2 [2, 3]. However, the resulting slope is slightly lower because of numerical errors, such as quadrature and linear system

Linear Thermo-Poroelasticity and Geomechanics http://dx.doi.org/10.5772/intechopen.71873 235

Finally, Figure 5 shows pressure snapshots that represent four different Dirichlet-Neumann iteration levels evolving from left-to-right and top-to-bottom. The fact that no initial guess for pressure was provided explains the mismatch in the first snapshot. That is why one needs to eliminate discrepancies by running the process to match up those subdomains, i.e., the traction residual in the interface must vanish, which for this case occurs in just a handful of iterations. The stop criterion precisely involves the residual in the tractions in the interface that is required to fall below the given tolerance. For this particular problem, the iterative process spent six

This example analyzes a coupled flow and mechanics simulation in a reconstructed reservoir (RS) model with different meshes for the flow and mechanics physics [18]. The author proposed such a reconstruction workflow in [18] which permits this latter feature by computing a projection operator to mapping pressures from the original flow mesh into the so-called reference mechanics mesh. Toward that end, the example employs the slightly compressible flow formulation loosely combined with the mechanics model as shown in Eq. (15). The objective is to show a realistic field level RS compaction and subsidence coupled computation. The goal is thus working three different cases for the mechanics part in which one only changes the resolution of the reconstructed mechanics mesh in the pay-zone while preserving the mechanical properties constant as well as the geometry, BCS, and the depletion scenario. The exercise admits the actual static properties as being in the pay-zone such as porosity f and permeability for the isotropic case Kx ¼ Kz ¼ Ky as shown in Figure 6, whose depiction is three

solving errors.

iterations to achieve a residual lower than 10�6 [3].

6.2. Example 2: Coupled flow and mechanics

Figure 5. The numerical L2 convergence rate for problem 6.1.

Table 1. Meshes for example 6.1.

error, was rendered in the right-bottom corner. Table 1 represents the number of elements and points of each mesh from top to bottom. The mortars as geometrical entities correspond to two B-Splines interpolants (NURBS with all weights equal 1) that were constructed by interpolating a sinusoidal wave as the figure shows (see [3] for details). Thirty-two quadratic mortar elements per curve were utilized to glue these three subdomains. A direct frontal solver was used to solve the global SPP in Eq. (30) [3]. The results that are summarized on Figure 3 are in good agreement with the analytical solution. The absolute error against the correct answer is also displayed. The discrepancy is of the order of 10�4 . Notice that besides the example only matched the displacements on the interface, a good accordance is also obtained for the horizontal derivative.

Whether or not one utilizes the SPP approach, the local problems are completely disconnected. This fact can be exploited to reduce the computational time significantly. Indeed, these sub problems can be handled in separate threads using a shared memory approach, i.e., multithreading assembling. A convergence analysis was also performed, by successively running refined meshes [3] and by keeping a refinement ratio of 2:1 between subdomains. The exercise used a piecewise quadratic mortar space where the number of mortar elements equals the number of coarse edges in the non-mortar sides. It tackled meshes of size 8, 16, 32, 64, 128 and 256 respectively. Figure 4 displays the resulting convergence rate in a log � log plot. The slope of the least-squares straight line is 1.44143, where the coefficient of determination is R2 ¼ 84%.

Figure 4. Snapshots showing the evolution of the DN-DDM applied to problem 6.1.

This slope agrees with the theory that predicts a rate of O h3=2 [2, 3]. However, the resulting slope is slightly lower because of numerical errors, such as quadrature and linear system solving errors.

Finally, Figure 5 shows pressure snapshots that represent four different Dirichlet-Neumann iteration levels evolving from left-to-right and top-to-bottom. The fact that no initial guess for pressure was provided explains the mismatch in the first snapshot. That is why one needs to eliminate discrepancies by running the process to match up those subdomains, i.e., the traction residual in the interface must vanish, which for this case occurs in just a handful of iterations. The stop criterion precisely involves the residual in the tractions in the interface that is required to fall below the given tolerance. For this particular problem, the iterative process spent six iterations to achieve a residual lower than 10�6 [3].


2. Parameter *b* in *W*S

When designing the weightings in Equation (10), the desired system band was 20 Hz and *b* was 1.35. To analyze the influence of the parameter *b* on weighting function *W*S, the other parameters in the weightings were kept unchanged. By changing *b* from 0 to 1.5, the dynamics were calculated by the step response, which is shown in Figure 6. It is seen in Figure 6 that when parameter *b* was less than 0.1, with the increase in parameter *b*, the settling time decreased rapidly, while the overshoot almost remained unchanged. When parameter *b* was larger than 0.1, with the increase in parameter *b*, the settling time decreased very slowly, while the overshoot increased quickly. The steady-state error almost remained unchanged. It is seen in Equation (6) and Figure 3 that with the increase in *b*, the system bandwidth widened, resulting in the response speed accelerating and the overshoot increasing. Hence, it is recommended that a larger *b* should be used if one expects a faster response speed.

**Figure 6.** Effect of parameter *b* on *W*S. (**a**) Settling time; (**b**) overshoot; (**c**) steady-state error.

3. Parameter *c* in *W*S

The parameter *c* was changed from 0 to 1.5 to investigate its influence, while the other parameters in the weightings were kept unchanged. The dynamics were calculated by the step response, which is shown in Figure 7. It is seen that with the increase in parameter *c*, the settling time and the overshoot almost remained unchanged, while the steady-state error increased. Hence, it is recommended that the parameter *c* should be small enough to eliminate the steady-state error, which is very important to RTHS.

**Figure 7.** Effect of parameter *c* on *W*S. (**a**) Settling time; (**b**) overshoot; (**c**) steady-state error.


**7. Bioinformatics analysis of retinoid signaling components in CRC**

We extended our study of RA signaling in CRC herein by using bioinformatics to analyze expression and mutation of RA signaling genes in CRCs and identify RA pathway genes that predict CRC patient survival. We found that most genes in the RA pathway are overexpressed and many are mutated in CRC (**Figure 2**). This is consonant with our previous result showing that RAR, RXR and other RA signaling proteins are overexpressed in CRC, which parallels overpopulation of ALDH-positive SCs that occurs during CRC tumorigenesis [39, 46]. Moreover, we found that aberrant expression of many RA signaling proteins (10 of 27) predicted (p < 0.05) decreased survival of CRC patients (**Figure 3**). We refer the reader to the meta-analysis by Chen et al. [63] which reveals that increased ALDH also indicates a poor prognosis in CRC patients. These updated findings provide insight into the complexity of RA signaling mechanisms and how RA signaling, when dysregulated, contributes to the development of CRC.

**Figure 2.**

*Bioinformatics analyses of RA signaling genes in CRC, including overexpression (a) and mutations (b). Bioinformatics data derived from cosmic catalog of somatic mutations in cancer (https://cancer.sanger.ac.uk/ cosmic).*