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Section I General Principles of Mitochondria and the Heart |
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1 Introduction to Mitochondria in the Heart |
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3 | (10) |
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The Energy-Consuming Heart |
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3 | (1) |
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The Mitochondrion: Origin, Morphology, Composition, and Dynamics |
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3 | (1) |
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Cardiac Energy Metabolism |
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4 | (2) |
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6 | (1) |
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Cardiac Mitochondria and Cell Death |
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7 | (1) |
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Mitochondria and Ca2+ Signaling: Link Between Myocardial Contraction and Cell Death |
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7 | (1) |
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Mitochondrial Dysfunction Related to Cardiovascular Disorders |
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8 | (1) |
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9 | (4) |
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2 Methods to Study Mitochondrial Structure and Function |
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13 | (16) |
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13 | (1) |
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High-Resolution Imaging of Mitochondria in Live Cells |
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13 | (1) |
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High-Resolution Electron Microscopy and Electron Tomography |
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14 | (1) |
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Molecular Biological and Biochemical Methods |
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15 | (5) |
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15 | (1) |
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In Vitro Assessment of Mitochondrial Function |
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15 | (1) |
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In Vivo Assessment of Mitochondrial Function |
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16 | (2) |
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Electrophoretic Techniques to Study Mitochondria |
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18 | (1) |
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19 | (1) |
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Transgenic Models for Assessing Mitochondrial Function in the Heart |
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20 | (1) |
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Conclusion and Future Progress |
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20 | (2) |
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22 | (1) |
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23 | (6) |
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3 Mitochondrial Structure, Composition, and Dynamics |
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29 | (30) |
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29 | (1) |
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Mitochondrial Arrangement in Cardiomyocytes |
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29 | (1) |
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Internal Structure of Mitochondria |
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30 | (10) |
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Mitochondrial Outer and Inner Membranes |
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31 | (1) |
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32 | (1) |
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Mitochondrial Permeability Transition Pore |
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33 | (1) |
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Voltage-Dependent Anion Channel |
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34 | (1) |
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Adenine Nucleotide Translocase |
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34 | (1) |
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35 | (1) |
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Mitochondrial Phosphate Carrier (PiC) |
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35 | (1) |
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36 | (1) |
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Mitochondrial Ca Channels |
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36 | (1) |
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36 | (1) |
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37 | (1) |
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38 | (1) |
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38 | (1) |
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Mitochondrial Proiein Import Channels |
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38 | (1) |
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39 | (1) |
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Presequence Translocase in the MIM (TIM23) |
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39 | (1) |
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Carrier Translocase in the MIM (TIM22) |
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40 | (1) |
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Mitochondrial Matrix and Intermemhrane Space |
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40 | (1) |
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40 | (5) |
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The Molecular Machinery and Mechanisms of Mitochondrial Fusion |
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40 | (2) |
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The Molecular Machinery and Mechanisms of Mitochondrial Fission |
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42 | (1) |
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Mitochondrial Trafficking |
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43 | (1) |
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Regulation ol Mitochondrial Dynamics |
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43 | (2) |
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45 | (1) |
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46 | (3) |
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49 | (10) |
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4 Mitochondrial Biogenesis |
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59 | (40) |
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59 | (1) |
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Mitochondrial Genome: Structure and Dynamics |
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59 | (11) |
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59 | (1) |
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60 | (2) |
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Replication of Mitochondrial DNA |
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62 | (3) |
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Transcription of Mitochondrial DNA |
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65 | (2) |
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Translation in Mitochondria |
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67 | (2) |
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69 | (1) |
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Mitochondrial Protein Biogenesis |
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70 | (5) |
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70 | (2) |
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72 | (1) |
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Redox-Regulated Import Pathway |
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73 | (1) |
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Biogenesis of the MOM Proteins |
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73 | (2) |
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Mitochondrial Lipid Biogenesis |
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75 | (2) |
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Mitochondrial Phospholipids |
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75 | (1) |
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Mitochondrial Phospholipid Biosynthesis |
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75 | (2) |
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Mitochondrial Phospholipid Traflic |
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77 | (1) |
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PGC-1α: A Central Regulator of Mitochondrial Biogenesis |
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77 | (4) |
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77 | (1) |
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78 | (1) |
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Transcriptional Regulation |
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78 | (1) |
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Posttranseriptional Regulation |
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79 | (1) |
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In Vivo Functions of PGC-1 Family Members |
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80 | (1) |
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PGC-1-Mediated Regulatory Circuitry in the Heart |
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81 | (1) |
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81 | (2) |
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83 | (3) |
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86 | (13) |
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5 Mechanisms of Bioenergy Production in Mitochondria |
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99 | (24) |
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99 | (1) |
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Pyruvate Dehydrogenase Complex |
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99 | (2) |
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Fatty Acid Oxidation (β-Oxidation Spiral) |
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101 | (3) |
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Production of Reducing Equivalents: Tricarboxylic Acid Cycle |
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104 | (4) |
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105 | (1) |
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106 | (1) |
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106 | (1) |
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2-OxogIutarate Dehydrogenase (α-Ketoglutarate Dehydrogenase) |
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106 | (1) |
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107 | (1) |
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107 | (1) |
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108 | (1) |
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Oxidative Phosphorylation |
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108 | (6) |
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NADH: Ubiquinone Oxidoreductase (Complex I) |
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108 | (1) |
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Succinate: Ubiquinone Oxidoreductase (Complex II) |
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109 | (1) |
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Ubiquinol-Cytochrome c Oxidoreductase (Complex III, or Cytochrome bc 1 Complex, or CIII) |
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110 | (1) |
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Cytochrome c Oxidase (CIV or COX) |
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111 | (1) |
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112 | (1) |
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Role of Mitochondrial Kinases in Energy and Nucleotide Homeostasis |
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112 | (1) |
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113 | (1) |
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Nucleoside Diphosphate Kinase |
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113 | (1) |
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113 | (1) |
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114 | (1) |
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115 | (1) |
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116 | (7) |
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6 Bioenergetics Interplay Between Cardiac Mitochondria and Other Subcellular Compartments |
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123 | (24) |
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123 | (14) |
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Mitochondria/Nucleus Interactions |
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123 | (4) |
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Mitochondria/Cytosol Interactions |
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127 | (4) |
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131 | (3) |
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Mitochondria and Peroxisomes Interactions |
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134 | (1) |
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134 | (3) |
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137 | (1) |
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137 | (2) |
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139 | (8) |
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Section II Heart Mitochondria Signal Transduction: Stem Cells |
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7 Endothelial Mitochondria: Contribution to Cardiovascular Function and Disease |
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147 | (10) |
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147 | (1) |
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Release of Vasodilators: Role of OXPHOS and [ Ca2+]m |
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147 | (1) |
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Role of Endothelial Mitochondria in the Generation of Reactive Oxygen Species |
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148 | (2) |
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Role of Endothelial Mitochondria in the Generation of NO |
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150 | (1) |
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Endothelial Mitochondria and Apoptosis |
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151 | (1) |
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152 | (1) |
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153 | (1) |
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153 | (4) |
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8 Heart Mitochondria: Receivers and Transmitters of Signals |
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157 | (26) |
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157 | (1) |
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157 | (2) |
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Mitochondrial Bioenergetics |
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157 | (1) |
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158 | (1) |
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Signaling at the Mitochondria |
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159 | (1) |
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Reactive Oxygen Species Generation and Signaling |
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159 | (1) |
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159 | (1) |
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Translocation of Proteins into Mitochondria |
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159 | (1) |
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Mitochondrial Retrograde Signaling |
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159 | (1) |
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Role of Calcium in Nuclear-Mitochondrial Cross Talk |
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160 | (1) |
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160 | (1) |
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Key Players in Mitochondrial Signaling |
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160 | (5) |
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160 | (1) |
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161 | (1) |
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162 | (1) |
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Mitochondrial KATP Channel |
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163 | (1) |
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Mitochondrial Permeability Transition Pore |
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164 | (1) |
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Survival and Stress Signals Impact Heart Mitochondria |
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165 | (2) |
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165 | (2) |
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167 | (1) |
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Metabolic Signals and UCPs |
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167 | (3) |
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Cardiomyopathy and Mitochondrial Signaling Defects |
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170 | (1) |
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Mitochondrial Signaling in Myocardial Ischemia and Cardioprotection |
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170 | (3) |
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Mitochondrial Signaling and Myocardial Hypertrophy |
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173 | (1) |
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Survival Signals/Apoptosis |
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174 | (1) |
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Future Prospects: Therapeutic Targets and Directions |
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174 | (1) |
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175 | (1) |
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175 | (1) |
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176 | (7) |
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9 Stem Cells and Mitochondria |
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183 | (22) |
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183 | (1) |
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Stem Cell Types and Delivery Techniques |
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183 | (4) |
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184 | (3) |
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Mechanisms of Stem Cell Sell-Renewal and Pluripotency |
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187 | (3) |
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Cell Cycle Regulation and Self-Renewal of Stem Cells |
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187 | (1) |
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Molecular Circuit of Pluripotency |
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188 | (2) |
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Mitochondrial Metabolism in Stem Cells |
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190 | (2) |
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Mitochondria Number and Morphology |
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190 | (1) |
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Mitochondrial DNA Dynamics |
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190 | (1) |
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190 | (1) |
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Oxidative Stress in Stem Cells |
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191 | (1) |
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Mitochondria-Mediated Apoptosis of Stem Cells |
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191 | (1) |
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192 | (1) |
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193 | (2) |
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195 | (10) |
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Section III Stress and Cell Death |
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10 Heart Mitochondrial ROS and Oxidative Stress |
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205 | (20) |
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205 | (1) |
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Mitochondrial ROS Production |
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205 | (2) |
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Effects of ROS on Cardiomyocytes |
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207 | (1) |
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207 | (1) |
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ROS and Cardiac Pathology |
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207 | (3) |
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Oxidative Stress in Myocardial Ischemia and HF |
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210 | (1) |
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211 | (3) |
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Oxidative Stress and Apoptosis |
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214 | (1) |
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Mitochondrial Nitric Oxide |
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214 | (1) |
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215 | (1) |
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216 | (2) |
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Conclusions and Future Directions |
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218 | (1) |
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218 | (1) |
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219 | (6) |
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11 Cell-Death Pathways and Mitochondria |
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225 | (20) |
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225 | (1) |
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225 | (5) |
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Intrinsic (Mitochondrial) Pathway |
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225 | (4) |
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229 | (1) |
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230 | (1) |
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231 | (2) |
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Cell Death in the Pathogenesis of Myocardial Disorders |
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233 | (1) |
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234 | (1) |
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235 | (2) |
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237 | (8) |
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Section IV Mitochondria in Pediatric Cardiology |
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12 Mitochondria in Pediatric Cardiovascular Diseases |
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245 | (28) |
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245 | (1) |
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General Aspects of Mitochondria |
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245 | (2) |
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Mitochondrial Cardiomyopathy |
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247 | (5) |
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Cardioneuropathies and Mitochondrial Phenotype |
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250 | (2) |
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252 | (5) |
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Clinical and Laboratory Findings in MCM |
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252 | (1) |
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Histological and Electron Microscopic (EM) Analysis |
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252 | (4) |
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Mitochondrial tRNA Mutations |
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256 | (1) |
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Mitochondrial Structural Gene Mutations |
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257 | (2) |
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257 | (1) |
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258 | (1) |
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Mutations in COX and ND Subunits |
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258 | (1) |
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258 | (1) |
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Mitochondrial Changes in Congenital Heart Defects |
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259 | (3) |
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Structural and Functional Cardiac Defects |
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259 | (1) |
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259 | (1) |
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Other Congenital Cardiomyopathies with Mitochondrial Defects |
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260 | (2) |
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Congenital Heart Defects and Mitochondrial Function |
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262 | (1) |
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Conclusions and Future Directions |
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262 | (1) |
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263 | (2) |
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265 | (8) |
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Section V The Aging Heart and Mitochondria |
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13 Mitochondria in the Aging Heart |
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273 | (22) |
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273 | (1) |
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Oxidative Stress and Aging |
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273 | (2) |
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Oxidative Damage of Mitochondrial Proteins in Aging Heart |
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275 | (1) |
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Role of Lipids in Age-Related Changes of Cardiac Mitochondria |
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275 | (3) |
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Involvement of DNA Damage in Age-Related Mitochondrial Dysfunction |
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278 | (1) |
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Loss of Cardiac Cells due (o Chronic Exposure to Free Radicals in the Senescent Myocardium |
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279 | (1) |
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Aging and Biogenesis of Mitochondria |
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280 | (1) |
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Mitochondrial Dynamics in Aging |
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281 | (1) |
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281 | (1) |
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282 | (2) |
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284 | (1) |
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284 | (2) |
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286 | (9) |
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Section VI Mitochondria in Atherosclerosis, Hypertension and Ischemia |
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14 The Role of Mitochondria in Atherosclerosis |
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295 | (10) |
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295 | (1) |
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Mitochondrial Dysfunction in Atherosclerosis |
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295 | (3) |
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295 | (2) |
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297 | (1) |
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Mitochondrial Dysfunction in Conditions Associated with Atherosclerosis |
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298 | (1) |
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298 | (1) |
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299 | (1) |
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299 | (1) |
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300 | (1) |
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301 | (4) |
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15 The Role of Mitochondria in Hypertension |
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305 | (8) |
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305 | (1) |
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Mechanisms of ROS Generation and Mitochondrial Dysfunction |
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305 | (2) |
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The Role of Mitochondrial Uncoupling Proteins |
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307 | (1) |
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The Mitochondrial DNA and Oxidative Damage |
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308 | (1) |
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Conclusions and Future Prospects |
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309 | (1) |
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309 | (1) |
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310 | (3) |
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16 Role of Mitochondria in Ischemia and Cardioprotection |
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313 | (16) |
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313 | (1) |
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Mitochondria in Ischemia and Reperfusion in the Heart |
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313 | (1) |
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Impairment of Energy Metabolism |
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313 | (1) |
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Impairment of Oxidative Metabolism |
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314 | (1) |
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Alterations in Mitochondrial Calcium Homeostasis |
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315 | (1) |
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Increased Generation of Reactive Oxygen Species |
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315 | (1) |
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Mitochondrial Permeability Transition Pore Opening |
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315 | (2) |
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ATP-Binding Cassette Mitochondrial Hrythroid |
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317 | (1) |
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Mitochondria and Cardioprotection |
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317 | (1) |
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Mitochondria Self-Defense Mechanisms |
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317 | (1) |
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Mitochondria-Directed Cardioprotection Strategies |
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318 | (2) |
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318 | (1) |
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Antioxidant and Inhibition of Monoamine Oxidase |
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319 | (1) |
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319 | (1) |
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Thioredoxin/Thioredoxin Reductase System |
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320 | (1) |
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320 | (1) |
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321 | (1) |
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322 | (7) |
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Section VII Mitochondria in Heart Failure and Dysrhythmias |
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17 Mitochondrial Dynamics in Health and Disease |
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329 | (14) |
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329 | (1) |
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Mitochondrial Dynamics in Human Pathology |
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329 | (7) |
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Autosomal Dominant Optic Atrophy |
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330 | (1) |
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Charcot-Marie-Tooth Neuropathy |
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330 | (1) |
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Charcot-Marie-Tooth Neuropathy Type 2A |
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330 | (1) |
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Charcot-Marie-Tooth Neuropathy Type 4A |
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330 | (1) |
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Abnormal Brain Development |
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330 | (1) |
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The Wolf-Hirschhorn Syndrome |
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331 | (1) |
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Obesity and Type 2 Diabetes |
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332 | (1) |
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Mitochondrial Dynamics in the Normal and Failing Heart |
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332 | (1) |
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Ischemia/Reperfusion Injury |
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333 | (1) |
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334 | (1) |
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334 | (1) |
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335 | (1) |
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336 | (1) |
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336 | (3) |
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339 | (4) |
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18 Mitochondria Play an Essential Role in Heart Failure |
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343 | (28) |
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343 | (1) |
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Mitochondrial Bioenergetics in HF |
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343 | (5) |
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343 | (3) |
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Mitochondrial ROS Generation and Antioxidant Response |
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346 | (2) |
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Critical Role of Mitochondrial Bioenergetic Enzymes and ROS in Animal Models of HF |
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348 | (2) |
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Electron Transport Chain Respirasome in HF |
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350 | (4) |
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Transgenic Models in the Study of Mitochondria Alterations in Heart Failure |
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354 | (3) |
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Mitochondrial DNA and HF in Transgenic Mice |
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356 | (1) |
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Peroxisome Proliferator-Activated Receptors-γ Coactivator 1 (PGC-1α) |
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357 | (4) |
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Peroxisome Proliferator-Activated Receptors |
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359 | (2) |
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Defects in Cytosolic Proteins Can Cause HF with Mitochondrial Dysfunction |
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361 | (1) |
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Calcium Signaling and Mitochondrial Function in HF |
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361 | (1) |
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Mitochondrial Function and Apoptosis in HF |
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362 | (1) |
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Mitochondrial Dynamics Function and Dysfunction in HF |
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362 | (1) |
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Conclusions and Future Prospect |
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362 | (2) |
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364 | (2) |
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366 | (5) |
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19 Mitochondria and Cardiac Dysrhythmias |
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371 | (16) |
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371 | (1) |
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The Role of Sarcolemmal KATP Channels in Dysrhythmia |
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371 | (1) |
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372 | (2) |
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Permeability Transitional Pore |
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373 | (1) |
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The Inner Membrane Anion Channel |
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374 | (1) |
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The Mitochondrial KATP Channels |
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375 | (2) |
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The Mitochondrial Calcium Uniporter |
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376 | (1) |
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Mitochondrial Redox Status |
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377 | (1) |
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378 | (1) |
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378 | (1) |
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379 | (8) |
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Section VIII Mitochondria in Heart Metabolism |
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20 Diabetes and Cardiac Mitochondria |
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387 | (14) |
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387 | (1) |
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Diabetes-Related Alterations in the Mitochondrial Metabolic Milieu |
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387 | (3) |
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Role of Mitochondria-Derived ROS in Diabetic Myocardium |
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390 | (1) |
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391 | (1) |
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Mitochondria and Activation of Metabolic Damaging Pathways |
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391 | (2) |
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Diabetes and Cardiac Mitochondrial Calcium Handling |
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393 | (1) |
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Maternally Inherited Diabetes and Deafness |
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393 | (1) |
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393 | (2) |
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395 | (1) |
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396 | (5) |
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21 The Role of Mitochondria in the Metabolic Syndrome and Insulin Resistance |
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401 | (12) |
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401 | (1) |
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Mechanistic Development of Insulin Resistance: The Role of Mitochondria |
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401 | (2) |
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Oxidative Stress and Mitochondrial Function |
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403 | (1) |
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Insulin Resistance and Mitochondrial Biogenesis |
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|
403 | (2) |
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Aging and Mitochondrial Function |
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405 | (1) |
|
Genetic Factors and Mitochondrial Function |
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405 | (1) |
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Cardiovascular Metabolic Syndrome: Mitochondrial Bioenergetics and Biogenesis Defects |
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|
406 | (2) |
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408 | (1) |
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|
408 | (1) |
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|
409 | (4) |
|
22 Thyroid Hormone and Myocardial Mitochondria |
|
|
413 | (18) |
|
|
413 | (1) |
|
Thyroid Hormone: Mechanisms of Regulation of Cardiac Mitochondria |
|
|
413 | (6) |
|
Genomic Actions of Thyroid Hormone: Regulation of Expression of Nuclear-Encoded Mitochondrial Proteins |
|
|
413 | (2) |
|
Thyroid Hormone Regulates Expression of Mitochondria-Encoded Proteins |
|
|
415 | (1) |
|
Thyroid Hormone as a Nongenomic Regulator of Mitochondrial Protein/Enzyme Activities |
|
|
416 | (1) |
|
Thyroid Hormone and Bioenergetics: Regulation of Mitochondrial Energy Production |
|
|
416 | (3) |
|
Thyroid Hormone and Mitochondrial Biogenesis |
|
|
419 | (2) |
|
Thyroid Hormone-Dependent Myocardial Hypertrophy and Mitochondria |
|
|
421 | (1) |
|
Mitochondria Dynamics and Thyroid Hormones |
|
|
421 | (1) |
|
|
422 | (1) |
|
|
422 | (1) |
|
|
423 | (8) |
|
Section IX Mitochondrial Therapy |
|
|
|
23 Targeting the Mitochondria in Cardiovascular Diseases |
|
|
431 | (24) |
|
|
431 | (1) |
|
Treatment of Mitochondrial Respiratory and Metabolic Defects |
|
|
431 | (8) |
|
Treatment with Antioxidants |
|
|
432 | (2) |
|
Antioxidant Defense in Heart Failure/ROS Regulation of Signaling Pathways |
|
|
434 | (3) |
|
Mitochondrial-Based Therapy of FAO Disorders, Dysrhythmias, and CHF |
|
|
437 | (1) |
|
|
438 | (1) |
|
Animal Models of Mitochondrial-Based Heart Disease |
|
|
439 | (2) |
|
Mitochondrial Defects and Gene Therapy |
|
|
441 | (3) |
|
Identification of Genetic Defects |
|
|
441 | (1) |
|
|
441 | (2) |
|
Targeting the Mitochondria Using Nucleic Acids |
|
|
443 | (1) |
|
Alternative Methods to Target Mitochondria with Bioactive Compounds |
|
|
444 | (1) |
|
Stem Cells and Mitochondrial Defects |
|
|
444 | (1) |
|
Conclusions and Future Perspectives |
|
|
444 | (1) |
|
|
445 | (2) |
|
|
447 | (8) |
|
Section X Looking to the Future of Mitochondria and the Heart |
|
|
|
24 Current Progress and Future Perspectives: Toward Mitochondrial Medicine |
|
|
455 | (20) |
|
|
455 | (1) |
|
|
455 | (2) |
|
|
457 | (1) |
|
Defects in mtDNA Dynamics |
|
|
457 | (1) |
|
Delects in mtDNA Translation |
|
|
457 | (1) |
|
Delects in OXPHOS Complexes |
|
|
457 | (1) |
|
Defects in Mitochondrial Dynamics |
|
|
458 | (1) |
|
Defects in Other Nuclear Genes Controlling Mitochondrial Functions |
|
|
458 | (1) |
|
Models for Mitochondrial Disorders |
|
|
458 | (3) |
|
|
458 | (1) |
|
Cytoplasmic Hybrid (Cybrid) Models |
|
|
458 | (1) |
|
|
459 | (1) |
|
|
459 | (1) |
|
Mouse Models with Targeted Nuclear Mitochondrial Genes |
|
|
460 | (1) |
|
Diagnosis of Mitochondrial Disorders |
|
|
461 | (4) |
|
Histological and Biochemical Screening |
|
|
461 | (1) |
|
Molecular Genetic Screening |
|
|
461 | (2) |
|
Next-Generation Sequencing |
|
|
463 | (1) |
|
Mitochondrial Gene Profiling: Microarray Technologies |
|
|
463 | (1) |
|
|
464 | (1) |
|
Conclusions and Future Trends |
|
|
465 | (1) |
|
|
465 | (3) |
|
|
468 | (7) |
Glossary |
|
475 | (10) |
Index |
|
485 | |