328a88328a1b4942bf7586221c7e7bfa pmc_29348614.pdf aea28ec3494bc4afbcfa25c17d2bde37ebff4b92 pmc_29348614.pdf 40c17f91af8531a729d039c20414872075eeb3ec047597d6f4d5a03d1c62ed0f pmc_29348614.pdf Title: Noise-induced bistability in the fate of cancer phenotypic quasispecies: a bit-strings approach Subject: Scientific Reports, doi:10.1038/s41598-018-19552-2 Keywords: Author: Josep Sardanyamp#x000E9;s Creator: Springer Producer: iText® 5.3.5 ©2000-2012 1T3XT BVBA (AGPL-version) CreationDate: Tue Jan 9 13:11:12 2018 CET ModDate: Fri Jan 12 11:28:44 2018 CET Tagged: no UserProperties: no Suspects: no Form: AcroForm JavaScript: no Pages: 11 Encrypted: no Page size: 595.276 x 782.362 pts Page rot: 0 File size: 4688572 bytes Optimized: no PDF version: 1.4 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- ZBIDGU+Corbel CID TrueType Identity-H yes yes yes 487 0 MPEZGU+TimesNewRomanPSMT Type 1C WinAnsi yes yes yes 488 0 EuclidSymbol Type 1C Custom yes no yes 167 0 QNWFGG+Corbel-Bold2 Type 1C WinAnsi yes yes yes 168 0 ASDKWR+Corbel2 Type 1C WinAnsi yes yes yes 107 0 HQIUOE+Corbel-Bold CID TrueType Identity-H yes yes yes 171 0 MinionPro-Regular Type 1C Custom yes no yes 108 0 QNWFGG+Corbel-Bold2 Type 1C WinAnsi yes yes yes 387 0 ASDKWR+Corbel2 Type 1C WinAnsi yes yes yes 388 0 ZBIDGU+Corbel CID TrueType Identity-H yes yes yes 520 0 MyriadPro-It Type 1C WinAnsi yes no yes 390 0 MinionPro-It Type 1C Custom yes no yes 105 0 EuclidSymbol-Italic Type 1C Custom yes no yes 106 0 ZBIDGU+Corbel CID TrueType Identity-H yes yes yes 389 0 YELKSW+EuclidExtra CID TrueType Identity-H yes yes yes 166 0 EFPZYK+STIXGeneral-Regular Type 1C Custom yes yes no 169 0 STIXGeneral-Italic Type 1C Custom yes no no 170 0 ZBIDGU+Corbel CID TrueType Identity-H yes yes yes 399 0 MyriadPro-It Type 1C WinAnsi yes no yes 400 0 MinionPro-Bold Type 1C WinAnsi yes no yes 206 0 OLAIDQ+EuclidMathTwo CID TrueType Identity-H yes yes yes 224 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2022-11-09 03:06:50 CET RepresentationInformation: pmc_29348614.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2018-03-05 03:50:19 CET Size: 4688572 Format: PDF Version: 1.4 Status: Well-Formed, but not valid SignatureMatches: PDF-hul ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_19552.indd: 4. Hanahan, D. & Weinberg, R. A. Hallmarks of Cancer: The Next Generation. Cell 144, 646–670 (2011). :70' cannot be found Offset: 4305975 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_19552.indd: 51. Sardanyés, J., Martínez, R., Simó, C. & Solé, R. V. Abrupt transitions to tumor extinction: a phenotypic quasispecies model. J. Math. Biol. 74(7), 1589–1609 (2017). :82' cannot be found Offset: 4305975 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_19552.indd: 51. Sardanyés, J., Martínez, R., Simó, C. & Solé, R. V. Abrupt transitions to tumor extinction: a phenotypic quasispecies model. J. Math. Biol. 74(7), 1589–1609 (2017). :89' cannot be found Offset: 4305975 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_19552.indd: 51. Sardanyés, J., Martínez, R., Simó, C. & Solé, R. V. Abrupt transitions to tumor extinction: a phenotypic quasispecies model. J. Math. Biol. 74(7), 1589–1609 (2017). :90' cannot be found Offset: 4305975 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_19552.indd:Figure 1. (a) Mean population equilibria obtained from the stochastic bit-strings model using large population sizes (N = 5 × 104 cells in the main panel; N = 105 cells in the inset). All data points are the mean population values (±S:91' cannot be found Offset: 4305975 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_19552.indd:Figure 1. (a) Mean population equilibria obtained from the stochastic bit-strings model using large population sizes (N = 5 × 104 cells in the main panel; N = 105 cells in the inset). All data points are the mean population values (±:92' cannot be found Offset: 4305975 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_19552.indd:Figure 1. (a) Mean population equilibria obtained from the stochastic bit-strings model using large population sizes (N = 5 × 104 cells in the main panel; N = 105 cells in the inset). All data points are the mean population values (±:93' cannot be found Offset: 4305975 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_19552.indd:Figure 1. (a) Mean population equilibria obtained from the stochastic bit-strings model using large population sizes (N = 5 × 104 cells in the main panel; N = 105 cells in the inset). All data points are the mean population values (:94' cannot be found Offset: 4305975 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_19552.indd: 51. Sardanyés, J., Martínez, R., Simó, C. & Solé, R. V. Abrupt transitions to tumor extinction: a phenotypic quasispecies model. J. Math. Biol. 74(7), 1589–1609 (2017). :98' cannot be found Offset: 4305975 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_19552.indd:Figure 1. (a) Mean population equilibria obtained from the stochastic bit-strings model using large population sizes (N = 5 × 104 cells in the main panel; N = 105 cells in the inset). All data points are the mean population values :99' cannot be found Offset: 4305975 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_19552.indd:Figure 1. (a) Mean population equilibria obtained from the stochastic bit-strings model using large population sizes (N = 5 × 104 cells in the main panel; N = 105 cells in the inset). All data points are the mean population values:100' cannot be found Offset: 4305975 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_19552.indd:Figure 1. (a) Mean population equilibria obtained from the stochastic bit-strings model using large population sizes (N = 5 × 104 cells in the main panel; N = 105 cells in the inset). All data points are the mean population value:101' cannot be found Offset: 4305975 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_19552.indd:Figure 1. (a) Mean population equilibria obtained from the stochastic bit-strings model using large population sizes (N = 5 × 104 cells in the main panel; N = 105 cells in the inset). All data points are the mean population valu:102' cannot be found Offset: 4305975 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_19552.indd:Figure 1. (a) Mean population equilibria obtained from the stochastic bit-strings model using large population sizes (N = 5 × 104 cells in the main panel; N = 105 cells in the inset). All data points are the mean population val:103' cannot be found Offset: 4305975 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_19552.indd:Figure 2. (a) Mean population equilibria setting N = 500 cells. Each data point is the mean (±SD) population computed at τ = 25000 generations averaged over 25 independent replicas. (b) Stochastic trajectories projected in the space (H:104' cannot be found Offset: 4305975 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_19552.indd:Figure 1. (a) Mean population equilibria obtained from the stochastic bit-strings model using large population sizes (N = 5 × 104 cells in the main panel; N = 105 cells in the inset). All data points are the mean population va:105' cannot be found Offset: 4305975 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_19552.indd:Figure 1. (a) Mean population equilibria obtained from the stochastic bit-strings model using large population sizes (N = 5 × 104 cells in the main panel; N = 105 cells in the inset). All data points are the mean population v:106' cannot be found Offset: 4305975 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_19552.indd: 51. Sardanyés, J., Martínez, R., Simó, C. & Solé, R. V. Abrupt transitions to tumor extinction: a phenotypic quasispecies model. J. Math. Biol. 74(7), 1589–1609 (2017). :107' cannot be found Offset: 4305975 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_19552.indd:Figure 2. (a) Mean population equilibria setting N = 500 cells. Each data point is the mean (±SD) population computed at τ = 25000 generations averaged over 25 independent replicas. (b) Stochastic trajectories projected in the space (H:108' cannot be found Offset: 4305975 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_19552.indd:Figure 2. (a) Mean population equilibria setting N = 500 cells. Each data point is the mean (±SD) population computed at τ = 25000 generations averaged over 25 independent replicas. (b) Stochastic trajectories projected in the space (:109' cannot be found Offset: 4305975 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_19552.indd: 51. Sardanyés, J., Martínez, R., Simó, C. & Solé, R. V. Abrupt transitions to tumor extinction: a phenotypic quasispecies model. J. Math. Biol. 74(7), 1589–1609 (2017). :95' cannot be found Offset: 4305975 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_19552.indd:Figure 2. (a) Mean population equilibria setting N = 500 cells. Each data point is the mean (±SD) population computed at τ = 25000 generations averaged over 25 independent replicas. (b) Stochastic trajectories projected in the space (:112' cannot be found Offset: 4305975 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_19552.indd:Figure 1. (a) Mean population equilibria obtained from the stochastic bit-strings model using large population sizes (N = 5 × 104 cells in the main panel; N = 105 cells in the inset). All data points are the mean population :113' cannot be found Offset: 4305975 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_19552.indd:Figure 3. (a) Probability of achieving the healthy absorbing state, PH, at increasing per-bit mutation probability (μb). The main panel shows five overlapped curves for different population sizes N. The inset displays the same re:114' cannot be found Offset: 4305975 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_19552.indd:Figure 3. (a) Probability of achieving the healthy absorbing state, PH, at increasing per-bit mutation probability (μb). The main panel shows five overlapped curves for different population sizes N. The inset displays the same r:115' cannot be found Offset: 4305975 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_19552.indd:Figure 3. (a) Probability of achieving the healthy absorbing state, PH, at increasing per-bit mutation probability (μb). The main panel shows five overlapped curves for different population sizes N. The inset displays the same:117' cannot be found Offset: 4305975 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_19552.indd:Figure 3. (a) Probability of achieving the healthy absorbing state, PH, at increasing per-bit mutation probability (μb). The main panel shows five overlapped curves for different population sizes N. The inset displays the sam:118' cannot be found Offset: 4305975 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_19552.indd:Figure 3. (a) Probability of achieving the healthy absorbing state, PH, at increasing per-bit mutation probability (μb). The main panel shows five overlapped curves for different population sizes N. The inset displays the sa:119' cannot be found Offset: 4305975 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_19552.indd:Figure 3. (a) Probability of achieving the healthy absorbing state, PH, at increasing per-bit mutation probability (μb). The main panel shows five overlapped curves for different population sizes N. The inset displays the s:120' cannot be found Offset: 4305975 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_19552.indd:Figure 4. Mean times (in number of generations τ) needed for trajectories starting at S0(τ = 0) = 0.9 and S4(τ = 0) = 0.1 to achieve the tumor absorbing state Tas (a) and the healthy absorbing state Has (b) at incre:125' cannot be found Offset: 4305975 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_19552.indd:Figure 4. Mean times (in number of generations τ) needed for trajectories starting at S0(τ = 0) = 0.9 and S4(τ = 0) = 0.1 to achieve the tumor absorbing state Tas (a) and the healthy absorbing state Has (b) at incr:126' cannot be found Offset: 4305975 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_19552.indd:Figure 4. Mean times (in number of generations τ) needed for trajectories starting at S0(τ = 0) = 0.9 and S4(τ = 0) = 0.1 to achieve the tumor absorbing state Tas (a) and the healthy absorbing state Has (b) at in:128' cannot be found Offset: 4305975 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_19552.indd:Figure 4. Mean times (in number of generations τ) needed for trajectories starting at S0(τ = 0) = 0.9 and S4(τ = 0) = 0.1 to achieve the tumor absorbing state Tas (a) and the healthy absorbing state Has (b) at i:129' cannot be found Offset: 4305975 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_19552.indd: 21. Solé, R. V. Phase transitions in unstable cancer cell populations. Eur. J. Phys. B. 35, 117–124 (2003). :135' cannot be found Offset: 4305975 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_19552.indd: 25. Solé, R. V., Valverde, S., Rodriguez-Caso, C. & Sardanyés, J. Can a minimal replicating construct be identified as the embodiment of cancer? Bioessays 36, 503–512 (2014). :162' cannot be found Offset: 4305975 ID: PDF-HUL-122 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'SpringerNature_SciRep_19552.indd: 51. Sardanyés, J., Martínez, R., Simó, C. & Solé, R. V. Abrupt transitions to tumor extinction: a phenotypic quasispecies model. J. Math. Biol. 74(7), 1589–1609 (2017). :167' cannot be found Offset: 4305975 MIMEtype: application/pdf PDFMetadata: Objects: 552 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: false CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseOutlines Language: EN Outlines: Item: Title: Noise-induced bistability in the fate of cancer phenotypic quasispecies: a bit-strings approach Children: Item: Title: Results Children: Item: Title: Summary of the mean field dynamics. Item: Title: Catastrophic extinction of tumor phenotypes. Item: Title: Impact of noise on the trans-heteroclinic transition. Item: Title: Transitory times near bifurcation threshold. Item: Title: Discussion Item: Title: Methods Children: Item: Title: Stochastic bit-strings model. Item: Title: Acknowledgements Item: Title: Figure 1 (a) Mean population equilibria obtained from the stochastic bit-strings model using large population sizes (N = 5 × 104 cells in the main panel N = 105 cells in the inset). Item: Title: Figure 2 (a) Mean population equilibria setting N = 500 cells. Item: Title: Figure 3 (a) Probability of achieving the healthy absorbing state, PH, at increasing per-bit mutation probability (μb). Item: Title: Figure 4 Mean times (in number of generations τ) needed for trajectories starting at S0(τ = 0) = 0. 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Identity Supplement: 0 FontDescriptor: FontName: YELKSW+EuclidExtra Flags: Symbolic FontBBox: -126, -327, 1573, 962 FontFile2: true XMP: application/pdf doi:10.1038/s41598-018-19552-2 Springer US Scientific Reports, doi:10.1038/s41598-018-19552-2 Noise-induced bistability in the fate of cancer phenotypic quasispecies: a bit-strings approach Josep Sardanyamp#x000E9;s Tomamp#x000E1;s Alarcamp#x000F3;n 10.1038/s41598-018-19552-2 http://dx.doi.org/10.1038/s41598-018-19552-2 journal Scientific Reports © 2018, The Author(s) 2045-2322 10.1038/s41598-018-19552-2 Springer 2018-01-12T11:28:44+01:00 2018-01-09T17:41:12+05:30 2018-01-12T11:28:44+01:00 True iText® 5.3.5 ©2000-2012 1T3XT BVBA (AGPL-version) VoR uuid:63c114e3-845f-4cb4-b040-7984fec4d0c1 uuid:0f2def42-ea0c-4c65-8b1a-15aef0c38abe default 1 converted uuid:bb9a40a2-67b3-41ac-ba75-acce5b348fa0 converted to PDF/A-2b pdfToolbox 2018-01-09T17:42:08+05:30 2 B http://ns.adobe.com/pdf/1.3/ pdf Adobe PDF Schema internal A name object indicating 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If used as a dc:identifier, the URI form should be captured, and the bare identifier should also be captured using prism:doi. If an alternate unique identifier is used as the required dc:identifier, then the DOI should be specified as a bare identifier within prism:doi only. If the URL associated with a DOI is to be specified, then prism:url may be used in conjunction with prism:doi in order to provide the service endpoint (i.e. the URL). doi Text external ISSN for an electronic version of the issue in which the resource occurs. Permits publishers to include a second ISSN, identifying an electronic version of the issue in which the resource occurs (therefore e(lectronic)Issn. If used, prism:eIssn MUST contain the ISSN of the electronic version. See prism:issn. issn Text external Title of the magazine, or other publication, in which a resource was/will be published. Typically this will be used to provide the name of the magazine an article appeared in as metadata for the article, along with information such as the article title, the publisher, volume, number, and cover date. Note: Publication name can be used to differentiate between a print magazine and the online version if the names are different such as “magazine” and “magazine.com.” publicationName Text external This element provides the url for an article or unit of content. The attribute platform is optionally allowed for situations in which multiple URLs must be specified. PRISM recommends that a subset of the PCV platform values, namely “mobile” and “web”, be used in conjunction with this element. NOTE: PRISM recommends against the use of the #other value allowed in the PRISM Platform controlled vocabulary. In lieu of using #other please reach out to the PRISM group at prism-wg@yahoogroups.com to request addition of your term to the Platform Controlled Vocabulary. url Text http://www.niso.org/schemas/jav/1.0/ jav NISO external Values for Journal Article Version are one of the following: AO = Author’s Original SMUR = Submitted Manuscript Under Review AM = Accepted Manuscript P = Proof VoR = Version of Record CVoR = Corrected Version of Record EVoR = Enhanced Version of Record journal_article_version Closed Choice of Text Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Rect: 315, 344, 318, 332 Flags: Print AppearanceDictionary: true Destination: 360 Annotation: Subtype: Link Rect: 320, 344, 322, 332 Flags: Print AppearanceDictionary: true Destination: 360 Annotation: Subtype: Link Rect: 366, 334, 368, 322 Flags: Print AppearanceDictionary: true Destination: 360 Annotation: Subtype: Link Rect: 370, 334, 373, 322 Flags: Print AppearanceDictionary: true Destination: 360 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