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Statistical processing of Flash X-ray Imaging of protein complexes
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics.ORCID iD: 0000-0002-1171-6683
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Description
Abstract [en]

Flash X-ray Imaging (FXI) at X-ray Free Electron Lasers (XFELs) is a promising technique that permits the investigation of the 3D structure of molecules without the need for crystallization, by diffracting on single individual sample particles.

In the past few years, some success has been achieved by using FXI on quite large biological complexes (40 nm-1 μm in diameter size). Still, the desired dream-goal of imaging a single individual of a molecule or a protein complex (<15 nm in diameter size) has not been reached yet. The main issue that prevented us from a complete success has been the low signal strength, almost comparable to background noise. That is particularly true for experiments performed at the Coherent X-ray Imaging (CXI) instrument at the Linac Coherent Light Source (LCLS).

In this thesis, we provide a brief review of the CXI instrument (focusing on experiments there performed) and present a statistical method to deal with low signal-to-noise ratios. We take into account a variety of biological particles, showing the benefits of estimating a background model from sample data and using that for processing said data. Moreover, we present the results of some computer simulations in order to explore the limits and potentials of the proposed approach.

Last, we show another method (named COACS) that, being fed with the previous findings from the background model, helps obtaining clearer results in the phase retrieval problem.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2019. , p. 88
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1764
Keywords [en]
X-ray, XFEL, single particle, hit-finder, statistical hit-finder, single protein, protein complex, RNA polymerase II, FEL, free-electron laser, FXI, Flash X-ray Imaging, CXI, CSPAD, x-ray imaging, COACS
National Category
Biological Sciences Physical Sciences
Research subject
Physics with specialization in Biophysics
Identifiers
URN: urn:nbn:se:uu:diva-372987ISBN: 978-91-513-0554-7 (print)OAI: oai:DiVA.org:uu-372987DiVA, id: diva2:1278413
Public defence
2019-03-06, C8:301, BMC, Husargatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2019-02-08 Created: 2019-01-14 Last updated: 2019-02-08
List of papers
1. Artifact reduction in the CSPAD detectors used for LCLS experiments
Open this publication in new window or tab >>Artifact reduction in the CSPAD detectors used for LCLS experiments
2017 (English)In: Journal of Synchrotron Radiation, ISSN 0909-0495, E-ISSN 1600-5775, Vol. 24, p. 1092-1097Article in journal (Refereed) Published
National Category
Biophysics
Identifiers
urn:nbn:se:uu:diva-328543 (URN)10.1107/S160057751701058X (DOI)000408902800025 ()28862634 (PubMedID)
Projects
eSSENCE
Available from: 2017-07-18 Created: 2017-08-25 Last updated: 2019-01-14Bibliographically approved
2. A statistical approach to detect protein complexes at X-ray free electron laser facilities
Open this publication in new window or tab >>A statistical approach to detect protein complexes at X-ray free electron laser facilities
Show others...
2018 (English)In: Communications Physics, E-ISSN 2399-3650, Vol. 1, p. 92:1-11, article id 92Article in journal (Refereed) Published
National Category
Biophysics
Identifiers
urn:nbn:se:uu:diva-369876 (URN)10.1038/s42005-018-0092-6 (DOI)000452676300003 ()
Projects
eSSENCE
Available from: 2018-12-07 Created: 2018-12-17 Last updated: 2019-01-17Bibliographically approved
3. Using convex optimization of autocorrelation with constrained support and windowing for improved phase retrieval accuracy
Open this publication in new window or tab >>Using convex optimization of autocorrelation with constrained support and windowing for improved phase retrieval accuracy
2018 (English)In: Optics Express, ISSN 1094-4087, E-ISSN 1094-4087, Vol. 26, p. 24422-24443Article in journal (Refereed) Published
National Category
Computational Mathematics Biophysics
Identifiers
urn:nbn:se:uu:diva-360037 (URN)10.1364/OE.26.024422 (DOI)000444705000012 ()30469561 (PubMedID)
Projects
eSSENCE
Available from: 2018-09-05 Created: 2018-09-09 Last updated: 2019-01-14Bibliographically approved

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