c2830378c8bc9ae8520e816aa655ab5d 270644.pdf a210145fc7321e6dce17e830036ef89e59b3b005 270644.pdf 5c6a95947b367089524496463fb31049e8aad33d2b1497970cdb6404fee7aa7c 270644.pdf Title: MCL-1 Inhibition Overcomes Anti-apoptotic Adaptation to Targeted Therapies in B-Cell Precursor Acute Lymphoblastic Leukemia Subject: Multiple targeted therapies are currently explored for pediatric and young adult B-cell precursor acute lymphoblastic leukemia (BCP-ALL) treatment. Keywords: pediatric leukemia, targeted therapies, resistance, apoptosis, BH3 mimetics Author: Joan Montero Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.15 CreationDate: Thu Sep 2 09:35:18 2021 CEST ModDate: Thu Sep 2 16:28:09 2021 CEST Tagged: no UserProperties: no Suspects: no Form: AcroForm JavaScript: no Pages: 15 Encrypted: no Page size: 595.276 x 779.528 pts Page rot: 0 File size: 2252319 bytes Optimized: no PDF version: 1.6 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- LXIVPA+MinionPro-Regular Type 1 Custom yes yes no 24 0 RKPXGG+HelveticaNeueLTStd-Bd Type 1 Custom yes yes no 25 0 XTGFFE+HelveticaNeueLTStd-Lt Type 1 Custom yes yes no 26 0 CCVXXJ+HelveticaNeueLTStd-BdIt Type 1 Custom yes yes no 31 0 ZBYBIR+HelveticaNeueLTStd-LtIt Type 1 Custom yes yes no 32 0 SADBPL+HelveticaNeueLTStd-MdIt Type 1 Custom yes yes no 33 0 RITMDE+MTSYN Type 1 Builtin yes yes no 128 0 VXWSEY+RBLMI Type 1 Builtin yes yes no 195 0 NFNYPK+MinionPro-It Type 1 Custom yes yes no 199 0 JYDOCF+MTGU Type 1 Builtin yes yes no 194 0 WJQTMP+MinionPro-Bold Type 1 Custom yes yes no 269 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-05-27 03:07:39 CEST RepresentationInformation: 270644.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-05-26 16:25:05 CEST Size: 2252319 Format: PDF Version: 1.6 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 0 FreeObjects: 9 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseOutlines Outlines: Item: Title: MCL-1 Inhibition Overcomes Anti-apoptotic Adaptation to Targeted Therapies in B-Cell Precursor Acute Lymphoblastic Leukemia Children: Item: Title: Introduction Item: Title: Materials and Methods Children: Item: Title: Cell Lines and Treatments Item: Title: Cell Death Assay Item: Title: Dynamic BH3 Profiling Item: Title: Protein Extraction Item: Title: Immunoprecipitations Item: Title: Immunoblotting Item: Title: Precursor BCP-ALL PDX Model Generation Item: Title: DBP With PDX Cells Item: Title: Statistical Analysis Item: Title: Results Children: Item: Title: DBP Predicts Cytotoxicity in BCP-ALL Cell Lines Item: Title: Trametinib Induces MCL-1 Dependence in NALM-6 Cell Line Item: Title: Combination of Low-Dose Sunitinib and BH3 Mimetics Synergize to Maintain Treatment Efficacy Item: Title: Pediatric BCP-ALL PDX Recapitulates SEM Anti-apoptotic Adaptation Item: Title: Discussion Item: Title: Data Availability Statement Item: Title: Ethics Statement Item: Title: Author Contributions Item: Title: Funding Item: Title: Acknowledgments Item: Title: Supplementary Material Item: Title: References Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: ZBYBIR+HelveticaNeueLTStd-LtIt FontSubset: true FirstChar: 39 LastChar: 250 FontDescriptor: FontName: ZBYBIR+HelveticaNeueLTStd-LtIt Flags: Symbolic FontBBox: -165, -214, 1099, 951 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: RITMDE+MTSYN FontSubset: true FirstChar: 0 LastChar: 67 FontDescriptor: FontName: RITMDE+MTSYN Flags: Symbolic FontBBox: 0, -954, 1043, 900 FontFile: true Font: BaseFont: SADBPL+HelveticaNeueLTStd-MdIt FontSubset: true FirstChar: 42 LastChar: 252 FontDescriptor: FontName: SADBPL+HelveticaNeueLTStd-MdIt Flags: Symbolic FontBBox: -165, -218, 1125, 947 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: JYDOCF+MTGU FontSubset: true FirstChar: 109 LastChar: 109 FontDescriptor: FontName: JYDOCF+MTGU Flags: Symbolic FontBBox: 25, -213, 839, 683 FontFile: true Font: BaseFont: VXWSEY+RBLMI FontSubset: true FirstChar: 49 LastChar: 62 FontDescriptor: FontName: VXWSEY+RBLMI Flags: Symbolic FontBBox: -11, -230, 987, 750 FontFile: true Font: BaseFont: NFNYPK+MinionPro-It FontSubset: true FirstChar: 19 LastChar: 241 FontDescriptor: FontName: NFNYPK+MinionPro-It Flags: Symbolic FontBBox: -201, -360, 1684, 919 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: LXIVPA+MinionPro-Regular FontSubset: true FirstChar: 2 LastChar: 252 FontDescriptor: FontName: LXIVPA+MinionPro-Regular Flags: Symbolic FontBBox: -289, -360, 1684, 917 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: RKPXGG+HelveticaNeueLTStd-Bd FontSubset: true FirstChar: 2 LastChar: 124 FontDescriptor: FontName: RKPXGG+HelveticaNeueLTStd-Bd Flags: Symbolic FontBBox: -166, -218, 1078, 975 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: XTGFFE+HelveticaNeueLTStd-Lt FontSubset: true FirstChar: 2 LastChar: 241 FontDescriptor: FontName: XTGFFE+HelveticaNeueLTStd-Lt Flags: Symbolic FontBBox: -166, -214, 1050, 967 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: WJQTMP+MinionPro-Bold FontSubset: true FirstChar: 3 LastChar: 121 FontDescriptor: FontName: WJQTMP+MinionPro-Bold Flags: Symbolic FontBBox: -318, -360, 1684, 917 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: CCVXXJ+HelveticaNeueLTStd-BdIt FontSubset: true FirstChar: 42 LastChar: 121 FontDescriptor: FontName: CCVXXJ+HelveticaNeueLTStd-BdIt Flags: Symbolic FontBBox: -166, -218, 1129, 975 FontFile: true EncodingDictionary: Differences: true XMP: pediatric leukemia, targeted therapies, resistance, apoptosis, BH3 mimetics pdfTeX-1.40.15 1.5 application/pdf fcell-09-695225.tex MCL-1 Inhibition Overcomes Anti-apoptotic Adaptation to Targeted Therapies in B-Cell Precursor Acute Lymphoblastic Leukemia Multiple targeted therapies are currently explored for pediatric and young adult B-cell precursor acute lymphoblastic leukemia (BCP-ALL) treatment. Joan Montero pediatric leukemia targeted therapies resistance apoptosis BH3 mimetics 2021-09-02T13:05:18+05:30 2021-09-02T13:05:18+05:30 2021-09-02T19:58:09+05:30 2021-09-02T19:58:09+05:30 LaTeX with hyperref package uuid:005f7f26-2bbb-467a-be4c-e46cea339b62 uuid:99bc072a-dfff-4688-aac5-d4211bbddec3 Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Rect: 43, 718, 270, 754 Annotation: Subtype: Link Rect: 474, 736, 551, 745 Annotation: Subtype: Link Rect: 455, 727, 551, 737 Annotation: Subtype: Link Rect: 454, 718, 551, 729 Annotation: Subtype: Link Rect: 86, 432, 160, 442 Annotation: Subtype: Link Rect: 76, 67, 160, 74 Annotation: Subtype: Link Rect: 521, 677, 551, 707 Annotation: Subtype: Link Rect: 176, 534, 551, 648 Annotation: Subtype: Link Rect: 43, 29, 176, 38 Annotation: Subtype: Link Rect: 179, 29, 239, 38 Annotation: Subtype: Link Rect: 415, 29, 551, 38 Page: Sequence: 2 Annotations: Annotation: Subtype: Link Rect: 168, 660, 233, 671 ActionDest: 710 Annotation: Subtype: Link Rect: 239, 660, 259, 671 ActionDest: 710 Annotation: Subtype: Link Rect: 196, 637, 290, 648 ActionDest: 759 Annotation: Subtype: Link Rect: 43, 626, 64, 637 ActionDest: 759 Annotation: Subtype: Link Rect: 181, 580, 292, 591 ActionDest: 759 Annotation: Subtype: Link Rect: 43, 568, 108, 580 ActionDest: 759 Annotation: Subtype: Link Rect: 115, 568, 135, 580 ActionDest: 759 Annotation: Subtype: Link Rect: 235, 557, 290, 568 ActionDest: 710 Annotation: Subtype: Link Rect: 43, 545, 64, 557 ActionDest: 710 Annotation: Subtype: Link Rect: 234, 545, 290, 557 ActionDest: 759 Annotation: Subtype: Link Rect: 43, 534, 64, 545 ActionDest: 759 Annotation: Subtype: Link Rect: 156, 488, 219, 500 ActionDest: 759 Annotation: Subtype: Link Rect: 222, 488, 242, 500 ActionDest: 759 Annotation: Subtype: Link Rect: 126, 454, 170, 465 ActionDest: 710 Annotation: Subtype: Link Rect: 173, 454, 193, 465 ActionDest: 710 Annotation: Subtype: Link Rect: 183, 374, 208, 385 ActionDest: 710 Annotation: Subtype: Link Rect: 213, 374, 233, 385 ActionDest: 710 Annotation: Subtype: Link Rect: 170, 328, 210, 339 ActionDest: 648 Annotation: Subtype: Link Rect: 213, 328, 233, 339 ActionDest: 648 Annotation: Subtype: Link Rect: 264, 271, 292, 282 ActionDest: 648 Annotation: Subtype: Link Rect: 43, 259, 64, 270 ActionDest: 648 Annotation: Subtype: Link Rect: 67, 259, 87, 270 ActionDest: 648 Annotation: Subtype: Link Rect: 90, 259, 132, 270 ActionDest: 710 Annotation: Subtype: Link Rect: 135, 259, 155, 270 ActionDest: 710 Annotation: Subtype: Link Rect: 212, 203, 262, 213 ActionDest: 710 Annotation: Subtype: Link Rect: 264, 203, 284, 213 ActionDest: 710 Annotation: Subtype: Link Rect: 241, 145, 292, 156 ActionDest: 710 Annotation: Subtype: Link Rect: 43, 133, 70, 144 ActionDest: 710 Annotation: Subtype: Link Rect: 74, 133, 94, 144 ActionDest: 710 Annotation: Subtype: Link Rect: 261, 122, 292, 133 ActionDest: 710 Annotation: Subtype: Link Rect: 43, 110, 91, 121 ActionDest: 710 Annotation: Subtype: Link Rect: 96, 110, 116, 121 ActionDest: 710 Annotation: Subtype: Link Rect: 119, 87, 172, 99 ActionDest: 710 Annotation: Subtype: Link Rect: 175, 87, 195, 99 ActionDest: 710 Annotation: Subtype: Link Rect: 353, 706, 403, 717 ActionDest: 759 Annotation: Subtype: Link Rect: 406, 706, 427, 717 ActionDest: 759 Annotation: Subtype: Link Rect: 355, 672, 409, 683 ActionDest: 710 Annotation: Subtype: Link Rect: 412, 672, 432, 683 ActionDest: 710 Annotation: Subtype: Link Rect: 380, 637, 434, 648 ActionDest: 710 Annotation: Subtype: Link Rect: 440, 637, 460, 648 ActionDest: 710 Annotation: Subtype: Link Rect: 491, 626, 549, 637 ActionDest: 710 Annotation: Subtype: Link Rect: 302, 614, 322, 626 ActionDest: 710 Annotation: Subtype: Link Rect: 339, 523, 383, 534 ActionDest: 759 Annotation: Subtype: Link Rect: 388, 523, 408, 534 ActionDest: 759 Annotation: Subtype: Link Rect: 305, 511, 326, 522 ActionDest: 710 Annotation: Subtype: Link Rect: 330, 511, 350, 522 ActionDest: 710 Annotation: Subtype: Link Rect: 396, 375, 436, 385 ActionDest: 710 Annotation: Subtype: Link Rect: 439, 375, 459, 385 ActionDest: 710 Annotation: Subtype: Link Rect: 470, 282, 526, 293 ActionDest: 710 Annotation: Subtype: Link Rect: 528, 282, 549, 293 ActionDest: 710 Annotation: Subtype: Link Rect: 302, 270, 322, 282 ActionDest: 710 Annotation: Subtype: Link Rect: 326, 270, 346, 282 ActionDest: 710 Annotation: Subtype: Link Rect: 349, 270, 387, 282 ActionDest: 759 Annotation: Subtype: Link Rect: 390, 270, 411, 282 ActionDest: 759 Annotation: Subtype: Link Rect: 414, 270, 478, 282 ActionDest: 759 Annotation: Subtype: Link Rect: 481, 270, 501, 282 ActionDest: 759 Annotation: Subtype: Link Rect: 504, 270, 549, 282 ActionDest: 648 Annotation: Subtype: Link Rect: 302, 259, 322, 270 ActionDest: 648 Annotation: Subtype: Link Rect: 326, 259, 374, 270 ActionDest: 648 Annotation: Subtype: Link Rect: 378, 259, 398, 270 ActionDest: 648 Annotation: Subtype: Link Rect: 338, 225, 390, 236 ActionDest: 710 Annotation: Subtype: Link Rect: 393, 225, 413, 236 ActionDest: 710 Annotation: Subtype: Link Rect: 416, 225, 491, 236 ActionDest: 710 Annotation: Subtype: Link Rect: 495, 225, 515, 236 ActionDest: 710 Annotation: Subtype: Link Rect: 365, 179, 413, 190 ActionDest: 648 Annotation: Subtype: Link Rect: 415, 179, 435, 190 ActionDest: 648 Annotation: Subtype: Link Rect: 492, 133, 551, 144 ActionDest: 759 Annotation: Subtype: Link Rect: 302, 122, 322, 133 ActionDest: 759 Annotation: Subtype: Link Rect: 324, 122, 345, 133 ActionDest: 759 Annotation: Subtype: Link Rect: 347, 122, 401, 133 ActionDest: 710 Annotation: Subtype: Link Rect: 404, 122, 424, 133 ActionDest: 710 Annotation: Subtype: Link Rect: 426, 122, 471, 133 ActionDest: 710 Annotation: Subtype: Link Rect: 473, 122, 493, 133 ActionDest: 710 Annotation: Subtype: Link Rect: 496, 122, 549, 133 ActionDest: 759 Annotation: Subtype: Link Rect: 302, 110, 322, 121 ActionDest: 759 Annotation: Subtype: Link Rect: 43, 29, 176, 38 Annotation: Subtype: Link Rect: 179, 29, 239, 38 Annotation: Subtype: Link Rect: 415, 29, 551, 38 Page: Sequence: 3 Annotations: Annotation: Subtype: Link Rect: 89, 213, 139, 224 ActionDest: 759 Annotation: Subtype: Link Rect: 145, 213, 165, 224 ActionDest: 759 Annotation: Subtype: Link Rect: 171, 213, 235, 224 ActionDest: 710 Annotation: Subtype: Link Rect: 241, 213, 261, 224 ActionDest: 710 Annotation: Subtype: Link Rect: 267, 213, 292, 224 ActionDest: 648 Annotation: Subtype: Link Rect: 43, 201, 67, 213 ActionDest: 648 Annotation: Subtype: Link Rect: 73, 201, 93, 213 ActionDest: 648 Annotation: Subtype: Link Rect: 43, 29, 176, 38 Annotation: Subtype: Link Rect: 179, 29, 239, 38 Annotation: Subtype: Link Rect: 415, 29, 551, 38 Page: Sequence: 4 Annotations: Annotation: Subtype: Link Rect: 127, 364, 177, 376 ActionDest: 710 Annotation: Subtype: Link Rect: 181, 364, 202, 376 ActionDest: 710 Annotation: Subtype: Link Rect: 206, 364, 262, 376 ActionDest: 759 Annotation: Subtype: Link Rect: 267, 364, 287, 376 ActionDest: 759 Annotation: Subtype: Link Rect: 146, 133, 230, 144 ActionDest: 710 Annotation: Subtype: Link Rect: 233, 133, 253, 144 ActionDest: 710 Annotation: Subtype: Link Rect: 500, 620, 549, 632 ActionDest: 710 Annotation: Subtype: Link Rect: 302, 609, 322, 620 ActionDest: 710 Annotation: Subtype: Link Rect: 382, 598, 432, 609 ActionDest: 648 Annotation: Subtype: Link Rect: 436, 598, 456, 609 ActionDest: 648 Annotation: Subtype: Link Rect: 305, 574, 349, 586 ActionDest: 648 Annotation: Subtype: Link Rect: 352, 574, 372, 586 ActionDest: 648 Annotation: Subtype: Link Rect: 532, 574, 551, 586 ActionDest: 710 Annotation: Subtype: Link Rect: 302, 563, 323, 574 ActionDest: 710 Annotation: Subtype: Link Rect: 327, 563, 347, 574 ActionDest: 710 Annotation: Subtype: Link Rect: 503, 506, 545, 517 ActionDest: 307 Annotation: Subtype: Link Rect: 422, 437, 466, 448 ActionDest: 307 Annotation: Subtype: Link Rect: 450, 368, 493, 379 ActionDest: 307 Annotation: Subtype: Link Rect: 305, 311, 410, 322 ActionDest: 648 Annotation: Subtype: Link Rect: 435, 276, 545, 288 ActionDest: 648 Annotation: Subtype: Link Rect: 305, 133, 352, 144 ActionDest: 759 Annotation: Subtype: Link Rect: 357, 133, 378, 144 ActionDest: 759 Annotation: Subtype: Link Rect: 383, 133, 448, 144 ActionDest: 710 Annotation: Subtype: Link Rect: 453, 133, 473, 144 ActionDest: 710 Annotation: Subtype: Link Rect: 478, 133, 523, 144 ActionDest: 710 Annotation: Subtype: Link Rect: 528, 133, 549, 144 ActionDest: 710 Annotation: Subtype: Link Rect: 302, 122, 344, 133 ActionDest: 759 Annotation: Subtype: Link Rect: 349, 122, 369, 133 ActionDest: 759 Annotation: Subtype: Link Rect: 43, 29, 176, 38 Annotation: Subtype: Link Rect: 179, 29, 239, 38 Annotation: Subtype: Link Rect: 415, 29, 551, 38 Page: Sequence: 5 Annotations: Annotation: Subtype: Link Rect: 0, 300, 1, 312 ActionDest: 5 Annotation: Subtype: Link Rect: 0, 300, 1, 312 ActionDest: 5 Annotation: Subtype: Link Rect: 462, 283, 510, 292 Annotation: Subtype: Link Rect: 182, 110, 225, 122 ActionDest: 332 Annotation: Subtype: Link Rect: 355, 122, 396, 133 ActionDest: 332 Annotation: Subtype: Link Rect: 43, 29, 176, 38 Annotation: Subtype: Link Rect: 179, 29, 239, 38 Annotation: Subtype: Link Rect: 415, 29, 551, 38 Page: Sequence: 6 Annotations: Annotation: Subtype: Link Rect: 47, 76, 93, 87 ActionDest: 332 Annotation: Subtype: Link Rect: 373, 87, 480, 99 ActionDest: 648 Annotation: Subtype: Link Rect: 407, 76, 464, 87 ActionDest: 759 Annotation: Subtype: Link Rect: 469, 76, 489, 87 ActionDest: 759 Annotation: Subtype: Link Rect: 43, 29, 176, 38 Annotation: Subtype: Link Rect: 179, 29, 239, 38 Annotation: Subtype: Link Rect: 415, 29, 551, 38 Page: Sequence: 7 Annotations: Annotation: Subtype: Link Rect: 214, 660, 257, 671 ActionDest: 332 Annotation: Subtype: Link Rect: 47, 626, 150, 637 ActionDest: 648 Annotation: Subtype: Link Rect: 86, 580, 127, 591 ActionDest: 366 Annotation: Subtype: Link Rect: 189, 546, 231, 557 ActionDest: 366 Annotation: Subtype: Link Rect: 184, 534, 237, 545 ActionDest: 710 Annotation: Subtype: Link Rect: 239, 534, 259, 545 ActionDest: 710 Annotation: Subtype: Link Rect: 261, 534, 290, 545 ActionDest: 710 Annotation: Subtype: Link Rect: 43, 523, 64, 534 ActionDest: 710 Annotation: Subtype: Link Rect: 66, 523, 122, 534 ActionDest: 710 Annotation: Subtype: Link Rect: 124, 523, 145, 534 ActionDest: 710 Annotation: Subtype: Link Rect: 502, 706, 545, 717 ActionDest: 366 Annotation: Subtype: Link Rect: 459, 683, 500, 694 ActionDest: 332 Annotation: Subtype: Link Rect: 422, 637, 465, 648 ActionDest: 332 Annotation: Subtype: Link Rect: 447, 614, 488, 626 ActionDest: 332 Annotation: Subtype: Link Rect: 43, 29, 176, 38 Annotation: Subtype: Link Rect: 179, 29, 239, 38 Annotation: Subtype: Link Rect: 415, 29, 551, 38 Page: Sequence: 8 Annotations: Annotation: Subtype: Link Rect: 47, 707, 101, 717 ActionDest: 759 Annotation: Subtype: Link Rect: 103, 707, 123, 717 ActionDest: 759 Annotation: Subtype: Link Rect: 109, 671, 128, 683 ActionDest: 759 Annotation: Subtype: Link Rect: 132, 671, 152, 683 ActionDest: 759 Annotation: Subtype: Link Rect: 433, 683, 488, 694 ActionDest: 648 Annotation: Subtype: Link Rect: 494, 683, 514, 694 ActionDest: 648 Annotation: Subtype: Link Rect: 520, 683, 551, 694 ActionDest: 710 Annotation: Subtype: Link Rect: 302, 672, 323, 683 ActionDest: 710 Annotation: Subtype: Link Rect: 327, 672, 347, 683 ActionDest: 710 Annotation: Subtype: Link Rect: 43, 29, 176, 38 Annotation: Subtype: Link Rect: 179, 29, 239, 38 Annotation: Subtype: Link Rect: 415, 29, 551, 38 Page: Sequence: 9 Annotations: Annotation: Subtype: Link Rect: 216, 706, 258, 717 ActionDest: 307 Annotation: Subtype: Link Rect: 244, 660, 287, 671 ActionDest: 393 Annotation: Subtype: Link Rect: 47, 591, 146, 603 ActionDest: 648 Annotation: Subtype: Link Rect: 166, 580, 211, 591 ActionDest: 393 Annotation: Subtype: Link Rect: 211, 500, 252, 511 ActionDest: 393 Annotation: Subtype: Link Rect: 246, 454, 287, 465 ActionDest: 393 Annotation: Subtype: Link Rect: 246, 442, 290, 454 ActionDest: 759 Annotation: Subtype: Link Rect: 43, 431, 64, 442 ActionDest: 759 Annotation: Subtype: Link Rect: 114, 419, 223, 431 ActionDest: 648 Annotation: Subtype: Link Rect: 135, 397, 186, 408 ActionDest: 648 Annotation: Subtype: Link Rect: 189, 397, 209, 408 ActionDest: 648 Annotation: Subtype: Link Rect: 213, 397, 263, 408 ActionDest: 648 Annotation: Subtype: Link Rect: 267, 397, 287, 408 ActionDest: 648 Annotation: Subtype: Link Rect: 181, 328, 225, 339 ActionDest: 393 Annotation: Subtype: Link Rect: 230, 316, 292, 328 ActionDest: 648 Annotation: Subtype: Link Rect: 43, 305, 85, 316 ActionDest: 648 Annotation: Subtype: Link Rect: 238, 236, 279, 247 ActionDest: 527 Annotation: Subtype: Link Rect: 78, 190, 121, 202 ActionDest: 527 Annotation: Subtype: Link Rect: 119, 144, 161, 156 ActionDest: 527 Annotation: Subtype: Link Rect: 225, 64, 269, 76 ActionDest: 393 Annotation: Subtype: Link Rect: 458, 694, 503, 706 ActionDest: 572 Annotation: Subtype: Link Rect: 354, 671, 398, 683 ActionDest: 572 Annotation: Subtype: Link Rect: 400, 626, 442, 637 ActionDest: 572 Annotation: Subtype: Link Rect: 426, 473, 478, 485 ActionDest: 648 Annotation: Subtype: Link Rect: 482, 473, 503, 485 ActionDest: 648 Annotation: Subtype: Link Rect: 339, 382, 375, 393 ActionDest: 602 Annotation: Subtype: Link Rect: 341, 347, 445, 359 ActionDest: 648 Annotation: Subtype: Link Rect: 305, 324, 340, 336 ActionDest: 602 Annotation: Subtype: Link Rect: 379, 260, 442, 270 ActionDest: 710 Annotation: Subtype: Link Rect: 448, 260, 468, 270 ActionDest: 710 Annotation: Subtype: Link Rect: 475, 260, 519, 270 ActionDest: 759 Annotation: Subtype: Link Rect: 525, 260, 545, 270 ActionDest: 759 Annotation: Subtype: Link Rect: 420, 236, 481, 247 ActionDest: 648 Annotation: Subtype: Link Rect: 486, 236, 506, 247 ActionDest: 648 Annotation: Subtype: Link Rect: 511, 236, 549, 247 ActionDest: 710 Annotation: Subtype: Link Rect: 302, 225, 322, 236 ActionDest: 710 Annotation: Subtype: Link Rect: 447, 190, 520, 202 ActionDest: 759 Annotation: Subtype: Link Rect: 525, 190, 545, 202 ActionDest: 759 Annotation: Subtype: Link Rect: 362, 110, 413, 121 ActionDest: 710 Annotation: Subtype: Link Rect: 416, 110, 436, 121 ActionDest: 710 Annotation: Subtype: Link Rect: 43, 29, 176, 38 Annotation: Subtype: Link Rect: 179, 29, 239, 38 Annotation: Subtype: Link Rect: 415, 29, 551, 38 Page: Sequence: 10 Annotations: Annotation: Subtype: Link Rect: 151, 236, 239, 248 ActionDest: 710 Annotation: Subtype: Link Rect: 243, 236, 263, 248 ActionDest: 710 Annotation: Subtype: Link Rect: 47, 180, 101, 190 ActionDest: 710 Annotation: Subtype: Link Rect: 104, 180, 124, 190 ActionDest: 710 Annotation: Subtype: Link Rect: 47, 111, 105, 122 ActionDest: 710 Annotation: Subtype: Link Rect: 108, 111, 128, 122 ActionDest: 710 Annotation: Subtype: Link Rect: 132, 111, 152, 122 ActionDest: 710 Annotation: Subtype: Link Rect: 155, 111, 175, 122 ActionDest: 710 Annotation: Subtype: Link Rect: 179, 111, 243, 122 ActionDest: 759 Annotation: Subtype: Link Rect: 246, 111, 267, 122 ActionDest: 759 Annotation: Subtype: Link Rect: 270, 111, 292, 122 ActionDest: 759 Annotation: Subtype: Link Rect: 43, 99, 66, 110 ActionDest: 759 Annotation: Subtype: Link Rect: 70, 99, 90, 110 ActionDest: 759 Annotation: Subtype: Link Rect: 95, 99, 151, 110 ActionDest: 710 Annotation: Subtype: Link Rect: 156, 99, 176, 110 ActionDest: 710 Annotation: Subtype: Link Rect: 181, 99, 238, 110 ActionDest: 759 Annotation: Subtype: Link Rect: 242, 99, 263, 110 ActionDest: 759 Annotation: Subtype: Link Rect: 267, 99, 292, 110 ActionDest: 648 Annotation: Subtype: Link Rect: 43, 87, 66, 99 ActionDest: 648 Annotation: Subtype: Link Rect: 71, 87, 91, 99 ActionDest: 648 Annotation: Subtype: Link Rect: 96, 87, 119, 99 ActionDest: 710 Annotation: Subtype: Link Rect: 124, 87, 144, 99 ActionDest: 710 Annotation: Subtype: Link Rect: 525, 225, 551, 236 ActionDest: 710 Annotation: Subtype: Link Rect: 302, 214, 324, 225 ActionDest: 710 Annotation: Subtype: Link Rect: 329, 214, 349, 225 ActionDest: 710 Annotation: Subtype: Link Rect: 417, 156, 467, 167 ActionDest: 710 Annotation: Subtype: Link Rect: 471, 156, 492, 167 ActionDest: 710 Annotation: Subtype: Link Rect: 467, 145, 522, 156 ActionDest: 648 Annotation: Subtype: Link Rect: 528, 145, 549, 156 ActionDest: 648 Annotation: Subtype: Link Rect: 302, 133, 340, 144 ActionDest: 710 Annotation: Subtype: Link Rect: 344, 133, 364, 144 ActionDest: 710 Annotation: Subtype: Link Rect: 43, 29, 176, 38 Annotation: Subtype: Link Rect: 179, 29, 239, 38 Annotation: Subtype: Link Rect: 415, 29, 551, 38 Page: Sequence: 11 Annotations: Annotation: Subtype: Link Rect: 47, 271, 107, 282 ActionDest: 759 Annotation: Subtype: Link Rect: 112, 271, 132, 282 ActionDest: 759 Annotation: Subtype: Link Rect: 256, 236, 292, 248 ActionDest: 710 Annotation: Subtype: Link Rect: 43, 226, 83, 236 ActionDest: 710 Annotation: Subtype: Link Rect: 88, 226, 108, 236 ActionDest: 710 Annotation: Subtype: Link Rect: 113, 226, 192, 236 ActionDest: 759 Annotation: Subtype: Link Rect: 197, 226, 217, 236 ActionDest: 759 Annotation: Subtype: Link Rect: 222, 226, 290, 236 ActionDest: 759 Annotation: Subtype: Link Rect: 43, 214, 64, 225 ActionDest: 759 Annotation: Subtype: Link Rect: 68, 214, 107, 225 ActionDest: 710 Annotation: Subtype: Link Rect: 112, 214, 132, 225 ActionDest: 710 Annotation: Subtype: Link Rect: 116, 179, 158, 190 ActionDest: 710 Annotation: Subtype: Link Rect: 161, 179, 181, 190 ActionDest: 710 Annotation: Subtype: Link Rect: 184, 179, 225, 190 ActionDest: 710 Annotation: Subtype: Link Rect: 227, 179, 248, 190 ActionDest: 710 Annotation: Subtype: Link Rect: 120, 110, 181, 122 ActionDest: 710 Annotation: Subtype: Link Rect: 186, 110, 207, 122 ActionDest: 710 Annotation: Subtype: Link Rect: 211, 110, 262, 122 ActionDest: 648 Annotation: Subtype: Link Rect: 267, 110, 287, 122 ActionDest: 648 Annotation: Subtype: Link Rect: 499, 122, 549, 133 ActionDest: 648 Annotation: Subtype: Link Rect: 302, 110, 322, 122 ActionDest: 648 Annotation: Subtype: Link Rect: 327, 110, 367, 122 ActionDest: 759 Annotation: Subtype: Link Rect: 371, 110, 391, 122 ActionDest: 759 Annotation: Subtype: Link Rect: 395, 110, 451, 122 ActionDest: 648 Annotation: Subtype: Link Rect: 456, 110, 476, 122 ActionDest: 648 Annotation: Subtype: Link Rect: 305, 76, 348, 87 ActionDest: 759 Annotation: Subtype: Link Rect: 354, 76, 374, 87 ActionDest: 759 Annotation: Subtype: Link Rect: 380, 76, 428, 87 ActionDest: 759 Annotation: Subtype: Link Rect: 433, 76, 454, 87 ActionDest: 759 Annotation: Subtype: Link Rect: 43, 29, 176, 38 Annotation: Subtype: Link Rect: 179, 29, 239, 38 Annotation: Subtype: Link Rect: 415, 29, 551, 38 Page: Sequence: 12 Annotations: Annotation: Subtype: Link Rect: 47, 419, 92, 431 ActionDest: 710 Annotation: Subtype: Link Rect: 95, 419, 116, 431 ActionDest: 710 Annotation: Subtype: Link Rect: 47, 271, 104, 282 ActionDest: 648 Annotation: Subtype: Link Rect: 108, 271, 128, 282 ActionDest: 648 Annotation: Subtype: Link Rect: 84, 110, 135, 121 ActionDest: 710 Annotation: Subtype: Link Rect: 138, 110, 158, 121 ActionDest: 710 Annotation: Subtype: Link Rect: 574, 342, 576, 355 ActionDest: 5 Annotation: Subtype: Link Rect: 574, 265, 576, 277 ActionDest: 5 Annotation: Subtype: Link Rect: 43, 29, 176, 38 Annotation: Subtype: Link Rect: 179, 29, 239, 38 Annotation: Subtype: Link Rect: 415, 29, 551, 38 Page: Sequence: 13 Annotations: Annotation: Subtype: Link Rect: 81, 381, 292, 392 Annotation: Subtype: Link Rect: 43, 369, 186, 381 Annotation: Subtype: Link Rect: 77, 289, 180, 298 Annotation: Subtype: Link Rect: 128, 251, 228, 261 Annotation: Subtype: Link Rect: 279, 232, 293, 242 Annotation: Subtype: Link Rect: 53, 224, 140, 232 Annotation: Subtype: Link Rect: 114, 176, 228, 185 Annotation: Subtype: Link Rect: 75, 147, 165, 156 Annotation: Subtype: Link Rect: 230, 119, 293, 128 Annotation: Subtype: Link Rect: 53, 110, 98, 118 Annotation: Subtype: Link Rect: 250, 81, 293, 90 Annotation: Subtype: Link Rect: 53, 72, 103, 80 Annotation: Subtype: Link Rect: 312, 309, 381, 317 Annotation: Subtype: Link Rect: 312, 280, 428, 289 Annotation: Subtype: Link Rect: 359, 243, 434, 251 Annotation: Subtype: Link Rect: 510, 204, 551, 213 Annotation: Subtype: Link Rect: 312, 196, 381, 204 Annotation: Subtype: Link Rect: 380, 148, 475, 156 Annotation: Subtype: Link Rect: 494, 119, 551, 128 Annotation: Subtype: Link Rect: 312, 111, 328, 118 Annotation: Subtype: Link Rect: 377, 71, 460, 81 Annotation: Subtype: Link Rect: 43, 29, 176, 38 Annotation: Subtype: Link Rect: 179, 29, 239, 38 Annotation: Subtype: Link Rect: 415, 29, 551, 38 Page: Sequence: 14 Annotations: Annotation: Subtype: Link Rect: 93, 697, 186, 706 Annotation: Subtype: Link Rect: 250, 678, 293, 687 Annotation: Subtype: Link Rect: 53, 669, 82, 677 Annotation: Subtype: Link Rect: 53, 641, 153, 649 Annotation: Subtype: Link Rect: 146, 621, 239, 631 Annotation: Subtype: Link Rect: 53, 584, 149, 593 Annotation: Subtype: Link Rect: 168, 545, 274, 555 Annotation: Subtype: Link Rect: 177, 518, 256, 526 Annotation: Subtype: Link Rect: 252, 489, 293, 498 Annotation: Subtype: Link Rect: 53, 479, 121, 489 Annotation: Subtype: Link Rect: 53, 451, 160, 460 Annotation: Subtype: Link Rect: 112, 423, 226, 432 Annotation: Subtype: Link Rect: 79, 395, 147, 403 Annotation: Subtype: Link Rect: 53, 366, 172, 375 Annotation: Subtype: Link Rect: 104, 328, 197, 337 Annotation: Subtype: Link Rect: 90, 281, 208, 290 Annotation: Subtype: Link Rect: 53, 243, 164, 252 Annotation: Subtype: Link Rect: 251, 224, 293, 233 Annotation: Subtype: Link Rect: 53, 214, 142, 223 Annotation: Subtype: Link Rect: 155, 177, 233, 186 Annotation: Subtype: Link Rect: 213, 148, 293, 157 Annotation: Subtype: Link Rect: 53, 139, 87, 147 Annotation: Subtype: Link Rect: 251, 110, 293, 119 Annotation: Subtype: Link Rect: 53, 101, 125, 110 Annotation: Subtype: Link Rect: 394, 698, 490, 706 Annotation: Subtype: Link Rect: 526, 669, 551, 678 Annotation: Subtype: Link Rect: 312, 661, 372, 668 Annotation: Subtype: Link Rect: 455, 632, 533, 640 Annotation: Subtype: Link Rect: 460, 612, 550, 621 Annotation: Subtype: Link Rect: 425, 593, 540, 602 Annotation: Subtype: Link Rect: 348, 556, 461, 564 Annotation: Subtype: Link Rect: 472, 527, 551, 536 Annotation: Subtype: Link Rect: 312, 518, 335, 526 Annotation: Subtype: Link Rect: 361, 489, 453, 498 Annotation: Subtype: Link Rect: 537, 470, 551, 479 Annotation: Subtype: Link Rect: 312, 461, 410, 470 Annotation: Subtype: Link Rect: 399, 433, 495, 441 Annotation: Subtype: Link Rect: 537, 413, 551, 422 Annotation: Subtype: Link Rect: 312, 404, 399, 413 Annotation: Subtype: Link Rect: 363, 375, 448, 384 Annotation: Subtype: Link Rect: 404, 356, 480, 366 Annotation: Subtype: Link Rect: 390, 329, 478, 337 Annotation: Subtype: Link Rect: 419, 290, 510, 299 Annotation: Subtype: Link Rect: 455, 271, 551, 280 Annotation: Subtype: Link Rect: 312, 263, 337, 270 Annotation: Subtype: Link Rect: 381, 224, 492, 233 Annotation: Subtype: Link Rect: 442, 195, 545, 205 Annotation: Subtype: Link Rect: 481, 176, 551, 186 Annotation: Subtype: Link Rect: 312, 169, 325, 176 Annotation: Subtype: Link Rect: 423, 138, 515, 148 Annotation: Subtype: Link Rect: 476, 111, 551, 119 Annotation: Subtype: Link Rect: 312, 101, 352, 110 Annotation: Subtype: Link Rect: 43, 29, 176, 38 Annotation: Subtype: Link Rect: 179, 29, 239, 38 Annotation: Subtype: Link Rect: 415, 29, 551, 38 Page: Sequence: 15 Annotations: Annotation: Subtype: Link Rect: 149, 698, 228, 706 Annotation: Subtype: Link Rect: 142, 660, 256, 668 Annotation: Subtype: Link Rect: 268, 641, 293, 649 Annotation: Subtype: Link Rect: 53, 631, 119, 640 Annotation: Subtype: Link Rect: 134, 593, 232, 602 Annotation: Subtype: Link Rect: 237, 564, 293, 574 Annotation: Subtype: Link Rect: 53, 557, 73, 564 Annotation: Subtype: Link Rect: 99, 527, 171, 536 Annotation: Subtype: Link Rect: 214, 489, 293, 498 Annotation: Subtype: Link Rect: 53, 481, 70, 488 Annotation: Subtype: Link Rect: 53, 451, 202, 460 Annotation: Subtype: Link Rect: 187, 423, 282, 432 Annotation: Subtype: Link Rect: 100, 395, 245, 403 Annotation: Subtype: Link Rect: 53, 357, 277, 366 Annotation: Subtype: Link Rect: 133, 329, 219, 337 Annotation: Subtype: Link Rect: 93, 290, 188, 299 Annotation: Subtype: Link Rect: 118, 271, 239, 280 Annotation: Subtype: Link Rect: 214, 243, 293, 252 Annotation: Subtype: Link Rect: 53, 234, 80, 242 Annotation: Subtype: Link Rect: 53, 205, 136, 214 Annotation: Subtype: Link Rect: 236, 186, 293, 195 Annotation: Subtype: Link Rect: 53, 178, 113, 185 Annotation: Subtype: Link Rect: 486, 687, 551, 697 Annotation: Subtype: Link Rect: 312, 679, 349, 687 Annotation: Subtype: Link Rect: 454, 641, 551, 649 Annotation: Subtype: Link Rect: 312, 632, 334, 639 Annotation: Subtype: Link Rect: 312, 593, 407, 602 Annotation: Subtype: Link Rect: 509, 574, 551, 583 Annotation: Subtype: Link Rect: 312, 565, 384, 574 Annotation: Subtype: Link Rect: 509, 536, 551, 545 Annotation: Subtype: Link Rect: 312, 528, 362, 535 Annotation: Subtype: Link Rect: 495, 508, 551, 517 Annotation: Subtype: Link Rect: 312, 500, 352, 507 Annotation: Subtype: Link Rect: 472, 470, 551, 479 Annotation: Subtype: Link Rect: 312, 462, 334, 469 Annotation: Subtype: Link Rect: 508, 432, 551, 441 Annotation: Subtype: Link Rect: 312, 423, 391, 431 Annotation: Subtype: Link Rect: 312, 385, 430, 394 Annotation: Subtype: Link Rect: 339, 214, 366, 224 Annotation: Subtype: Link Rect: 366, 214, 398, 224 Annotation: Subtype: Link Rect: 398, 214, 434, 224 Annotation: Subtype: Link Rect: 434, 214, 457, 224 Annotation: Subtype: Link Rect: 458, 214, 485, 224 Annotation: Subtype: Link Rect: 43, 29, 176, 38 Annotation: Subtype: Link Rect: 179, 29, 239, 38 Annotation: Subtype: Link Rect: 415, 29, 551, 38 Checksum: 0d55c0ba Type: CRC32 Checksum: c2830378c8bc9ae8520e816aa655ab5d Type: MD5 Checksum: a210145fc7321e6dce17e830036ef89e59b3b005 Type: SHA-1