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ORIGINAL FIGURE IMPROVED FIGURE Cytokines/ chemokines MMPs plaque rupture disease progression inflammation Mono chemotaxis adhesion activation differentiation platelet chemokine release adhesion activation endothelium axis mot che NFkB adhesion receptors platelet-bound chemokines chemokine deposition ORIGINAL FIGURE IMPROVED FIGURE A B C D 50.00 Release Profile - 44mg vs 21mg 45.00 40.00 35.00 30.00 25.00 20.00 15.00 10.00 5.00 0.00 0.00 5.00 Silicone Reservoir Matrix 10.00 15.00 Time (Days) 20.00 25.00 30.00 ORIGINAL FIGURE IMPROVED FIGURE (a) (b) 6 1 26 5 27 5 50 52 8 53 8 59 58 56 55 54 51 60 7 4 ORIGINAL FIGURE IMPROVED FIGURE N2 N3 C9 N8 N4 N7 N6 C19 b a C18 C8 N1 C2 C1 C5 C17 C12 C11 C6 C12 C11 C16 C7 C2 C4 N5 C1 C7 C6 04 03 02 01 C3 C5 C10 C8 C14 C13 C15 C9 C3 C4 Cl2 C14 Cl1 Cl3 c 0 c ORIGINAL FIGURE IMPROVED FIGURE nt W LRP Fr izz led Delta-like/Jagged Notch b-catenin g-secretase NSCs differentiation NICD BMPR1B b-catenin Hes/Herp TCF MAML NICD CBF1 Sm o BMPR1A Gli Transcription Ptc SMAD CBP Proliferation Shh Bmil Ink4a p16 p53 Cell cycle SMAD Proliferation STAT differentiation p19Arf Rb Proliferation BMP BMP ORIGINAL FIGURE IMPROVED FIGURE Neuron Chemical toxin (i.e., paraquat/rotenone) complex I inhibition Mitochondria a-syn protofibrils Infectious Agent (i.e., influenza A virus) ? Mitochondrial disruption and/or ER stress Environmental Insult ER NH2 ROS generation Release of pro-apoptotic factors Protein misfolding COOH Calpain Cleavage ? alpha-synuclein NH2 a-syn oligomers COOH Nucleus Failed Aggresome? Protective? Lewy Body a-syn Aggregates Cell membrane Proteosome inhibition Autophagy disruption Cell death
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