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Towards simulating a cell adhesion site at angstrom resolution

Applicant Vogel Viola
Number 133122
Funding scheme Project funding (Div. I-III)
Research institution Departement Materialwissenschaft ETH Zürich
Institution of higher education ETH Zurich - ETHZ
Main discipline Molecular Biology
Start/End 01.03.2011 - 28.02.2014
Approved amount 537'000.00
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All Disciplines (2)

Discipline
Molecular Biology
Cellular Biology, Cytology

Keywords (7)

mechanobiology; mechanical forces;; integrins; molecular dynamics simulations; forcebearing protein networks;

Lay Summary (German)

Lead
Lay summary
HintergrundIn Gewebe eingebettete Zellen sind ständig internen und externen mechanischen Kräften ausgesetzt. Die im Cytoskelett (ein kontraktiles Proteinnetzwerk, das der Zelle Struktur & Bewegungsfähigkeit verleiht) entstehenden Kräfte werden durch Zelladhäsionsproteine in die extrazelluläre Matrix, d. h. in das umliegende Gewebe übertragen. Diese Kräfte können zu erheblichen strukturelle Veränderungen dieser Zelladhäsionsproteine führen, was wiederum deren biochemische Aktivität verändern kann. Die Zelle verfügt damit über einen Sensormechanismus, der ihr wichtige Informationen über die Beschaffenheit ihres Substrats, z.B. dessen Härte, liefern kann. Diese Information bestimmt massgeblich das weitere Schicksal der Zelle. Zudem verändern die von den Zellen generierten Kräfte die molekulare Struktur einiger extrazellulären Matrixproteine, was ebenfalls biochemische Prozesse in der Zelle oder das Risiko von bakteriellen Infektionen beeinflussen kann. Die zugrundeliegenden molekularen Strukturen von Proteinen des Zelladhäsionskomplexes sind teilweise in atomarer Auflösung verfügbar. Diese Gleichgewichtsstrukturen liefern jedoch nur ein statisches Bild der Wirklichkeit. Viele Details über die durch mechanische Kraft induzierten strukturellen Veränderung der involvierten Proteine und deren Dynamik sind nach wie vor unbekannt. Das ZielMittels Molekulardynamik-Simulationen sind wir in der Lage, den Effekt mechanischer Kraft auf die Struktur der Zelladhäsionsproteine zu untersuchen. Im Gegensatz zu experimentellen Ansätzen erlaubt uns diese Technik, die strukturellen Veränderungen der Moleküle in atomarer Auflösung zu verfolgen. Sämtliche Simulationen sind sehr rechenintensiv und werden im Hochleistungs-Rechenzentrum der Schweiz CSCS durchgeführt. Die daraus gewonnenen Erkenntisse werden nach Möglichkeit experimentell verifiziert oder geben Anstoss zu neuen Experimenten.BedeutungDie von uns untersuchten Proteine spielen zentrale Rollen für die Zelladhäsion an Biomaterialien oder in natürlichem Gewebe, bei der Übermittlung von biochemischen Signalen, sowie in Infektions- und Wundheilungsprozessen. Defekte oder Mutationen von Zelladhäsionsproteinen können zu verschiedensten Krankheiten führen. Unsere Grundlagenforschung schafft daher nicht nur neues Wissen, sondern hat auch das Potential, neue pharmakologische Ansätze aufzuzeigen.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Synergistic interactions of blood-borne immune cells, fibroblasts and extracellular matrix drive repair in an in vitro peri-implant wound healing model
Burkhardt Melanie A, Waser Jasmine, Milleret Vincent, Gerber Isabel Gerber, Emmert Maximilian Y, Foolen Jasper, Hoerstrup Simon P., Schlotting Falko, Vogel Viola (2016), Synergistic interactions of blood-borne immune cells, fibroblasts and extracellular matrix drive repair in an in vitro peri-implant wound healing model, in Scientific Reports, 6, 1-15.
Differential basal-to-apical accessibility of lamin A/C epitopes in the nuclear lamina regulated by changes in cytoskeletal tension
Ihalainen Teemu O., Aires Lina, Herzog Florian, Schwartlander Ruth, Moller Jens, Vogel Viola (2015), Differential basal-to-apical accessibility of lamin A/C epitopes in the nuclear lamina regulated by changes in cytoskeletal tension, in Nature Materials, 4, 1252-1261.
Ectokinases as novel cancer markers and drug targets in cancer therapy
Yalak Garif, Vogel Viola (2015), Ectokinases as novel cancer markers and drug targets in cancer therapy, in Cancer Medicine, 4(3), 404-–414.
Functional Modification of Fibronectin by N-TerminalFXIIIa-Mediated Transamidation
Früh Susanna Maria, Spycher Philipp R., Mitsi Maria, Burkhardt Melanie A., Vogel Viola, Schön Ingmar (2015), Functional Modification of Fibronectin by N-TerminalFXIIIa-Mediated Transamidation, in ChemBioChem, 15, 1481-1486.
Heparin-induced conformational changes of fibronectin within the extracellular matrix promote hMSC osteogenic differentiation
Bojun Li, Zhe Lin, Mitsi Maria, Zhang Yang, Vogel Viola (2015), Heparin-induced conformational changes of fibronectin within the extracellular matrix promote hMSC osteogenic differentiation, in Biomaterials Science, 3(1), 73-84.
The ultrastructure of fibronectin fibers pulled from a protein monolayer at the air-liquid interface and the mechanism of the sheet-to-fiber transition
Mitsi Maria, Handschin Stephan, Gerber Isabel, Schwartlander Ruth, Klotzsch Enrico, Wepf Roger, Vogel Viola (2015), The ultrastructure of fibronectin fibers pulled from a protein monolayer at the air-liquid interface and the mechanism of the sheet-to-fiber transition, in Biomaterials, 36, 66-79.
Multiple Steps to Activate FAK's Kinase Domain
Herzog Florian A., Vogel Viola (2013), Multiple Steps to Activate FAK's Kinase Domain, in Biophysical Journal, 104(11), 2521-2529.
The Yin-Yang of Rigidity Sensing: How Forces and Mechanical Properties Regulate the Cellular Response to Materials
Schoen Ingmar, Smith Michael L., Vogel Viola (2013), The Yin-Yang of Rigidity Sensing: How Forces and Mechanical Properties Regulate the Cellular Response to Materials, in Annual Reviews, 43, 589-618.
Engineering mechanosensitive multivalent receptor-ligand interactions: Why the nanolinker regions of bacterial adhesins matter
Hertig S, Chabria M, Vogel V (2012), Engineering mechanosensitive multivalent receptor-ligand interactions: Why the nanolinker regions of bacterial adhesins matter, in Nano Letters, 12(10), 5162-5168.
Extracellular phosphorylation and phosphorylated proteins: Not just curiosities but physiologically important
Yalak G, Vogel V (2012), Extracellular phosphorylation and phosphorylated proteins: Not just curiosities but physiologically important, in Science Signaling, 5(255), re7.
Fibers with integrated mechanochemical switches: Minimalistic design principles derived from fibronectin
Peleg O, Savin T, Kolmakov GV, Salib IG, Balazs AC, Kröger M, Vogel V (2012), Fibers with integrated mechanochemical switches: Minimalistic design principles derived from fibronectin, in Biophysical Journal, 103(9), 1909-1918.

Collaboration

Group / person Country
Types of collaboration
Prof. Daniel Muller / ETH Basel, Dept. Biosysteme Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. Mike Dustin / New York University, Medical School United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. Beth Pruitt / Stanford University; Mechanical Engineering United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. Chris S. Chen / University of Pennsylvania, Skirkanich Prof. of Innovation in Bioengineering United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. Bernhard Wehrle-Haller / Université de Genève, Physiologie cellulaire et métabolisme Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Dr. Martin Behe / Paul Scherrer Institut PSI Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. Simon P. Hoerstrup / Universität Zurich, Regenerative Medicine Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
CSCS Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. Dr. Peter Fratzl / Max-Planck-Institut fur Kolloid- und Grenzflächenforschung Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. Lorenz Meinel/Julius-Maximilians-Universität Wurzburg Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
58th Annual Meeting of the Biophysical Society Poster How structural fluctuations of the ATP pocket influence the catalytic cycle of FAK 15.02.2014 San Francisco, United States of America Vogel Viola; Herzog Florian;
Biophysical Society 58th Annual Meeting „ Bridging the Sciences to Explore Biology “ Talk given at a conference How Cells exploit Forces to sense and respond to their Environments 15.02.2014 San Francisco, United States of America Vogel Viola;
NIM - Workshop Young Ideas in Nanoscience Talk given at a conference Nanomechanics by which cells explore their environments 19.11.2013 München, Germany Vogel Viola;
The Abdus Salam Intern. Centre for Theoretical Physics: Advanced School on Synchrotron Radiation Techniques and Nanotechnology: A Synergic Approach to Life Sciences and Medicine Talk given at a conference Lecture 1: “Proteins as mechano-chemical switches” 11.11.2013 Stellenbosch, South Africa Vogel Viola;
The Abdus Salam Intern. Centre for Theoretical Physics: Advanced School on Synchrotron Radiation Techniques and Nanotechnology: A Synergic Approach to Life Sciences and Medicine Talk given at a conference Lecture 2: “How the stretching of proteins regulates cell functions 11.11.2013 Stellenbosch, South Africa Vogel Viola;
The Abdus Salam Intern. Centre for Theoretical Physics: Advanced School on Synchrotron Radiation Techniques and Nanotechnology: A Synergic Approach to Life Sciences and Medicine Talk given at a conference Lecture 3: “Nanomechanics by which cells explore their environments and chase their pray” 11.11.2013 Stellenbosch, South Africa Vogel Viola;
5th European Cell Mechanics Meeting 2013 Poster Multiple Steps to Activate the Kinase Domain of FAK: Adaption to Confined Environments? 28.09.2013 Obergurgl, Austria Vogel Viola; Herzog Florian;
Cell Mech Conference 2013, European Science Foundation (ESF) Talk given at a conference How cells exploit forces to recognize physical properties of their environments 28.09.2013 Obergurgl, Austria Vogel Viola;
Symposium Molecular motors: Multiscale Motility of Molecular Motors Talk given at a conference Tensile forces synchronize filopopial and lamellipodial motor activities 22.09.2013 Potsdam, Germany Vogel Viola;
Summer Workshop "Mechanics in Biology", Julius Wolff Institute Talk given at a conference Summer Workshop "Mechanics in Biology", Julius Wolff Institute 16.09.2013 Berlin, Germany Vogel Viola;
COST European Cooperation in Science and Technology, 3rd ECMNET Conference "Brain Extracellular Matrix in Health and Disease" Talk given at a conference What role do mechanical forces play in regulating angiogenesis within the brain? 12.09.2013 Opalencia, Poland Vogel Viola;
AOER Symposium, "Where Science meets Clinics 2013" Talk given at a conference How Mechanobiology Inspires New Approaches on the path form basic Science to the Clincs 05.09.2013 Davos, Switzerland Vogel Viola;
The Living Cell Conference Talk given at a conference How Cells Exploit Mechanical Forces to Recognize Physical Aspects of their Environments 22.07.2013 Sheffield, Great Britain and Northern Ireland Vogel Viola;
European Biophysics Congress, EBSA2013 Talk given at a conference Mechanobiology: From molecular zippers tot he recognition of nanotopographies“ 13.07.2013 Lisbon, Portugal Vogel Viola;
WE Heraeus Seminar on Micro- and Nanostructured Interfaces for Biological and Medical Research 2013 Talk given at a conference How Can Cells Exploit Forces to Recognize Nanoscale Templates and Topographies? 01.07.2013 Bad Honnef, Germany Vogel Viola;
Clinical Nanomedicine & Target Medicine Talk given at a conference Nanomechanics - Future Targets in Molecular Medicine? 23.06.2013 Basel, Switzerland Vogel Viola;
How Cell Recognize and Remodel their Micro-niches Talk given at a conference How Cells and Bacteria Exploit Proteins as Mechano-Chemical Signaling Switches 03.04.2013 Urbana-Champaign, United States of America Vogel Viola;
Select Bio; Single Cell Analysis Europe Conference Talk given at a conference How Cell Recognize and Remodel their Micro-niches 04.03.2013 Barcelona, Spain Vogel Viola;
Solvay Chair, Lecture Talk given at a conference From Tissue Engineering to Cancer: Mechano-regulated recognition processes in health and disease 28.02.2013 Brussel, Belgium Vogel Viola;
Fibronectin, Integrins & Related Molecules Poster Extracellular Phosphorylation of Fibronectin, Integrins and Related Molecules 10.02.2013 Ventura, CA, United States of America Yalak Garif; Vogel Viola;
Distinguished Seminar: Proteins as Mechano-Chemical Signaling Switches Talk given at a conference Proteins as mechano-Chemical Signaling Switches 03.02.2013 Boston, United States of America Vogel Viola;
Department of Biomedical Engineering at Columbia University Talk given at a conference Distinguished Seminar: Proteins as Mechano-Chemical Signaling Switches 31.01.2013 New York, United States of America Vogel Viola;
Annual Meeting, the American Society for Cell Biology, ASCB Talk given at a conference „How cells exploit extracellular matrix fibrils as mechano-chemical signal coverters“ 16.12.2012 San Francisco, United States of America Vogel Viola;
Solvay Chair, Lecture 3 Talk given at a conference Stretching and Breaking Bonds: how cells recognize material properties 21.11.2012 Brussels, Belgium Vogel Viola;
Solvay Chair, Lecture 2 Talk given at a conference Proteins as Mechano-Chemical Switches: how Nature exploits mechanical forces 21.11.2012 Brussels, Belgium Vogel Viola;
Exciting Biologies: Forces in Biology Poster Probing the mechanical strain state of fibronectin fibrils: peptides derived from bacterial adhesins 04.10.2012 Dublin, Ireland Vogel Viola; Chabria Mamta;
SFB‐613 International Symposium on “Physics of Single‐Molecule Processes and Molecular Recognition” Talk given at a conference Mechanoregulated adhesion mechanisms 28.09.2012 Bielefeld, Germany Vogel Viola;
User Day of the Swiss Supercomputing Center CSCS Poster Probing the mechanical strain state of fibronectin fibrils - peptides derived from bacterial adhesins 20.09.2012 Lugano, Switzerland Chabria Mamta; Vogel Viola;
User Day of the Swiss Supercomputing Center CSCS Poster Allosteric Regulation of the ATP-Binding Pocket in the Focal Adhesion Kinase 20.09.2012 Lugano, Switzerland Herzog Florian; Vogel Viola;
Workshop Institute of Biomedical Technology, University of Tampere Talk given at a conference How cells recognize material properties 18.09.2012 Tampere, Finland Vogel Viola;
Physics Meets Biology Conference Talk given at a conference Mechno-regulated recognition processes 03.09.2012 Oxford, Great Britain and Northern Ireland Vogel Viola;
NanoBio Conference 2012 Talk given at a conference The forceful play of cells with extracellular matrix 23.07.2012 Seattle, United States of America Vogel Viola;
GRC: Single Molecule Approaches to Biology Talk given at a conference How cells exploit mechanical aspects of single molecules 15.07.2012 Mount Snow Resort, United States of America Vogel Viola;
GRC: Signal Transduction by Engineered Extracellular Matrices Talk given at a conference Mechanical signaling by extracellular matrix 08.07.2012 Biddeford, United States of America Vogel Viola;
8th Annual Workshop on Nano-science and Technology Talk given at a conference Keynote: How cells and bacteria exploit the nanomechanics of Proteins 26.06.2012 Tel Aviv, Israel Vogel Viola;
How Mechanical Forces Can Regulate the Extracellular Matrix Niche Talk given at a conference Catch bonds and other mechano-regulated bacterial adhesion mechanisms 25.06.2012 Tel Aviv, Israel Vogel Viola;
Stem Cell Symposium Talk given at a conference How Mechanical Forces Can Regulate the Extracellular Matrix Niche 22.06.2012 Zürich, Switzerland Vogel Viola;
Julius Springer forum on Applied Physics 2012 - Akademie der Künste Talk given at a conference Learning from bacteria: Mechano-biochemical nanoSwitches 20.06.2012 Berlin, Germany Vogel Viola;
IRTG - Soft Matter Science Talk given at a conference The forceful play of cells with extracellular matrix and bacteria 11.06.2012 Freiburg, Germany Vogel Viola;
Cell Adhesion Meeting 2012 -4ème colloque du club adhérence cellulaire Talk given at a conference Adhesion strength and mechanosensing 23.05.2012 Bordeaux, France Vogel Viola;
4th International Symposium Interface Biology of Implants Talk given at a conference The forceful play of cells with extracellular matrix and bacteria 10.05.2012 Rostock, Germany Vogel Viola;
2nd NanoToday Conference Talk given at a conference Proteins as Mechano-Chemical Nano Switches 11.12.2011 Hawaii, United States of America Vogel Viola;
4th International Conference on the Mechanics of Biomaterials and Tissues Talk given at a conference Exploiting the mchanobiology of extracellular matrix 11.12.2011 Hawaii, United States of America Vogel Viola;
Chains 2011 – Chemistry as Innovating Science Talk given at a conference Marie Curie Lecture 28.11.2011 Maarssen, Netherlands Vogel Viola;
Symposium Mechanobiology, RWTH Talk given at a conference How cells exploit the nanomechanics of proteins 10.11.2011 Aachen, Germany Vogel Viola;
TUBITAK-NSF-ESF Workshop Talk given at a conference Health Engineering-Inspired Physiology 19.10.2011 Istanbul, Turkey Vogel Viola;
CECAM-Workshop Talk given at a conference Mechanisms by which forces can switch the structure-function relationships of proteins 10.10.2011 Bremen, Germany Vogel Viola;
User Day of the Swiss Supercomputing Center CSCS Poster Engineering mechanosensitive interactions: Lessons learned from bacterial adhesins 23.09.2011 Lucerne, Switzerland, Switzerland Chabria Mamta; Vogel Viola;
MNE 2011 – 37th International Conference on Micro and Nano Engineering Talk given at a conference How cells exploit the nanomechanics of proteins 21.09.2011 Berlin, Germany Vogel Viola;
Bioengineering 11 Talk given at a conference Mechanotransduction Mechanisms 12.09.2011 London, Great Britain and Northern Ireland Vogel Viola;
ESB Talk given at a conference From Force to Function: Proteins as Mechanochemical Signal Converters 05.09.2011 Dublin, Ireland Vogel Viola;
Summer School Cellular Systems Talk given at a conference Mechanosignalising of the extracellular matrix 29.08.2011 Heidelberg, Germany Vogel Viola;
Symposium on Computer Models in Biomechanics: from Nano to Macro Poster Biological Mechanoresponsive Signal Converters: Deducing Minimalistic Designs 29.08.2011 Standford, California, USA, United States of America Peleg Orit; Vogel Viola;
Nachwuchsakademie Medizintechnik 2011 Talk given at a conference Innovative approaches meet traditional biomaterials 28.08.2011 Berlin, Germany Vogel Viola;
Cellular Nano-Science Conference Talk given at a conference Mechano-Chemical Switches 03.07.2011 Heidelberg, Germany Vogel Viola;
3rd ESF Summer School, Nanomedicine 2011 Talk given at a conference Tissue-Engineering –mechanical forces 23.06.2011 Lutherstadt, Germany Vogel Viola;
The 23rd Pezcoller Foundation Symposia, “Engineering influences in Cancer Research Talk given at a conference How cells exploit mechanical forces to regulate cell functions 15.06.2011 Trento, Italy Vogel Viola;
125 Jahre Schweizerische Zahnärzte-Gesellschaft SSO, Kongress 2011 Talk given at a conference Nanomedizin, die zweite Welle der erkenntnisgetriebenen Innovationen 26.05.2011 Luzern, Switzerland Vogel Viola;
Swiss NanoConvention 2011 Talk given at a conference How Can Cells Sense Mechanical Forces 18.05.2011 Baden, Switzerland Vogel Viola;
Institute for Molecules and Materials, IMM Symposium 2011 Talk given at a conference How do cell sense material properties? 15.05.2011 Nijmegen, Netherlands Vogel Viola;
Frauenhofer EMFT, “Systemintegration in der Mikrosystemetechnik” Talk given at a conference Proteine als mechanische Nanoschalter 10.05.2011 München, Germany Vogel Viola;
Gordon Research Conference: Fibronectins, Integrins and Related Molecules Poster Stretching fibronectin fibers disrupts binding of bacterial adhesins 01.05.2011 Florence, Italy, Italy Chabria Mamta; Vogel Viola;
Multiscale Computational Biomechanics Poster Biological Mechanoresponsive Signal Converters: Deducing Minimalistic Designs 12.04.2011 Zürich, Switzerland, Switzerland Vogel Viola; Peleg Orit;
DPG-Spring Meeting Talk given at a conference Stretching Proteins out of equilibrium: how extracellular matrix proteins serve as mechanotransducers 15.03.2011 Dresden, Germany Vogel Viola;


Communication with the public

Communication Title Media Place Year
Media relations: print media, online media Prof. Viola Vogel at the World Economic Forum 2013 in Davos Tagesanzeiger German-speaking Switzerland 2013
New media (web, blogs, podcasts, news feeds etc.) Viola Vogel Talkgast bei Giacobbo/Müller SRF1 German-speaking Switzerland 2013
Media relations: print media, online media Viola Vogel: Sie sucht in der Natur nach der Nanowelt Tagesanzeiger German-speaking Switzerland 2013
New media (web, blogs, podcasts, news feeds etc.) Viola Vogel: FIFA looking into the future of health International 2012

Awards

Title Year
Postdoctoral fellowship - Fellowship for prospective researchers 2013

Associated projects

Number Title Start Funding scheme
156931 Mechanotransduction processes, from the cell periphery to the nucleus, in 2D versus 3D microenvironments 01.10.2014 Interdisciplinary projects
116236 Towards simulating a cell adhesion site at angstrom resolution 01.01.2008 Project funding (Div. I-III)
116236 Towards simulating a cell adhesion site at angstrom resolution 01.01.2008 Project funding (Div. I-III)

Abstract

Our major long-term goal is to decipher the detailed structural mechanisms how forces might switch the functional states of proteins that are part of integrin junctions connecting the extracellular matrix (ECM) with actin filaments (Figure 1). Since no experimental techniques are available to determine the high resolution structures of proteins as they are pulled out of equilibrium by mechanical forces, steered molecular dynamics are the only current approach to establish how mechanical force might alter the structure-function relationship of proteins. Such models are urgently needed to effectively guide experiments aimed at revealing the molecular mechanisms how cells sense and respond to mechanical forces and to create hypotheses that can be experimentally tested. New hypotheses how mechanical forces can switch the structure-function relationship of those proteins that are part of force-bearing protein networks depend on the availability of high resolution structural descriptions of intermediate states. Major advances have already been made predicting various aspects of the mechanoregulatory functions of fibronectin, the integrin head piece, as well as how talin stretching upregulates vinculin recruitment (Puklin-Faucher 2009; Saltel 2009; Hytonen 2008) and reviewed in {Vogel 2009; Vogel 2006; Vogel & Sheetz, 2006). We propose to continue developing high resolution structural models how tensile mechanical forces stretch proteins that are part of cell adhesion sites out of their equilibrium states into intermediate states. We are increasingly focusing on exploiting these high resolution structural models derived from Molecular Dynamics (MD) and Steered Molecular Dynamics (SMD) to actively guide many of our experimental approaches (Little 2009; Klotzsch 2009; Sokurenko 2008) such that we can validate computational predictions. The proteins that we study play pivotal roles in mediating cell adhesion processes, and in malfunctioning in various disease (Vogel 2009).
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