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  1. Book ; Online ; E-Book: Dynamics and Kinetics in Structural Biology

    Moffat, Keith / Lattman, Eaton E.

    Unravelling Function Through Time-Resolved Structural Analysis

    2024  

    Author's details Keith Moffat and Eaton E. Lattman
    Keywords Molecular dynamics ; Biomolecules/Structure
    Subject code 541.394
    Language English
    Size 1 online resource (281 pages)
    Edition First edition.
    Publisher John Wiley & Sons Ltd
    Publishing place Hoboken, NJ
    Document type Book ; Online ; E-Book
    Remark Zugriff für angemeldete ZB MED-Nutzerinnen und -Nutzer
    ISBN 1-119-69630-5 ; 1-119-69635-6 ; 9781119696285 ; 978-1-119-69630-8 ; 978-1-119-69635-3 ; 1119696283
    Database ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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  2. Article ; Online: Laue diffraction and time-resolved crystallography: a personal history.

    Moffat, Keith

    Philosophical transactions. Series A, Mathematical, physical, and engineering sciences

    2019  Volume 377, Issue 2147, Page(s) 20180243

    Abstract: A personal, historical view is presented of Laue X-ray diffraction and its application to time-resolved studies of dynamic processes, largely in light-sensitive biological systems. In Laue diffraction, a stationary crystal is illuminated by a ... ...

    Abstract A personal, historical view is presented of Laue X-ray diffraction and its application to time-resolved studies of dynamic processes, largely in light-sensitive biological systems. In Laue diffraction, a stationary crystal is illuminated by a polychromatic X-ray source. Laue diffraction has inherent complications largely absent in monochromatic diffraction, and consequently fell into disuse for quantitative structure determination. However, the advent of naturally polychromatic, intense, pulsed storage ring X-ray sources in the 1970s led to re-examination at Daresbury and elsewhere of its underlying principles. Laue diffraction has been successfully applied at storage ring sources to time-resolved, pump-probe crystallographic studies, whose exposure time and time resolution were progressively reduced from minutes to seconds, milliseconds, nanoseconds and 100 ps. Most recently, hard X-ray free electron laser sources have been used to generate narrow bandpass Laue diffraction patterns. The femtosecond X-ray pulses from such sources are completely destructive, generate only one diffraction pattern per tiny crystal and have unusual properties. However, they too are being applied to time-resolved crystallography to explore, for example, isomerization and rapid tertiary structural changes on the chemical, femtosecond timescale. This article is part of the theme issue 'Fifty years of synchrotron science: achievements and opportunities'.
    Language English
    Publishing date 2019-04-27
    Publishing country England
    Document type Journal Article
    ZDB-ID 208381-4
    ISSN 1471-2962 ; 0080-4614 ; 0264-3820 ; 0264-3952 ; 1364-503X
    ISSN (online) 1471-2962
    ISSN 0080-4614 ; 0264-3820 ; 0264-3952 ; 1364-503X
    DOI 10.1098/rsta.2018.0243
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Femtosecond structural photobiology.

    Moffat, Keith

    Science (New York, N.Y.)

    2018  Volume 361, Issue 6398, Page(s) 127–128

    MeSH term(s) Bacteriorhodopsins ; Photobiology ; Radiography ; Retina ; X-Rays
    Chemical Substances Bacteriorhodopsins (53026-44-1)
    Language English
    Publishing date 2018-07-11
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.aau3200
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Small crystals, fast dynamics and noisy data are indeed beautiful.

    Moffat, Keith

    IUCrJ

    2017  Volume 4, Issue Pt 4, Page(s) 303–305

    Abstract: Structural biology at hard X-ray free-electron lasers is evolving rapidly beyond the experimental styles long established at storage ring sources. The comprehensive review by John Spence [ ...

    Abstract Structural biology at hard X-ray free-electron lasers is evolving rapidly beyond the experimental styles long established at storage ring sources. The comprehensive review by John Spence [
    Language English
    Publishing date 2017-06-30
    Publishing country England
    Document type Journal Article
    ZDB-ID 2754953-7
    ISSN 2052-2525
    ISSN 2052-2525
    DOI 10.1107/S2052252517009472
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Lung clearance index (LCI

    Urquhart, Don S / Dowle, Heather / Moffat, Kellie / Forster, Jody / Cunningham, Steve / Macleod, Kenneth A

    Pediatric pulmonology

    2024  Volume 59, Issue 5, Page(s) 1449–1453

    Abstract: Background: Elexacaftor in combination with Tezacaftor and Ivacaftor (ETI) became licensed in the United Kingdom in early 2022 for children aged 6-11 years with cystic fibrosis (CF) and an eligible mutation. Many in this age group have excellent prior ... ...

    Abstract Background: Elexacaftor in combination with Tezacaftor and Ivacaftor (ETI) became licensed in the United Kingdom in early 2022 for children aged 6-11 years with cystic fibrosis (CF) and an eligible mutation. Many in this age group have excellent prior lung health making quantitative measurement of benefit challenging. Clinical trials purport that lung clearance index (LCI
    Objectives: This study aimed to understand the clinical utility of LCI
    Patient selection/methods: Baseline anthropometric data were collected along with spirometry (forced expiratory volume in 1 s [FEV
    Results: Twelve children were studied (seven male, mean age 9.5 years at baseline). Our study population had a mean (SD) LCI
    Conclusions: Real-world changes in LCI
    MeSH term(s) Humans ; Cystic Fibrosis/drug therapy ; Cystic Fibrosis/physiopathology ; Child ; Male ; Female ; Aminophenols/therapeutic use ; Quinolones/therapeutic use ; Indoles/therapeutic use ; Forced Expiratory Volume/drug effects ; Benzodioxoles/therapeutic use ; Drug Combinations ; Pyridines/therapeutic use ; Pyrazoles/therapeutic use ; Lung/physiopathology ; Lung/drug effects ; Pyrroles/therapeutic use ; Vital Capacity/drug effects ; Spirometry ; Chloride Channel Agonists/therapeutic use ; Pyrrolidines
    Chemical Substances Aminophenols ; Quinolones ; Indoles ; Benzodioxoles ; Drug Combinations ; Pyridines ; Pyrazoles ; Pyrroles ; elexacaftor (RRN67GMB0V) ; Chloride Channel Agonists ; ivacaftor (1Y740ILL1Z) ; Pyrrolidines
    Language English
    Publishing date 2024-02-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 632784-9
    ISSN 1099-0496 ; 8755-6863
    ISSN (online) 1099-0496
    ISSN 8755-6863
    DOI 10.1002/ppul.26938
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Structural biology is solved - now what?

    Ourmazd, Abbas / Moffat, Keith / Lattman, Eaton Edward

    Nature methods

    2022  Volume 19, Issue 1, Page(s) 24–26

    MeSH term(s) Algorithms ; Computational Biology/methods ; Computational Biology/trends ; Databases, Protein ; Protein Conformation ; Proteins/chemistry ; Proteins/metabolism ; Ribosomes/chemistry ; Ribosomes/metabolism
    Chemical Substances Proteins
    Language English
    Publishing date 2022-01-11
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2169522-2
    ISSN 1548-7105 ; 1548-7091
    ISSN (online) 1548-7105
    ISSN 1548-7091
    DOI 10.1038/s41592-021-01357-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: 66 Design of light-sensitive molecules for time-resolved crystallography and optogenetics.

    Moffat, Keith

    Journal of biomolecular structure & dynamics

    2015  Volume 33 Suppl 1, Page(s) 43

    Language English
    Publishing date 2015
    Publishing country England
    Document type Journal Article
    ZDB-ID 49157-3
    ISSN 1538-0254 ; 0739-1102
    ISSN (online) 1538-0254
    ISSN 0739-1102
    DOI 10.1080/07391102.2015.1032683
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Book ; Online: Power Grid Parameter Estimation Without Phase Measurements

    Brouillon, Jean-Sébastien / Moffat, Keith / Dörfler, Florian / Ferrari-trecate, Giancarlo

    Theory and Empirical Validation

    2024  

    Abstract: Reliable integration and operation of renewable distributed energy resources requires accurate distribution grid models. However, obtaining precise models is often prohibitively expensive, given their large scale and the ongoing nature of grid operations. ...

    Abstract Reliable integration and operation of renewable distributed energy resources requires accurate distribution grid models. However, obtaining precise models is often prohibitively expensive, given their large scale and the ongoing nature of grid operations. To address this challenge, considerable efforts have been devoted to harnessing abundant consumption data for automatic model inference. The primary result of the paper is that, while the impedance of a line or a network can be estimated without synchronized phase angle measurements in a consistent way, the admittance cannot. Furthermore, a detailed statistical analysis is presented, quantifying the expected estimation errors of four prevalent admittance estimation methods. Such errors constitute fundamental model inference limitations that cannot be resolved with more data. These findings are empirically validated using synthetic data and real measurements from the town of Walenstadt, Switzerland, confirming the theory. The results contribute to our understanding of grid estimation limitations and uncertainties, offering guidance for both practitioners and researchers in the pursuit of more reliable and cost-effective solutions.
    Keywords Electrical Engineering and Systems Science - Systems and Control ; Statistics - Applications
    Subject code 310
    Publishing date 2024-01-18
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Time-resolved crystallography and protein design: signalling photoreceptors and optogenetics.

    Moffat, Keith

    Philosophical transactions of the Royal Society of London. Series B, Biological sciences

    2014  Volume 369, Issue 1647, Page(s) 20130568

    Abstract: Time-resolved X-ray crystallography and solution scattering have been successfully conducted on proteins on time-scales down to around 100 ps, set by the duration of the hard X-ray pulses emitted by synchrotron sources. The advent of hard X-ray free- ... ...

    Abstract Time-resolved X-ray crystallography and solution scattering have been successfully conducted on proteins on time-scales down to around 100 ps, set by the duration of the hard X-ray pulses emitted by synchrotron sources. The advent of hard X-ray free-electron lasers (FELs), which emit extremely intense, very brief, coherent X-ray pulses, opens the exciting possibility of time-resolved experiments with femtosecond time resolution on macromolecular structure, in both single crystals and solution. The X-ray pulses emitted by an FEL differ greatly in many properties from those emitted by a synchrotron, in ways that at first glance make time-resolved measurements of X-ray scattering with the required accuracy extremely challenging. This opens up several questions which I consider in this brief overview. Are there likely to be chemically and biologically interesting structural changes to be revealed on the femtosecond time-scale? How shall time-resolved experiments best be designed and conducted to exploit the properties of FELs and overcome challenges that they pose? To date, fast time-resolved reactions have been initiated by a brief laser pulse, which obviously requires that the system under study be light-sensitive. Although this is true for proteins of the visual system and for signalling photoreceptors, it is not naturally the case for most interesting biological systems. To generate more biological targets for time-resolved study, can this limitation be overcome by optogenetic, chemical or other means?
    MeSH term(s) Crystallography, X-Ray/methods ; Electrons ; Lasers ; Optogenetics/methods ; Protein Engineering/methods ; Proteins/chemistry ; Proteins/ultrastructure ; Synchrotrons ; X-Ray Diffraction/methods
    Chemical Substances Proteins
    Language English
    Publishing date 2014-06-09
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 208382-6
    ISSN 1471-2970 ; 0080-4622 ; 0264-3839 ; 0962-8436
    ISSN (online) 1471-2970
    ISSN 0080-4622 ; 0264-3839 ; 0962-8436
    DOI 10.1098/rstb.2013.0568
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: CRISPR-Mediated Gene Activation (CRISPRa) of pp38/pp24 Orchestrates Events Triggering Lytic Infection in Marek's Disease Virus-Transformed Cell Lines.

    Roy, Poornima / Moffat, Katy / Nair, Venugopal / Yao, Yongxiu

    Microorganisms

    2021  Volume 9, Issue 8

    Abstract: Marek's disease (MD) is an immunosuppressive and highly contagious lymphoproliferative disease caused by Marek's disease virus (MDV) in poultry. Lymphoblastoid cell lines (LCLs) generated ex vivo from MD lymphomas are considered excellent models to study ...

    Abstract Marek's disease (MD) is an immunosuppressive and highly contagious lymphoproliferative disease caused by Marek's disease virus (MDV) in poultry. Lymphoblastoid cell lines (LCLs) generated ex vivo from MD lymphomas are considered excellent models to study virus-host molecular interactions. LCLs mostly have latently infected MDV genome, but many of them also have varying populations of lytically-infected cells, thus making them very suitable to examine the molecular events associated with the switch from latent to lytic infection. MDV-encoded phosphoprotein 38 (pp38) is readily detectable in lytically-infected LCLs and hence considered as a biomarker for lytic infection. Whilst previous studies have suggested that pp38 is essential for the early cytolytic infection of B-cells, its role in the switch from latent to lytic infection of LCLs is still unclear. pp24, another phosphorylated protein in the same protein complex, shares the same promoter and N-terminal 65 amino acids as pp38. In this study we employed CRISPR activation (CRISPRa) technology for targeted activation of pp38/pp24 in LCLs to investigate their role in inducing lytic infection. Our results show that enforced expression of pp38/pp24 through CRISPRa induces orchestrated upregulation of other MDV genes including ICP4, gB, Meq and pp14 as well as differential expression of host genes thereby facilitating lytic infection. Our results also show that pp38/pp24 expression induces the lytic switch through inhibiting apoptosis.
    Language English
    Publishing date 2021-08-08
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2720891-6
    ISSN 2076-2607
    ISSN 2076-2607
    DOI 10.3390/microorganisms9081681
    Database MEDical Literature Analysis and Retrieval System OnLINE

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