**2.1 Air drying**

Air drying is a common method used in many industries, including the pharmaceutical industry, to remove moisture from a product or material. It involves the use of ambient air to remove moisture from the surface of the product, typically by evaporation.

The air-drying process involves exposing the material to be dried to a stream of dry, warm air. This air is typically circulated around the material to maximize

exposure and evaporation. The process is generally slow and can take several hours or even days depending on the size and thickness of the material being dried as shown in **Figure 3** [12].


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## **Meet the editor**

Dr. Sharma S. Prabhakar is a distinguished nephrologist currently at Texas Tech University Health Sciences Center, where he is a tenured professor in the Departments of Medicine and Cell Physiology and Molecular Biophysics, and the Chief of Nephrology Division and Vice Chairman, Department of Medicine. He is an established researcher examining pathophysiologic mechanisms of

diabetic nephropathy and of insulin resistance in vitro and animal models. In the area of clinical research he initiated and is the principal investigator of a number of clinical studies. Dr. Prabhakar has over 100 publications including original articles, reviews, book chapters and published abstracts in prestigious journals, such as the American Journal of Physiology, Journal of American Society of Nephrology, and Kidney International. He has recently published a reference book entitled "Advances in the Pathogenesis of Diabetic Nephropathy". In recognition of his excellence in practice of medicine, Dr. Prabhakar was awarded an endowed chair by the University Medical Center. He is active in several professional societies and organizations and is the current President of American Federation for Medical Research.

Contents

**Foreword IX**

**Part 1 Primary Glomerulopathies 1**

Chapter 2 **Focal Segmental Glomerulosclerosis 25**

Abdelaziz Elsanjak and Sharma S. Prabhakar

Dawinder S. Sohal and Sharma S Prabhakar

Chapter 3 **Membranoproliferative Glomerulonephritis 45**  Matthew C. Pickering and Joshua M. Thurman

Chapter 4 **Primary IgA Nephropathy: An Update in 2011 59**  Francois Berthoux and Amir Kamal Aziz

**Genetic Basis and Treatment Options 69**

**Part 2 Infectious Glomerulopathies and Related Disorders 111**

**Post-Infectious Streptococcal Glomerulonephritis 137**

Chapter 6 **Rapidly Progressive Glomerulonephritis 95**

Chapter 7 **Post-Infectious Glomerulonephritis 113**

Chapter 8 *S. pyogenes* **Infections and Its Sequelae 125**  L. Guilherme, S. Freschi de Barros

W. Michael McShan and Roya Toloui

A.C. Tanaka, M.C. Ribeiro Castro and J. Kalil

Dimitrios Kirmizis, Aikaterini Papagianni and Francesco Paolo Schena

Chapter 1 **Membranous Nephropathy 3**

Chapter 5 **IgA Nephropathy: Insights into**

Maria Pia Rastaldi

Gurmeet Singh

Chapter 9 **Insights from Genomics on**

**Preface XI**

## Contents

### **Foreword XIII**

**Preface XV**

	- **Part 2 Infectious Glomerulopathies and Related Disorders 111**

X Contents

Contents VII

Chapter 22 **Mild Forms of Alport Syndrome: Hereditary**

**Part 5 Miscellaneous Topics 437**

Gertruida van Biljon

Toshihiko Ishimitsu

Chapter 23 **Nephrotic Syndrome**

Chapter 24 **Blood Pressure Control**

Han-Seung Yoon and Michael R. Eccles

**in Children – Studies from South Africa 439**

**in Patients with Glomerulonephritis 455**

**Nephropathy in the Absence of Extra-Renal Features 417**

Daniel Fischman, Arvin Parvathaneni and Pramil Cheriyath

	- **Part 5 Miscellaneous Topics 437**

VI Contents

Chapter 10 **Atypical Clinical Manifestations of**

Vincent Ho and Jason Chen

Toru Watanabe

Marco Zaffanello

Chapter 16 **Mixed Hematopoietic**

Chapter 17 **Differential Diagnosis**

Mitra Naseri

**Part 4 Glomerular Disease in**

Chapter 19 **Diabetic Glomerulopathy 327**

Emiko Takeuchi

Chapter 14 **Lupus Glomerulonephritis 231**  Chi Chiu Mok

**Acute Poststreptococcal Glomerulonephritis 151**

Chapter 11 **Hepatitis C Virus Associated Glomerulonephritis 169**

Enrique Morales, Elena Gutierrez-Solis, Eduardo Gutierrez and Manuel Praga

Chapter 12 **Glomerular Pathology in Patients with HIV Infection 189**

**Part 3 Vasculitis and Autoimmune Glomerulopathies 207**

Chapter 13 **Henoch-Schönlein Purpura Nephritis in Childhood 209**

Chapter 15 **Anti-Glomerular Basement Membrane Disease 251** Kouichi Hirayama and Kunihiro Yamagata

**Chimerism Allows Cure of Autoimmune**

**of the Pulmonary-Renal Syndrome 291**

Chapter 18 **RPGN - Clinical Features, Treatment and Prognosis 299**

**Metabolic and Systemic Conditions 325**

Chapter 20 **Metabolic Syndrome Associated Kidney Damage 369**

Chapter 21 **Glomerulonephritis and the Cystic Fibrosis Patient 399**

**Glomerulonephritis: Its Potential and Risks 277**

Martin Kimmel, Niko Braun and Mark Dominik Alscher

Mahmoud Barazi, Harneet Kaur and Sharma Prabhakar

Hequn Zou, Yuxin Wang, Guimian Zou and Jianxin Wan

Daniel Fischman, Arvin Parvathaneni and Pramil Cheriyath

Foreword

Glomerulopathies - Etiology and Pathogenesis.

The study of the fundamental and clinical aspects of glomerular disease has expanded exponentially over the last several decades. Fresh insights into old clinico-pathological entities emerge frequently and continuously. New disease entities also arise as the sophistication of investigation expands. Novel disease-specific treatments are applied often with impressive results while older, more empiric therapeutic strategies are in a constant state of evaluation and re-evaluation. Thus a book dealing with recent advances in the field of glomerulopathies from both clinical and therapeutic aspects is a welcome addition to our knowledge base. *An Update on Glomerulopathies - Clinical and Treatment Aspects* builds on the background provided by An Update on

In 24 concise, focused and well-formulated chapters the broad scope of clinical and therapeutic aspects of primary and secondary glomerular disease is reviewed and updated. The Editor, Dr. Sharma Prabhakar has chosen both the topics and the authors wisely. The contributions will have great appeal and value to the practicing clinician who frequently must face diagnostic and management challenges in this arena of medicine. While not exhaustive in coverage, the topics included embrace an impressive breadth of clinical experience in these disorders. The contributions also examine contemporary issues in sufficient detail to serve as an excellent guide for the clinician as well as trainees in nephrology. *An Update on Glomerulopathies - Clinical and Treatment Aspects* illustrates how far we have come in our understanding of clinical issues in glomerular disease, but also shows how much more needs to be understood.

**Richard J. Glassock, MD, MACP**

Laguna Niguel, California

USA

## Foreword

The study of the fundamental and clinical aspects of glomerular disease has expanded exponentially over the last several decades. Fresh insights into old clinico-pathological entities emerge frequently and continuously. New disease entities also arise as the sophistication of investigation expands. Novel disease-specific treatments are applied often with impressive results while older, more empiric therapeutic strategies are in a constant state of evaluation and re-evaluation. Thus a book dealing with recent advances in the field of glomerulopathies from both clinical and therapeutic aspects is a welcome addition to our knowledge base. *An Update on Glomerulopathies - Clinical and Treatment Aspects* builds on the background provided by An Update on Glomerulopathies - Etiology and Pathogenesis.

In 24 concise, focused and well-formulated chapters the broad scope of clinical and therapeutic aspects of primary and secondary glomerular disease is reviewed and updated. The Editor, Dr. Sharma Prabhakar has chosen both the topics and the authors wisely. The contributions will have great appeal and value to the practicing clinician who frequently must face diagnostic and management challenges in this arena of medicine. While not exhaustive in coverage, the topics included embrace an impressive breadth of clinical experience in these disorders. The contributions also examine contemporary issues in sufficient detail to serve as an excellent guide for the clinician as well as trainees in nephrology. *An Update on Glomerulopathies - Clinical and Treatment Aspects* illustrates how far we have come in our understanding of clinical issues in glomerular disease, but also shows how much more needs to be understood.

> **Richard J. Glassock, MD, MACP**  Laguna Niguel, California USA

Preface

knowledge from this reference book.

with current management strategies.

As the complexities of pathobiology of the glomerular diseases continue to unfold, the resultant scientific knowledge has lent itself to development of novel therapeutic targets and innovative preventive and therapeutic strategies. This book is a sequel to a similar one devoted to Etiology and Pathogenesis, and a broad discussion of advances in the clinical and treatment aspects of various glomerular disorders is the focus of this book. While most individual chapters serve as updates of clinical and treatment aspects of the respective glomerulopathies, they are by no means comprehensive discussion of these clincal conditions. The reader is referred to currents textbooks for the basic background clinical information of glomerulopathies and to enrich such

The book contains twenty four chapters divided conveniently into five sections. The first section deals with primary glomerulopathies and has six chapters. The first chapter is a rather comprehensive discussion on the clinical aspects of membranous nephropathy with a detailed review of the currently available treatment options. This is followed by a very exhaustive narrative of focal and segmental glomerulosclerosis with lucid illustrations. Membranoproliferative glomerulonephritis is a complex disorder which is also seen is several systemic conditions and is very elegantly discussed by Matthew Pickering et al. There are two chapters on IgA nephropathy, the most common glomerulopathy worldwide. Francois Berthoux et al. authored an excellent overall review of the clinical features and management of this condition, while Dimitrios Kirmizis et al. present a comprehensive review of the genetic determinants of IgA nephropathy. Finally, Maria Pia Rastaldi provides a crisp and clear discussion on the important subject of rapidly progressive glomerulonephritis

The second section is devoted to glomerulopathies complicating infectious conditions and includes six chapters. Gurmeet Singh authored a concise yet informative review on the postinfectious glomerulonephritis. In addition, there is a separate chapter on

## Preface

As the complexities of pathobiology of the glomerular diseases continue to unfold, the resultant scientific knowledge has lent itself to development of novel therapeutic targets and innovative preventive and therapeutic strategies. This book is a sequel to a similar one devoted to Etiology and Pathogenesis, and a broad discussion of advances in the clinical and treatment aspects of various glomerular disorders is the focus of this book. While most individual chapters serve as updates of clinical and treatment aspects of the respective glomerulopathies, they are by no means comprehensive discussion of these clincal conditions. The reader is referred to currents textbooks for the basic background clinical information of glomerulopathies and to enrich such knowledge from this reference book.

The book contains twenty four chapters divided conveniently into five sections. The first section deals with primary glomerulopathies and has six chapters. The first chapter is a rather comprehensive discussion on the clinical aspects of membranous nephropathy with a detailed review of the currently available treatment options. This is followed by a very exhaustive narrative of focal and segmental glomerulosclerosis with lucid illustrations. Membranoproliferative glomerulonephritis is a complex disorder which is also seen is several systemic conditions and is very elegantly discussed by Matthew Pickering et al. There are two chapters on IgA nephropathy, the most common glomerulopathy worldwide. Francois Berthoux et al. authored an excellent overall review of the clinical features and management of this condition, while Dimitrios Kirmizis et al. present a comprehensive review of the genetic determinants of IgA nephropathy. Finally, Maria Pia Rastaldi provides a crisp and clear discussion on the important subject of rapidly progressive glomerulonephritis with current management strategies.

The second section is devoted to glomerulopathies complicating infectious conditions and includes six chapters. Gurmeet Singh authored a concise yet informative review on the postinfectious glomerulonephritis. In addition, there is a separate chapter on the renal and non-renal sequelae of S pyogenes infections by Luiza Guilherme et al., while W. Michael McShan et al. provided a focused overview on the genomics of post streptococcal glomerulonephritis. The atypical clinical features of poststreptococcal glomerulonephritis are discussed in a chapter written by Toru Watanabe. Finally, there are two chapters that provide recent insights into glomerular complications of Hepatitis C and HIV infections respectively.

Preface XIII

USA

in a concise and clear manner the significance of and approaches to blood pressure

In summary, *An Update on Glomerulopathies - Clinical and Treatment Aspects* is a systemic overview of recent advances in clinical aspects and therapeutic options in major syndromes of glomerular pathology. While by no means this book replaces currently available textbooks in nephrology, it is the expectation of the Editor that it will form an excellent reference tool for practicing and academic nephrology community. The Editor expresses deep and sincere gratitude to all the authors for their valuable contributions which facilitated the prompt compilation of this invaluable resource.

**Sharma S. Prabhakar MD MBA FACP FASN**

Texas Tech University Medical Center

control in the context of glomerular disease.

Systemic autoimmune disorders and vasculitides constitute major causes of glomerular disease and often renal failure. The third section deals with such conditions and includes six chapters. Marco Zaffanello provided an excellent overview of the clinical aspects and management of Henoch-Schönlein Purpura in children, while Chi Chiu Mok reviewed the glomerular involvement in systemic lupus erythematosis in an elaborate manner. There are two other chapters covering other autoimmune conditions leading to glomerular disease, namely anti-glomerular basement membrane disease with a detailed description of the clinical features and management (Kouichi Hirayama et al.) and autoimmune glomerulonephritis with special focus on mixed bone marrow chimerism in the treatment (Emiko Takeuchi). Two other chapters discuss pulmonary renal syndrome, with Martin Kimmel et al. discussing the differential diagnosis of the condition in a chapter, while Mitra Naseri describes in the chapter, the rapidly progressive glomerulonephritis specifically leading to pulmonary renal syndrome.

The fourth section includes four chapters discussing the glomerular involvement in some major metabolic and systemic conditions. The first of these is diabetic glomerulopathy, which is the leading cause of renal failure resulting in end stage renal disease in the western hemisphere. This chapter is a very comprehensive review of pathogenesis and clinical features, besides being an exhaustive review of the currently available and emerging therapeutic options. Hequn Zou et al. wrote an excellent review on the glomerular involvement in a related disorder, the metabolic syndrome, a condition that is regarded by many as a distinct disease and is on the rapid rise to epidemic proportions. Daniel Fischman et al. authored a chapter on glomerular disease in cystic fibrosis, a systemic metabolic condition, while in another chapter, Han-Seung Yoon et al. reviewed milder forms of Alport syndrome, a hereditary glomerulopathy.

The final section has two chapters which relate to some general aspects of glomerular diseases. Gertruida van Biljon reviewed in a special chapter, glomerular disease leading nephrosis in children in South Africa. Finally, Toshihiko Ishimitsu described in a concise and clear manner the significance of and approaches to blood pressure control in the context of glomerular disease.

XII Preface

the renal and non-renal sequelae of S pyogenes infections by Luiza Guilherme et al., while W. Michael McShan et al. provided a focused overview on the genomics of post streptococcal glomerulonephritis. The atypical clinical features of poststreptococcal glomerulonephritis are discussed in a chapter written by Toru Watanabe. Finally, there are two chapters that provide recent insights into glomerular complications of

Systemic autoimmune disorders and vasculitides constitute major causes of glomerular disease and often renal failure. The third section deals with such conditions and includes six chapters. Marco Zaffanello provided an excellent overview of the clinical aspects and management of Henoch-Schönlein Purpura in children, while Chi Chiu Mok reviewed the glomerular involvement in systemic lupus erythematosis in an elaborate manner. There are two other chapters covering other autoimmune conditions leading to glomerular disease, namely anti-glomerular basement membrane disease with a detailed description of the clinical features and management (Kouichi Hirayama et al.) and autoimmune glomerulonephritis with special focus on mixed bone marrow chimerism in the treatment (Emiko Takeuchi). Two other chapters discuss pulmonary renal syndrome, with Martin Kimmel et al. discussing the differential diagnosis of the condition in a chapter, while Mitra Naseri describes in the chapter, the rapidly progressive glomerulonephritis specifically

The fourth section includes four chapters discussing the glomerular involvement in some major metabolic and systemic conditions. The first of these is diabetic glomerulopathy, which is the leading cause of renal failure resulting in end stage renal disease in the western hemisphere. This chapter is a very comprehensive review of pathogenesis and clinical features, besides being an exhaustive review of the currently available and emerging therapeutic options. Hequn Zou et al. wrote an excellent review on the glomerular involvement in a related disorder, the metabolic syndrome, a condition that is regarded by many as a distinct disease and is on the rapid rise to epidemic proportions. Daniel Fischman et al. authored a chapter on glomerular disease in cystic fibrosis, a systemic metabolic condition, while in another chapter, Han-Seung Yoon et al. reviewed milder forms of Alport syndrome, a hereditary

The final section has two chapters which relate to some general aspects of glomerular diseases. Gertruida van Biljon reviewed in a special chapter, glomerular disease leading nephrosis in children in South Africa. Finally, Toshihiko Ishimitsu described

Hepatitis C and HIV infections respectively.

leading to pulmonary renal syndrome.

glomerulopathy.

In summary, *An Update on Glomerulopathies - Clinical and Treatment Aspects* is a systemic overview of recent advances in clinical aspects and therapeutic options in major syndromes of glomerular pathology. While by no means this book replaces currently available textbooks in nephrology, it is the expectation of the Editor that it will form an excellent reference tool for practicing and academic nephrology community. The Editor expresses deep and sincere gratitude to all the authors for their valuable contributions which facilitated the prompt compilation of this invaluable resource.

#### **Sharma S. Prabhakar MD MBA FACP FASN**

Texas Tech University Medical Center USA

**Part 1**

**Primary Glomerulopathies**

## **Part 1**

**Primary Glomerulopathies**

**1**

*USA*

**Membranous Nephropathy**

Abdelaziz Elsanjak and Sharma S. Prabhakar

 *Department of Medicine, Texas Tech University Health Sciences Center*

Membranous nephropathy (MN), a very common cause of nephrotic syndrome, is a glomerulopathy defined histopathologically by the presence of immune complexes on the extracapillary side of the glomerular basement membrane (GBM). Idiopathic membranous nephropathy (IMN) is an antibody-mediated glomerular disease with no defined etiology, histologically characterized by uniform thickening of glomerular basement membrane (GBM), caused by subepithelial immune complex deposits. Most cases of MN are idiopathic, for instance approximately 75% of the cases of MN in developed countries are idiopathic, or primary membranous nephropathy (IMN). MN can be secondary to a wide spectrum of infections, tumors, autoimmune diseases or exposure to drugs or toxic agents. Examples include systemic lupus erythematosus, hepatitis B antigenemia or other chronic infections, and historically graft vs. host disease, sickle cell anemia, a number of drugs and toxins such

Idiopathic MN is a glomerulus-specific autoimmune disease and second only to focal glomerulosclerosis, is a leading primary cause of the nephrotic syndrome in adults. The name, '*membranous* nephropathy' reflects the pathological observation in light microscopy of thickening in the GBM between and around immune deposits that occur beneath the podocyte foot processes. The histological hallmarks of the disease were first described by Jones and Mellors and Ortega' over 60 years ago. These include "spikes," stained by methenamine silver, of normal GBM that extend between the immune deposits, a fine granular distribution of immunoglobulin (lg) G and the complement component C3 in a capillary-loop pattern revealed by immunofluorescence, and the presence of electron-dense subepithelial immune deposits indicated by electron microscopy (EM). Idiopathic MN most commonly occurs in patients between the ages of 30 and 60 years, with men twice as likely to be affected as women. However, MN does occur in children as well as in the very elderly. Up to 70% of patients present with the nephrotic syndrome and the others garner clinical attention due to abnormalities in urine sediment such as proteinuria. Microscopic hematuria is observed in up to 50% of cases although red cell casts are rare. Hypertension and impaired renal function are uncommon at the outset of the disease and are more likely to

Idiopathic membranous nephropathy (IMN) is an antibody-mediated glomerular disease that is histologically characterized by uniform thickening of glomerular basement membrane (GBM), caused by subepithelial immune complex deposits. The immune

as therapeutic gold salts, penicillamine, tumors, and agents containing mercury

**1. Introduction**

occur with disease progression

**2. Pathogenesis**


**2. Steam turbines control functions**

The speed regulation system is the primary control loop of the Automatic Generation Control (*AGC*) of an electrical system. The control of active power in a power system is accomplished primarily by controlling the torque of the machines primary drive system (Anderson & Fouad, 2003).

Figure 1 illustrates a system for regulating the speed of a steam turbine. By controlling the position xE of the control valve, a control can be exercised over the admission of steam (or water) at high pressure trough the turbine, and therefore the torque of the turbine. For a hydraulic amplifier, the input is the position of the pilot valve xD and the output is position xE of the main piston. A small downward movement of point E, the steam flow increases by an amount that, if measured in terms of power valve, represents an increment *Pv* . This increased flow is rendered by the increase in turbine power, *PT* .

Fig. 1. Example illustrating the mechanical speed control system of a steam turbine

The pilot valve XD, still in figure 1, can have its position changed, through the links or arms connection system, in three ways:

 Indirectly, by feedback due to changes in the position of the connection point B ( *B x* ), resulting from changes in speed.

Historically, *load-frequency primary controls* are part of the so-called *characteristics of speed governors*. However, the term "regulator" implies a mechanical speed sensor mechanically connected to control variations in input power, and since today most of the load-frequency controls are electro-hydraulic, speed control term does not describe generically this control function (Kundur, 1994).


**2. Background**

In this work, we adopted the PSD model [18] as the theoretical framework for our research, and the SQ model [9].

## **2.1 The PSD model**

The PSD model [18] is a recent conceptualization for designing, developing and evaluating persuasive systems. It consists of (a) the premises behind any persuasive system, (b) the persuasion context and (c) the persuasive software system features. Hence, according to the PSD model any persuasive system is based on eight premises detailed in [18] and listed here: P1: Useful; P2 User-friendly; P3: Unobtrusiveness; P4: Open for transparency; P5: Cognitive Consistency; P6: Incremental; P7: Information technology partiality; P8: Direct and indirect routes to persuasion.

The analysis of the *persuasion context* consists of looking into (1) the intent, (2) the event and (3) the strategy. The event comprises the use situation, user's characteristics, technological platform and environment. The strategy includes the message itself and the route to be used to achieve a goal.

The PSD model describes persuasive software system features grouped in four categories: (i) The **primary activity support category** focuses on supporting the activities that lead to achievement of the BCSS goals. These activities include

1 Systems in which software interacts with other software, systems, devices, sensors and people [14].

### *Negative UX-Based Approach for Deriving Sustainability Requirements DOI: http://dx.doi.org/10.5772/intechopen.96535*

reduction, tunneling, tailoring, personalization, self-monitoring, simulation and rehearsal. (ii) **Dialog support** refers to techniques/mechanisms to motivate users to use BCSS. This category includes praises, rewards, reminders, suggestions, similarity, liking and social role features. (iii) The **credibility category** relates to how to design a system so that it is more credible and thereby more persuasive. This category includes the following features: trustworthiness, expertise, surface credibility, real world feel, authority, third party endorsements, verifiability. iv) **The social influence category** describes how to design the system so that it motivates users by leveraging different aspects of social influence. The features that belong to this category are: social learning, social comparison, normative influence, social facilitation, cooperation, competition, recognition.

According to the PSD model, a behavior change can be divided into three categories:

The outcomes of these C, B and A-Changes are the formation, alteration or reinforcement:

### **2.2 The SQ model**

The SQ model [9] is defined in terms of four *sustainability dimensions*: (i) *Technical dimension* addresses the long-term use of software-intensive systems and their appropriate evolution in an execution environment that continuously changes. (ii) *Economic dimension* focuses on preserving capital and (economic) value. (iii) *Social dimension* focuses on supporting current and future generations to have the same or greater access to social resources by pursuing generational equity. (iv) *Environmental dimension* aims at improving human welfare while protecting natural resources. For software-intensive systems, this dimension aims at addressing ecologic concerns, including energy efficiency and ecologic awareness creation.

Each dimension is characterized by a set of *Quality attributes*, which can be interdependent. Such dependency can be of two types: (i) it is *inter-dimensional* if it relates a pair of quality attributes defined simultaneously in two different dimensions (e.g. security defined in the *technical* dimension can influence security in the *social* dimension); and (ii) it is *intra-dimensional* if a dependency exists between two different quality requirements defined within the same dimension (e.g. in the *technical* dimension, security may depend on reliability).

#### *Software Usability*

Our SQ model supports the identification of sustainability design concerns, and the quality assessment of software architecture. The list of measurable attributes of the SQ model and corresponding contributions to the four dimensions can be found at [9], which has been empirically evaluated [19, 20].


**Author details**

Aravind Kumar Jagadeesan1 \*, Krithiga Thangavelu2 and Venkatesan Dhananjeyan1

1 Department of Chemical Engineering, Sathyabama Institute of Science and Technology, Chennai, India

2 Department of Chemistry, Sathyabama Institute of Science and Technology, Chennai, India

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*Edited by Kirsi Tirri and Auli Toom*

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## Pedagogy in Basic and Higher Education Current Developments and Challenges

*Edited by Kirsi Tirri and Auli Toom*


2.3.1. Pixel-Based Method

This approach is analogous to at-site frequency analysis of extreme precipitation from rain gauge stations, which was originally applied by the NWS to establish the rainfall frequency isohyetal maps for the US [31]. Treating each 4-km × 4-km HRAP radar pixel as a single station, this is equivalent to considering the domain of study as a dense network of stations that are located 4 km apart from each other. At each pixel, the AMS sample of hourly precipitation, constructed from the 11-year radar dataset, is fitted to the GEV model and the parameters of the distribution are estimated at each pixel using the L-moment method. The quantiles corresponding to different return periods (e.g., 5, 10, 25, 50, 100) can then be estimated at each pixel using the GEV parameters. Confidence intervals for the pixel-based parameter and quantile estimates are constructed using the classical scalar bootstrap procedure suggested by Efron [32]. The bootstrap procedure is used to generate a large number of samples (500 in our case) for each individual pixel.

### 2.3.2. Regional Spatial Bootstrap Method

This is a probability weighted regional method that was originally proposed by Uboldi et al. [17] as a resampling approach for estimation of parameters of the AMS distribution. This technique is based on the generation of a regional sample at any desired location by taking into account data observed at surrounding stations but with decreasing importance when distance increases. Thus, the probability of contribution of a certain station decreases as it goes far away from the desired location. The probability of sampling also takes into consideration the length of the time series at each station, and as such, the possibility of oversampling can be avoided, and the use of short time series is enabled. This method is basically a spatial bootstrap technique in which a regional sample is generated repeatedly from the surrounding locations (pixels in the case of radar data) based on the randomness produced from the probability of data extracting. The procedure of this approach involves formation of a homogenous region, construction of a regional sample, estimation of statistical distribution parameters, repeating the regional sampling and parameter estimation several times as in any bootstrap technique, and finally obtaining a distribution of estimates for each parameter.

The regional sample of size (N) is constructed by extracting (N) observations randomly from all of the available data (M) in a homogenous region. The probability of extraction of each observation is assumed to be proportional to a prescribed Gaussian function (γm) of the distance between the station at the desired location (X) and any other station (Km). Using spatially continuous radar observations (pixel resolution of ~4 km in the current study), the spatial bootstrap methodology is implemented as follows. For each pixel at a desired location X, and by prescribing distance-dependent extraction probabilities, observations from nearby pixels are selected more often than observations from pixels located far away. The probability of extraction of the mth observation located at a pixel (Km) is given by the following relation:

$$\gamma\_{\rm m} = \exp\left\{ -\frac{1}{2} \left[ \frac{\mathbf{d}\_{\rm h}(\mathbf{X}, \mathbf{k\_{m}})}{\mathbf{D}\_{\rm h}} \right]^2 \right\}.\exp\left\{ -\frac{1}{2} \left[ \frac{\mathbf{d}\_{\rm v}(\mathbf{X}, \mathbf{k\_{m}})}{\mathbf{D}\_{\rm v}} \right]^2 \right\}\tag{7}$$

where dh(X, Km) and dv(X, Km) are the horizontal and vertical distance between pixel Km and the pixel at the desired location (X). The Dh and Dv are scale parameters that are selected to impose some degree of smoothing and were chosen in this study to be equal to the standard deviation of the available distances between (X) and (Km).

Normalized by the sum of probabilities of all the observations (M), the probability of extraction of each observation from N set of available observations can be obtained as follows:

$$\overline{\gamma}\_{\rm m} = \frac{\gamma\_{\rm m}}{\Gamma}, \Gamma = \sum\_{\rm m}^{\rm M} \gamma\_{\rm m} \tag{8}$$

By sorting the (M) observations in a descending order according to their probability of extraction (γ m) and assigning each observation a number (m) from 1 to M, a series of sequential ordered dataset is obtained. The cumulative normalized probability of extraction (γ m) of each observation ranges between (0, 1) and the probability of extraction of this cumulative probability is assumed to be uniformly distributed, i.e., (γ m)~U (0,1). A continuous random variable (ρ) is then used to implement a random number generator for a discrete random variable (m) with any prescribed (non-uniform) probability distribution on positive integers up to a generic M. By generating a random number (ρ), the corresponding cumulative probability (γ m) is equal to the generated random number (ρ) and realization number (m) is equal to the first observation that has cumulative probability greater than or equal to the generated probability (ρ).

The spatial bootstrap regional approach requires the formation of a homogenous region surrounding each pixel, from which a regional sample can be constructed. The identification of homogenous regions is a non-trivial step in the regional frequency analysis, and it may require subjective judgement [33]. A homogenous region is the area including a group of sites, or pixels as in the case of radar fields, that share similar physical characteristics. The advantages of working with a homogeneous region is that the historical data available within the region can be pooled to get an efficient estimate of parameters and hence a more robust quantile estimate [34]. Hosking & Wallis [33] strongly preferred to base the formation of homogenous regions on site characteristics (e.g., by using geographical delineation, cluster analysis, or principle components analysis) and to use the at-site statistics only in subsequent testing of the homogeneity of the proposed set of regions. Conventional regionalization techniques identify a fixed set of sites to form a contiguous region, resulting in fixed-boundary regions without smooth transitions.

Burn [10] presented the Region of Influence (ROI) approach for defining homogenous region, in which every site can have a potentially unique set of gauging stations to be used in the estimation of at-site extremes. The ROI technique is recommended as it avoids the transition problems across fixed boundaries by introducing smooth change in the estimates across the boundaries of the regions. The selection of the radius of influence is a trade-off problem, in which a large radius R will increase the number of sites included in each ROI, but at the expense of the homogeneity of the set of sites included. Conversely, a small radius R will ensure the homogeneity of the sites included, but the information transfer will be decreased due to the smaller number of sites. In this study, the ROI approach is applied by using a square window with an area equivalent to (2R + 1)2 bounding the pixel of interest (R is the radius of influence and is used here to refer to the number of pixels considered in the horizontal or vertical directions between the central pixel and the edge of the square window). The window forms a homogenous region and constructs the regional sample for the target pixel (central pixel) using the pixels lying inside this window.

Since the choice of a homogenous region, or the window size, should be based on climatic and physical characteristics, the US Climate Divisions are used in this study to provide an indication for the reasonable range of the radius of influence (R). Louisiana has nine Climate Divisions (Figure 1) and the average area of each climate division is approximately covering a window with side length of about 31 pixels, which corresponds to R = 15 pixels.

**Figure 1.** (**a**) Spatial distribution of the hourly Mean Annual Maxima (MAM; in mm). (**b**) The average month of AMS occurrence in each pixel. (**c**) The average 6-h of AMS occurrence in each pixel. Results are based on the period of study (2002–2012).

Therefore, we chose R = 15 as a threshold for identifying the homogenous regions to estimate PFE. In this study, we tested different square windows ranging from R = 3 pixels to R = 15 pixels (results are only shown for R = 5 and 10) to study the effect of the region size on the uncertainty of the estimates. For example, increasing the window size to 21 × 21, by setting R = 10 pixels, allows for many more pixels (M = 441 × 11; 441 pixels with AMS of 11 observations in each pixel) to be included in the region of each target pixel. The scale parameters in Equation (7), i.e., Dh and Dv, are chosen to be approximately equal to the standard deviation of each radius of influence (for R = 5, Dh = Dv = 1 pixel and for R = 10, Dh = Dv = 3 pixels). The regional sample size is chosen to be the same as the actual number of years available in the radar dataset, i.e., N = 11 (sampled out of the M observations).

In order to reduce the likelihood of extracting annual maxima that might come from the same event, a constraint is added in such a way that the gap in the time stamp of any two annual maxima extracted from two different pixels must be greater than 6 h. This criterion is evaluated using the Julian Date in which the 6 h represent 0.25 day. For instance, if the extracted annual maximum occurs in a certain Julian Date (JD), then any new annual maximum must have a new Julian Date greater than (JD + 0.25) or smaller than (JD − 0.25). This restriction might not be necessary in the case of gauge-based PFE analysis since the gauges are separated with relatively large distances, and therefore it is less probable to have annual series in two gauges that share exactly the same events. On the other hand, the application of this conditioned extracted annual maxima is critical to the radar-based annual maxima, since they are provided on a uniform grid with high spatial resolution (4-km × 4-km in our dataset).


**7. Mechanism of action for insecticidal property in leguminous plant**

Ureases from plants such as *G. max* (soy bean) and jack bean (JBU and *canatoxin*) are discovered to exhibit insecticidal activity in insects with cathepsin B-based (cysteine protease) and cathepsin D-based (aspartyl protease) digestive system. But no effect was observed in insects that relay on digestive enzymes which are trypsin-like [124, 125]. It is interesting to note that, no change was seen in the insecticidal effects of *canatoxin* and *G. max* ureases was after the enzyme was treated with an irreversible inhibitor of ureolytic activity, which indicate that ureolytic and insecticidal activities are not related [100]. In canatoxin, it was shown that its entomotoxic effect depends on an internal 10-kDa peptide (called pepcanatox), which is released by canatoxinhydrolysis by cathepsins in the digestive system of insects that are susceptible. Nonetheless, a 13-kDa recombinant peptide named jaburetox-2Ec, analog to pepcanatox, was cloned in *Escherichia coli* and was discovered to have insecticidal activity [126]. But with ureases from plant, there was no insecticidal activity seen in bacterial (*Bacillus pasteurii*) urease [100] and it was proposed that the entomotoxic peptide released from canatoxin by insect cathepsins is not present in ureases from microbes due to the subunit structure which is made up of two or three chains [100] and peptides that links and connect the different chains exhibit the insecticidal activity. Canatoxins has been studied extensively in several applications including industrial, agricultural, and medical [127]. Insect pest are the main cause of damage in agriculture having negative effect on commercially important crops globally. Having transgenic crops with intrinsic resistance to pest propose an alternative that is promising for chemical pesticides to prevent the crop losses [128]. Since plant ureases exhibit insecticidal property, to know their threedimensional structure and the structural basis of their mechanism of its endomotoxic peptide could be used effectively for the development of transgenic plants that are resistant to insects. From the industrial point of view, a large number of research papers have been published four decades ago in legumes urease immobilization studies. Legumes urease structural integrity and important resistance to chemical and thermal deactivation have been studied extensively for immobilization studies. Based on these facts, the present study reveals some details of leguminous canatoxin urease, which may be utilized by researchers to design better carriers for enzyme immobilization and areas by utilizing these plants.


**5. Sheep and goat yogurt**

In yogurt made from sheep milk as with those produced with cow milk, homogenisation increases product firmness and reduces product serum separation. Sheep yogurt is characterised by higher values of hardness, adhesiveness and extrusion, such factors are explained [31] by its high solids content.

 A research related with the analyses of the microstructure of goat, cow and sheep yogurts observed that in sheep yogurt the protein matrix of milk consists mainly of chains of large individual casein micelles. There were also small and regular voids. As a result, sheep milk produces a stronger gel that is more resistant to deformation [32]. Another study reports that sheep milk has a high viscosity that will influence the firmness of the product and may be caused by an increase in water binding capacity provided by its milk proteins [33]. Moreover, an investigation carried out by [34] shows that sheep milk is used in the production of mixed yogurts—goat milk was also used in the cases depicted—due to the higher amount of protein found in sheep milk that will improve the consistency of goat yogurt. On the other hand, some research [35] found out that goat yogurt has a poorer consistency, hardness and stability when compared, for example, with sheep and cow yogurt. In the case of the protein matrix, casein micelles of small size are bound in thick chains presenting large agglomerates as well as large empty spaces filled with serum or occupied by yogurt bacteria. This yogurt reveals a less compact gel and is therefore more delicate, brittle and less resistant to deformation. These properties affect the results of the instrumental analysis conducted on yogurt texture. This yogurt will then present low texture values and high syneresis values [30]. Several studies have been carried out on the low consistency caused by the presence of goat milk and [36], in a study based on samples of cow and goat milk yogurt and a mixture of the two, found out that as goat milk was added the firmness and consistency of the gel decreased.

The higher porosity of the protein network observed through the analysis of the microstructure and the subsequent lower degree of micellar aggregation also contribute to the mechanics observed, since a gel with low porosity is characterised by a compact matrix, which would contribute to increase the firmness and consistency of the gel. The poor firmness of the gel can still be influenced by the size of the fat globules and their mechanical properties as explained by [37] who reports a positive correlation between poor firmness and the smaller size of the globules.

Goat milk yogurt is less commercially produced, although it has high digestibility and good nutritional and organoleptic properties [6].