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Aging and Health - A Systems Biology Perspective
Aging is a major risk factor for chronic diseases, which in turn can provide information about the aging of a biological system. This publication serves as an introduction to systems biology and its application to biological aging. Key pathways and processes that impinge on aging are reviewed, and how they contribute to health and disease during aging is discussed. The evolution of this situation is analyzed, and the consequences for the study of genetic effects on aging are presented. Epigenetic programming of aging, as a continuation of development, creates an interface between the genome and the environment. New research into the gut microbiome describes how this interface may operate in practice with marked consequences for a variety of disorders. This analysis is bolstered by a view of the aging organism as a whole, with conclusions about the mechanisms underlying resilience of the organism to change, and is expanded with a discussion of circadian rhythms in aging. Finally, the book presents an outlook for the development of interventions to delay or to reverse the features of aging. The publication is recommended to students, researchers as well as professionals dealing with public health and public policy related to an aging society.
- Cover Page
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Front Matter
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Interdisciplinary Topics in Gerontology
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Title Page
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Copyright
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Contents
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Introduction
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References
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Introduction to the Theory of Aging Networks
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Abstract
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In the Beginning: Reductionism
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Is a System Complicated or Is It Complex?
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The Emergence of Systems Biology
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Networks and Graphs
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From Data to Graphs
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Robustness, Resilience and Frailty
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Conclusion
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Closing Thoughts
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Future Directions
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Acknowledgements
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References
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Applications to Aging Networks
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Abstract
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Networks and Graphs
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Creating a Longevity Network: An Example with Yeast
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Analyzing the Network: An Example with Yeast and Caenorhabditis elegans
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Power Plots and Scale-Free Networks
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Categorizing Small-World Networks
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Node-Node Connectivities
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Interpreting the Results
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Software for Network Analysis
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Future Directions
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Closing Thoughts
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Acknowledgements
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References
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Computational Systems Biology for Aging Research
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Abstract
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Rationale for Using Systems Modelling for Aging Research
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Advantages over and Interactions with Conventional Techniques
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Computational Systems Modelling Approaches for Aging Research
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Ordinary Differential Equations and Partial Differential Equations
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Stochastic Reaction Networks and Probability-Based Models
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Petri Net Models, Boolean Networks and Agent-Based Models
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Model Building
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Step 1: Selecting a System to Model, and Step 2: Checking for Previous Models
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Step 3: Network Diagram Construction, and Step 4: Deciding on a Mathematical Framework
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Step 5: Identify a Suitable Modelling Tool, and Step 6: Setting the Initial Conditions/ Parameters
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Step 7: Model Simulation, and Step 8: Model Validation/Parameter Inference
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Step 9: Hypothesis Examination, and Step 10: Further Wet Lab Experimentation
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Computational Systems Models of Aging - From Cell to Whole Body
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Conclusions
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References
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How Does the Body Know How Old It Is? Introducing the Epigenetic Clock Hypothesis
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Abstract
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Reasons to Believe in an Aging Clock
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Modulation of the Aging Clock Suggests a Demographic Purpose
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Aging Clocks
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Cellular Senescence and the Telomere Clock
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Other Known Biological Clocks
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Epigenetic Clock Hypothesis
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Testing the Hypothesis: Medical Implications
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Footnote
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References
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The Great Evolutionary Divide: Two Genomic Systems Biologies of Aging
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Abstract
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Rarely Sexual Evolutionary Genetics: Theoretical Expectations for Aging Genomics
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Rarely Sexual Evolutionary Genetics: Implications for the Systems Biology of Aging
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Evolutionary Genetics of Outcrossing Mendelian Populations: General Genomic Findings
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Evolutionary Genetics of Outcrossing Mendelian Populations: Implications for Their Systems Biology of Aging
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The Two Kinds of Evolutionary Genomics and the Systems Biology of Aging
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Systems Biology of Aging in Largely Asexual or Inbred Populations
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Systems Biology of Aging in Outcrossing Mendelian Populations
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Application to the Systems Biology of Aging in Humans
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Acknowledgements
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References
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Development and Aging: Two Opposite but Complementary Phenomena
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Abstract
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A Brief View of the Two Sides of Life
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Common Mechanisms between Development and Aging Outcomes
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The Essential Understanding of Topological Parameters
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Decoding the Networks: New Insights into DevAge and Its Relationship to Inflammation
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Decoding the Networks: DevAge and Its Relation to Epigenetics
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Decoding the Networks: Glucose Metabolism and Developmental Changes
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Summary of the Observed Mechanisms and Further Considerations
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References
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Aging as a Process of Deficit Accumulation: Its Utility and Origin
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Abstract
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The Accumulation of Deficits as a Proxy Measure of Aging
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Individual Frailty Trajectories: Stochastic Patterns
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Health Changes in the Fittest (The Zero State of Frailty)
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The Origin of Deficit Accumulation - A Stochastic Framework
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Queuing Theory and Little's Law
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Age-Related Deficit Accumulation Reflects the Increase of Age-Related Time of Recovery
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Changes in the Distribution of the Number of Deficits Indicates Change in Recovery Potential
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Estimating Biological Age
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Aging, Health, Wealth and Life Expectancy Worldwide
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Conclusions and Perspectives
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References
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Low-Grade Systemic Inflammation Connects Aging, Metabolic Syndrome and Cardiovascular Disease
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Abstract
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Aging, Diseases and the Regulation of Energy Allocation
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Aging and the Immune System
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Inflammation in Obesity and Metabolic Syndrome during Aging
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The Immune System and Type 2 Diabetes
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The Liver and Inflammation in Metabolic Syndrome
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Inflammatory Function, Atherosclerosis and Other Cardiovascular Consequences
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Conclusion
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References
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Modulating mTOR in Aging and Health
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Abstract
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mTOR and Aging
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mTOR Signaling
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mTOR in Nutrient and Growth Factor Sensing
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mTOR Downstream Signaling and Biological Relevance
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mTOR and Age-Related Disease
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Longevity and Health Span
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mTOR and Disease
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Systems Biology Approaches to Studying mTOR
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References
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Melatonin and Circadian Oscillators in Aging - A Dynamic Approach to the Multiply Connected Players
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Abstract
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A Systemic View on the Interconnections of Major Aging Processes
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Vicious Cycles
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Beneficial Cycles
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Pleiotropy of Melatonin in the Context of Aging
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Controversial Results at First but Not at Second Glance: The Importance of Circadian Dynamics
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Conclusion
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References
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Diet-Microbiota-Health Interactions in Older Subjects: Implications for Healthy Aging
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Abstract
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Physiological and Clinical Issues That Can Impact on the Gut Microbiota in Elderly
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Culture-Based Analyses of Intestinal Microbiota of Elderly
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The Technological Revolution
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Culture-Independent Microbiota of Older Persons
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Microbial-Based Changes in the Elderly
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Cultural Microbial Differences Observed in Different Age Groups
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Diet as a Driver of Microbiota Variation in Older People
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Factors Influencing the Gut Microbiota in Older Persons
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The Impact of Diet on Microbiota Variation
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Dietary Interventions
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Prebiotic Intervention Studies in Elderly Populations
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Prospectus, Knowledge Gaps and Required Studies
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Diet-Microbiota Interactions
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Diet-Microbiota-Medication Interactions
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Ecosystem Management, Microbiota Restoration and Replacement
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References
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Systems Biology Approaches in Aging Research
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Abstract
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The Emergence of Systems Biology ‘Flavors’
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The Conceptual Workflows of Systems Biology
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Systems Biology Comes in Several ‘Flavors’
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Why Systems Biology in Aging?
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Aging Phenotypes Are Associated with Large and Complex Networks
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Motifs of Nonlinear Dynamics in Aging Networks
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Aging as a Systemic Phenomenon
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From Understanding to Manipulation
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Aging Research Projects Using the Systems Biology Approach: The GerontoSys Initiative
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The Hematopoietic System Is an Aging Research Hub
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Histone Modifications and Stem Cell Fate
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Understanding mTOR Activation through Computational Modelling
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ROS - The Dose Makes the Poison
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Design Concept, Development and Challenges of a Systems Biology Aging Project: The Case Study of the ROSage Project
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Hypothesis, Goals and Strategy
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An Overall Perspective on the Current Biological Insights Generated in the Project
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Results Derived from the Modeling Approach Used
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Conclusions
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Acknowledgements
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References
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Conservative Growth Hormone/IGF-1 and mTOR Signaling Pathways as a Target for Aging and Cancer Prevention: Do We Really Have an Antiaging Drug?
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Abstract
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Antidiabetic Biguanides as Geroprotectors
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Effects of Rapamycin on Aging and Longevity
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Conclusion
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Acknowledgements
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References
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- Author Index
- Subject Index
- 出版地 : 德國
- 語言 : 德文
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