Author: Michael R. D'Andrea
Publisher: Academic Press
ISBN: 0128019883
Category : Science
Languages : en
Pages : 170
Book Description
Advances in Alzheimer's disease (AD) research have been challenging and without major breakthroughs in understanding its pathological basis. The reigning hypothesis suggests AD is the result of extracellular amyloid deposition that seed to form amyloid plaques, which then grow and kill neighboring neurons. However, there are several inconsistencies with this hypothesis, not to mention the inability to show clinical benefit in several failed clinical trials by pharmaceuticals (i.e., from Pfizer, Eli Lilly, etc.), and it is in the field's best interest to explore and test multiple hypotheses for pathology rather than drive the majority of research on this single amyloid theory. Reviewing many scientifically peer-reviewed publications, this book describes the "Inside-Out" hypothesis on how amyloid escapes the circulatory system through a dysfunctional blood-brain barrier to bind to the alpha 7 nicotinic acetylcholine receptor on pyramidal neurons. Over time, excessive amounts of amyloid appear to be internalized, resulting in neuron death and lysis. This simple mechanism readily explains plaque composition, size, shape, and location. Based on the current direction of research in the field, this hypothesis appears years from any research and development. - The clear, compelling, and unifying "Inside-Out" hypothesis of AD is brought to life through a string of scientific publications, synthesizing many known features of disease pathology - A high-level text on AD pathology, and suggestions for progress in a stagnating field - Point-by-point discussion on the issues surrounding the current amyloid cascade, and possible reasons why current clinical trials have failed - Contains high-quality photomicrographs in support of the "Inside-Out" hypothesis using single, double, and triple immunohistochemistry on human AD CNS tissues - Chapters address the need for a unifying plaque nomenclature, the importance of intracellular amyloid, the blood-brain barrier, inflammation, and autoimmunity
Bursting Neurons and Fading Memories
Author: Michael R. D'Andrea
Publisher: Academic Press
ISBN: 0128019883
Category : Science
Languages : en
Pages : 170
Book Description
Advances in Alzheimer's disease (AD) research have been challenging and without major breakthroughs in understanding its pathological basis. The reigning hypothesis suggests AD is the result of extracellular amyloid deposition that seed to form amyloid plaques, which then grow and kill neighboring neurons. However, there are several inconsistencies with this hypothesis, not to mention the inability to show clinical benefit in several failed clinical trials by pharmaceuticals (i.e., from Pfizer, Eli Lilly, etc.), and it is in the field's best interest to explore and test multiple hypotheses for pathology rather than drive the majority of research on this single amyloid theory. Reviewing many scientifically peer-reviewed publications, this book describes the "Inside-Out" hypothesis on how amyloid escapes the circulatory system through a dysfunctional blood-brain barrier to bind to the alpha 7 nicotinic acetylcholine receptor on pyramidal neurons. Over time, excessive amounts of amyloid appear to be internalized, resulting in neuron death and lysis. This simple mechanism readily explains plaque composition, size, shape, and location. Based on the current direction of research in the field, this hypothesis appears years from any research and development. - The clear, compelling, and unifying "Inside-Out" hypothesis of AD is brought to life through a string of scientific publications, synthesizing many known features of disease pathology - A high-level text on AD pathology, and suggestions for progress in a stagnating field - Point-by-point discussion on the issues surrounding the current amyloid cascade, and possible reasons why current clinical trials have failed - Contains high-quality photomicrographs in support of the "Inside-Out" hypothesis using single, double, and triple immunohistochemistry on human AD CNS tissues - Chapters address the need for a unifying plaque nomenclature, the importance of intracellular amyloid, the blood-brain barrier, inflammation, and autoimmunity
Publisher: Academic Press
ISBN: 0128019883
Category : Science
Languages : en
Pages : 170
Book Description
Advances in Alzheimer's disease (AD) research have been challenging and without major breakthroughs in understanding its pathological basis. The reigning hypothesis suggests AD is the result of extracellular amyloid deposition that seed to form amyloid plaques, which then grow and kill neighboring neurons. However, there are several inconsistencies with this hypothesis, not to mention the inability to show clinical benefit in several failed clinical trials by pharmaceuticals (i.e., from Pfizer, Eli Lilly, etc.), and it is in the field's best interest to explore and test multiple hypotheses for pathology rather than drive the majority of research on this single amyloid theory. Reviewing many scientifically peer-reviewed publications, this book describes the "Inside-Out" hypothesis on how amyloid escapes the circulatory system through a dysfunctional blood-brain barrier to bind to the alpha 7 nicotinic acetylcholine receptor on pyramidal neurons. Over time, excessive amounts of amyloid appear to be internalized, resulting in neuron death and lysis. This simple mechanism readily explains plaque composition, size, shape, and location. Based on the current direction of research in the field, this hypothesis appears years from any research and development. - The clear, compelling, and unifying "Inside-Out" hypothesis of AD is brought to life through a string of scientific publications, synthesizing many known features of disease pathology - A high-level text on AD pathology, and suggestions for progress in a stagnating field - Point-by-point discussion on the issues surrounding the current amyloid cascade, and possible reasons why current clinical trials have failed - Contains high-quality photomicrographs in support of the "Inside-Out" hypothesis using single, double, and triple immunohistochemistry on human AD CNS tissues - Chapters address the need for a unifying plaque nomenclature, the importance of intracellular amyloid, the blood-brain barrier, inflammation, and autoimmunity
Intracellular Consequences of Amyloid in Alzheimer's Disease
Author: Michael R. D'Andrea
Publisher: Academic Press
ISBN: 012804330X
Category : Psychology
Languages : en
Pages : 222
Book Description
Consequences of Intracellular Amyloid in Alzheimer's Disease addresses one of the more currently unresolved aspects confounding Alzheimer's research, the significance of intraneuronal amyloid. It seeks to explain some of the unresolved questions concerning intracellular amyloid and its origin, entry, and toxicity. Following up on Dr. D'Andrea's first book, Bursting Neurons and Fading Memories: An Alternative Hypothesis for the Pathogenesis of Alzheimer's Disease, this book further examines the Inside-Out or Bursting alternative hypothesis of how amyloid escapes the circulatory system to ultimately enter neurons, also examining whether there is a relationship between intracellular amyloid, amyloid plaques, and cognitive impairment. Through a comprehensive explanation of the currently relevant scientific research on intracellular amyloid compiled in this handy reference, readers will better understand the mechanisms that lead to neuron death. - Presents the latest research on the significance of intracellular amyloid as it relates to Alzheimer's - Addresses crucial questions about intracellular amyloid, including how if forms and enters neurons, its toxicity, if it triggers cell death, and how amyloid plaques are formed - Examines the potential relationship between intracellular amyloid, plaques, and cognitive impairment in an effort to answer whether Alzheimer's is initially a problem of amyloid, the neuron, or of the blood-brain barrier - Seeks to help researchers generate additional alternative therapeutic opportunities to cure Alzheimer's
Publisher: Academic Press
ISBN: 012804330X
Category : Psychology
Languages : en
Pages : 222
Book Description
Consequences of Intracellular Amyloid in Alzheimer's Disease addresses one of the more currently unresolved aspects confounding Alzheimer's research, the significance of intraneuronal amyloid. It seeks to explain some of the unresolved questions concerning intracellular amyloid and its origin, entry, and toxicity. Following up on Dr. D'Andrea's first book, Bursting Neurons and Fading Memories: An Alternative Hypothesis for the Pathogenesis of Alzheimer's Disease, this book further examines the Inside-Out or Bursting alternative hypothesis of how amyloid escapes the circulatory system to ultimately enter neurons, also examining whether there is a relationship between intracellular amyloid, amyloid plaques, and cognitive impairment. Through a comprehensive explanation of the currently relevant scientific research on intracellular amyloid compiled in this handy reference, readers will better understand the mechanisms that lead to neuron death. - Presents the latest research on the significance of intracellular amyloid as it relates to Alzheimer's - Addresses crucial questions about intracellular amyloid, including how if forms and enters neurons, its toxicity, if it triggers cell death, and how amyloid plaques are formed - Examines the potential relationship between intracellular amyloid, plaques, and cognitive impairment in an effort to answer whether Alzheimer's is initially a problem of amyloid, the neuron, or of the blood-brain barrier - Seeks to help researchers generate additional alternative therapeutic opportunities to cure Alzheimer's
Alzheimer’s Turning Point
Author: Jack C. de la Torre
Publisher: Springer
ISBN: 3319340573
Category : Medical
Languages : en
Pages : 256
Book Description
This compelling text provides an overview of the available technology for early detection and therapeutic management of vascular risk factors to Alzheimer’s before severe cognitive impairment symptoms appear. Chapters bring the reader from the trackless clinical research that has characterized Alzheimer’s progress for the last 20 years, to a nexus of new ideas and concepts that can change our outlook of this dementia. In-depth examinations of various hypotheses, preventive measures, current and prospective treatments are openly and clearly explored. The author discusses in depth his proposal of the vascular hypothesis of Alzheimer's disease which has become a mother-lode for basic and clinical studies and a key approach to the prevention of this dementia.Alzheimer’s Turning Point offers professionals, students and those looking to learn more about this disorder a fresh clinical perspective of this devastating disease.
Publisher: Springer
ISBN: 3319340573
Category : Medical
Languages : en
Pages : 256
Book Description
This compelling text provides an overview of the available technology for early detection and therapeutic management of vascular risk factors to Alzheimer’s before severe cognitive impairment symptoms appear. Chapters bring the reader from the trackless clinical research that has characterized Alzheimer’s progress for the last 20 years, to a nexus of new ideas and concepts that can change our outlook of this dementia. In-depth examinations of various hypotheses, preventive measures, current and prospective treatments are openly and clearly explored. The author discusses in depth his proposal of the vascular hypothesis of Alzheimer's disease which has become a mother-lode for basic and clinical studies and a key approach to the prevention of this dementia.Alzheimer’s Turning Point offers professionals, students and those looking to learn more about this disorder a fresh clinical perspective of this devastating disease.
Glia in Health and Disease
Author: Tania Spohr
Publisher: BoD – Books on Demand
ISBN: 1789852536
Category : Science
Languages : en
Pages : 164
Book Description
The book will highlight the role played by glial cells in the central and peripheral nervous systems in both healthy and unhealthy individuals. Among all processes involved, we will discuss the importance of the enteric nervous system in the control of gut homeostasis, in the interaction with the immune system, and its participation in pathological conditions such as metabolic syndrome. We will also look at the relevance of astrocytes during synaptic transmission and the regulation of plasticity by releasing gliotransmitters. Ultimately, we will highlight the influence of astrocytes during the development of a number of neurodegenerative diseases, such as multiple sclerosis and Alzheimer’s disease, focusing on how the serum levels of the astrocytic protein S100B can be used as a biomarker for clinical decisions.
Publisher: BoD – Books on Demand
ISBN: 1789852536
Category : Science
Languages : en
Pages : 164
Book Description
The book will highlight the role played by glial cells in the central and peripheral nervous systems in both healthy and unhealthy individuals. Among all processes involved, we will discuss the importance of the enteric nervous system in the control of gut homeostasis, in the interaction with the immune system, and its participation in pathological conditions such as metabolic syndrome. We will also look at the relevance of astrocytes during synaptic transmission and the regulation of plasticity by releasing gliotransmitters. Ultimately, we will highlight the influence of astrocytes during the development of a number of neurodegenerative diseases, such as multiple sclerosis and Alzheimer’s disease, focusing on how the serum levels of the astrocytic protein S100B can be used as a biomarker for clinical decisions.
Nanotechnology and Regenerative Medicine
Author: Maria H. Santana
Publisher: Academic Press
ISBN: 0323904327
Category : Science
Languages : en
Pages : 615
Book Description
"Cell niches are present in several human body tissues as a dynamic microenvironment essential to modulate stem cells' behavior in health, under injury, and in regenerative processes. The interplay between stem cells and their niche is necessary for sustaining tissues. The extracellular matrix (ECM) is the crucial component of the stem cell. It defines the architectural space, physical binding to the cell membrane, and interactions with the neighborhood cells and supports physical stress. Domains with nano or micrometric sizes define the surface and topology of the ECM, mediating cell interactions and macrophage recruitment to injured sites. Over the last two decades, the integration of biomedicine with other engineering and biomaterial sciences promoted the development of nanotechnology and regenerative medicine toward mimicking the specialized stem cell niches to treat diseases with less invasive and efficient therapies. Innovative approaches in nanotechnology, such as targeting the immunological system, transporting drugs across blood–brain/BBB and blood–retinal barriers/BRB, directing active moiety to specific disease location/organs, encapsulation of multiple components, and promoting signalization and pathway-specific surfaces for cell interactions and growth, are indeed promising. On the other side, developments of biomaterial scaffolds to mimic the cell niches for interactions with stem cells in vitro or in vivo have tremendous potential. The three-dimensional printing technology offers a base for a wide array of applications, for example, developing tissue constructs, mimetic organs, organoids, and organ-on-a-chip, thus avoiding the differences between animal model species and humans. Aiming closer to the natural environments, fresh autologous products from the blood, such as platelet-rich plasma (PRP), contain platelets and leukocytes, providing growth factors, cytokines, and proteins for the resident stem cells in the stages of regeneration. PRP also provides pain relief, reducing disabilities in elderly or diseased people. This book brings thought-provoking multidisciplinary topics on the diverse aspects of basic and applied sciences. The prime focus of the compilation is to understand the challenges researchers encounter in combining nanotechnology and regenerative medicine, ultimately integrating both disciplines for the benefit of the patient and offering them a ray of hope to be cured. - Presents multi-disciplined knowledge on bench-to-bedside application of nanotechnology in regenerative medicines - Highlights the fundamentals, frontiers, limitations, and challenges faced by regenerative medicines - Exhibits synergy of biotechnology, nanomedicine, biomedicine, chemical-material engineering, pharmaceutical technology, and applied medical sciences in success of regenerative medicines
Publisher: Academic Press
ISBN: 0323904327
Category : Science
Languages : en
Pages : 615
Book Description
"Cell niches are present in several human body tissues as a dynamic microenvironment essential to modulate stem cells' behavior in health, under injury, and in regenerative processes. The interplay between stem cells and their niche is necessary for sustaining tissues. The extracellular matrix (ECM) is the crucial component of the stem cell. It defines the architectural space, physical binding to the cell membrane, and interactions with the neighborhood cells and supports physical stress. Domains with nano or micrometric sizes define the surface and topology of the ECM, mediating cell interactions and macrophage recruitment to injured sites. Over the last two decades, the integration of biomedicine with other engineering and biomaterial sciences promoted the development of nanotechnology and regenerative medicine toward mimicking the specialized stem cell niches to treat diseases with less invasive and efficient therapies. Innovative approaches in nanotechnology, such as targeting the immunological system, transporting drugs across blood–brain/BBB and blood–retinal barriers/BRB, directing active moiety to specific disease location/organs, encapsulation of multiple components, and promoting signalization and pathway-specific surfaces for cell interactions and growth, are indeed promising. On the other side, developments of biomaterial scaffolds to mimic the cell niches for interactions with stem cells in vitro or in vivo have tremendous potential. The three-dimensional printing technology offers a base for a wide array of applications, for example, developing tissue constructs, mimetic organs, organoids, and organ-on-a-chip, thus avoiding the differences between animal model species and humans. Aiming closer to the natural environments, fresh autologous products from the blood, such as platelet-rich plasma (PRP), contain platelets and leukocytes, providing growth factors, cytokines, and proteins for the resident stem cells in the stages of regeneration. PRP also provides pain relief, reducing disabilities in elderly or diseased people. This book brings thought-provoking multidisciplinary topics on the diverse aspects of basic and applied sciences. The prime focus of the compilation is to understand the challenges researchers encounter in combining nanotechnology and regenerative medicine, ultimately integrating both disciplines for the benefit of the patient and offering them a ray of hope to be cured. - Presents multi-disciplined knowledge on bench-to-bedside application of nanotechnology in regenerative medicines - Highlights the fundamentals, frontiers, limitations, and challenges faced by regenerative medicines - Exhibits synergy of biotechnology, nanomedicine, biomedicine, chemical-material engineering, pharmaceutical technology, and applied medical sciences in success of regenerative medicines
Intracellular Consequences of Amyloid in Alzheimer's Disease
Author: Michael R. D'Andrea
Publisher: Academic Press
ISBN: 9780128042564
Category : Science
Languages : en
Pages : 0
Book Description
Consequences of Intracellular Amyloid in Alzheimer's Disease addresses one of the more currently unresolved aspects confounding Alzheimer's research, the significance of intraneuronal amyloid. It seeks to explain some of the unresolved questions concerning intracellular amyloid and its origin, entry, and toxicity. Following up on Dr. D'Andrea's first book, Bursting Neurons and Fading Memories: An Alternative Hypothesis for the Pathogenesis of Alzheimer's Disease, this book further examines the Inside-Out or Bursting alternative hypothesis of how amyloid escapes the circulatory system to ultimately enter neurons, also examining whether there is a relationship between intracellular amyloid, amyloid plaques, and cognitive impairment. Through a comprehensive explanation of the currently relevant scientific research on intracellular amyloid compiled in this handy reference, readers will better understand the mechanisms that lead to neuron death.
Publisher: Academic Press
ISBN: 9780128042564
Category : Science
Languages : en
Pages : 0
Book Description
Consequences of Intracellular Amyloid in Alzheimer's Disease addresses one of the more currently unresolved aspects confounding Alzheimer's research, the significance of intraneuronal amyloid. It seeks to explain some of the unresolved questions concerning intracellular amyloid and its origin, entry, and toxicity. Following up on Dr. D'Andrea's first book, Bursting Neurons and Fading Memories: An Alternative Hypothesis for the Pathogenesis of Alzheimer's Disease, this book further examines the Inside-Out or Bursting alternative hypothesis of how amyloid escapes the circulatory system to ultimately enter neurons, also examining whether there is a relationship between intracellular amyloid, amyloid plaques, and cognitive impairment. Through a comprehensive explanation of the currently relevant scientific research on intracellular amyloid compiled in this handy reference, readers will better understand the mechanisms that lead to neuron death.
Advances in Natural Computation
Author: Licheng Jiao
Publisher: Springer
ISBN: 3540459022
Category : Computers
Languages : en
Pages : 1030
Book Description
This is volume I of the proceedings of the Second International Conference on Natural Computation, ICNC 2006. After a demanding review process 168 carefully revised full papers and 86 revised short papers were selected from 1915 submissions for presentation in two volumes. This first volume includes 130 papers related to artificial neural networks, natural neural systems and cognitive science, neural network applications, as well as evolutionary computation: theory and algorithms.
Publisher: Springer
ISBN: 3540459022
Category : Computers
Languages : en
Pages : 1030
Book Description
This is volume I of the proceedings of the Second International Conference on Natural Computation, ICNC 2006. After a demanding review process 168 carefully revised full papers and 86 revised short papers were selected from 1915 submissions for presentation in two volumes. This first volume includes 130 papers related to artificial neural networks, natural neural systems and cognitive science, neural network applications, as well as evolutionary computation: theory and algorithms.
Biological and Artificial Intelligence Environments
Author: Bruno Apolloni
Publisher: Springer Science & Business Media
ISBN: 1402034326
Category : Computers
Languages : en
Pages : 389
Book Description
The book reports the proceedings of the 15th Italian workshop on neural networks issued by the Italian Society on Neural Networks SIREN. The longevity recipe of this conference stands in three main points that normally renders the reading of these proceedings so interesting as appealing. 1. The topics of the neural networks is considered an attraction pole for a set of researches centered on the inherent paradigm of the neural networks, rather than on a specific tool exclusively. Thus, the subsymbolic management of the data information content constitutes the key feature of papers in various fields such as Pattern Recognition, Stochastic Optimization, Learning, Granular Computing, and so on, with a special bias toward bioinformatics operational applications. An excerpt of all these matters may be found in the book. 2. Though managed at domestic level, the conference attracts contributions from foreign researchers as well, so that in the book the reader may capture the flavor of the state of the art in the international community. 3. The conference is a meeting of friends as well. Thus the papers generally reflect a relaxed atmosphere where researchers meet to generously exchange their thought and explain their actual results in view of a common cultural growing of the community.
Publisher: Springer Science & Business Media
ISBN: 1402034326
Category : Computers
Languages : en
Pages : 389
Book Description
The book reports the proceedings of the 15th Italian workshop on neural networks issued by the Italian Society on Neural Networks SIREN. The longevity recipe of this conference stands in three main points that normally renders the reading of these proceedings so interesting as appealing. 1. The topics of the neural networks is considered an attraction pole for a set of researches centered on the inherent paradigm of the neural networks, rather than on a specific tool exclusively. Thus, the subsymbolic management of the data information content constitutes the key feature of papers in various fields such as Pattern Recognition, Stochastic Optimization, Learning, Granular Computing, and so on, with a special bias toward bioinformatics operational applications. An excerpt of all these matters may be found in the book. 2. Though managed at domestic level, the conference attracts contributions from foreign researchers as well, so that in the book the reader may capture the flavor of the state of the art in the international community. 3. The conference is a meeting of friends as well. Thus the papers generally reflect a relaxed atmosphere where researchers meet to generously exchange their thought and explain their actual results in view of a common cultural growing of the community.
Corticonics
Author: M. Abeles
Publisher: Cambridge University Press
ISBN: 9780521376174
Category : Medical
Languages : en
Pages : 298
Book Description
Understanding how the brain works is probably the greatest scientific and intellectual challenge of our generation. The cerebral cortex is the instrument by which we carry the most complex mental functions. Fortunately, there exists an immense body of knowledge concerning both cortical structure and the properties of single neurons in the cortex. With the advent of the supercomputer, there has been increased interest in neural network modeling. What is needed is a new approach to an understanding of the mammalian cerebral cortex that will provide a link between the physiological description and the computer model. This book meets that need by combining anatomy, physiology, and modeling to achieve a quantitative description of cortical function. The material is presented didactically, starting with descriptive anatomy and comprehensively examining all aspects of modeling. The book gradually leads the reader from the macroscopic cortical anatomy and standard electrophysiological properties of single neurons to neural network models and synfire chains. The most modern trends in neural network modeling are explored.
Publisher: Cambridge University Press
ISBN: 9780521376174
Category : Medical
Languages : en
Pages : 298
Book Description
Understanding how the brain works is probably the greatest scientific and intellectual challenge of our generation. The cerebral cortex is the instrument by which we carry the most complex mental functions. Fortunately, there exists an immense body of knowledge concerning both cortical structure and the properties of single neurons in the cortex. With the advent of the supercomputer, there has been increased interest in neural network modeling. What is needed is a new approach to an understanding of the mammalian cerebral cortex that will provide a link between the physiological description and the computer model. This book meets that need by combining anatomy, physiology, and modeling to achieve a quantitative description of cortical function. The material is presented didactically, starting with descriptive anatomy and comprehensively examining all aspects of modeling. The book gradually leads the reader from the macroscopic cortical anatomy and standard electrophysiological properties of single neurons to neural network models and synfire chains. The most modern trends in neural network modeling are explored.
Subcritical Brain, The: A Synergy Of Segregated Neural Circuits In Memory, Cognition And Sensorimotor Control
Author: Yoram Baram
Publisher: World Scientific
ISBN: 981123311X
Category : Computers
Languages : en
Pages : 298
Book Description
Have over a hundred years of brain research revealed all its secrets? This book is motivated by a realization that cortical structure and behavior can be explained by a synergy of seemingly different mathematical notions: global attractors, which define non-invertible neural firing rate dynamics, random graphs, which define connectivity of neural circuit, and prime numbers, which define the dimension and category of cortical operation. Quantum computation is shown to ratify the main conclusion of the book: loosely connected small neural circuits facilitate higher information storage and processing capacities than highly connected large circuits. While these essentially separate mathematical notions have not been commonly involved in the evolution of neuroscience, they are shown in this book to be strongly inter-related in the cortical arena. Furthermore, neurophysiological experiments, as well as observations of natural behavior and evidence found in medical testing of neurologically impaired patients, are shown to support, and to be supported by the mathematical findings.Related Link(s)
Publisher: World Scientific
ISBN: 981123311X
Category : Computers
Languages : en
Pages : 298
Book Description
Have over a hundred years of brain research revealed all its secrets? This book is motivated by a realization that cortical structure and behavior can be explained by a synergy of seemingly different mathematical notions: global attractors, which define non-invertible neural firing rate dynamics, random graphs, which define connectivity of neural circuit, and prime numbers, which define the dimension and category of cortical operation. Quantum computation is shown to ratify the main conclusion of the book: loosely connected small neural circuits facilitate higher information storage and processing capacities than highly connected large circuits. While these essentially separate mathematical notions have not been commonly involved in the evolution of neuroscience, they are shown in this book to be strongly inter-related in the cortical arena. Furthermore, neurophysiological experiments, as well as observations of natural behavior and evidence found in medical testing of neurologically impaired patients, are shown to support, and to be supported by the mathematical findings.Related Link(s)