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11,353 items found (0 items not approved), displaying 1 to 10.[First/Prev] 1, 2, 3, 4, 5, 6, 7, 8 [Next/Last]

Instruments / Technical Area	Publication Details	Published
I12-JEEP: Joint Engineering, Environmental and Processing	An operando spatially resolved study of alkaline battery discharge using a novel hyperspectral detector and X-ray tomography Thomas Connolley , Oxana V. Magdysyuk , Stefan Michalik , Phoebe K. Allan , Manuela Klaus , Paul H. Kamm , Francisco Garcia-moreno , Jennifer A. Nelson , Matthew Veale , Matthew Wilson Journal Of Applied Crystallography 53 DOI: 10.1107/S1600576720012078 Diamond Proposal Number(s): [16771] Open Access Show Abstract ▼ Abstract: An experimental technique is described for the collection of time-resolved X-ray diffraction information from a complete commercial battery cell during discharging or charging cycles. The technique uses an 80 × 80 pixel 2D energy-discriminating detector in a pinhole camera geometry which can be used with a polychromatic X-ray source. The concept was proved in a synchrotron X-ray study of commercial alkaline Zn–MnO2 AA size cells. Importantly, no modification of the cell was required. The technique enabled spatial and temporal changes to be observed with a time resolution of 20 min (5 min of data collection with a 15 min wait between scans). Chemical changes in the cell determined from diffraction information were correlated with complementary X-ray tomography scans performed on similar cells from the same batch. The clearest results were for the spatial and temporal changes in the Zn anode. Spatially, there was a sequential transformation of Zn to ZnO in the direction from the separator towards the current collector. Temporally, it was possible to track the transformation of Zn to ZnO during the discharge and follow the corresponding changes in the cathode.	Dec 2020
I03-Macromolecular Crystallography	Improving metabolic stability and removing aldehyde oxidase liability in a 5-azaquinazoline series of IRAK4 inhibitors Sébastien L. Degorce , Anna Aagaard , Rana Anjum , Iain A. Cumming , Coura R. Diène , Charlene Fallan , Tony Johnson , Karl-johan Leuchowius , Alexandra L. Orton , Stuart Pearson , Graeme R. Robb , Alan Rosen , Graeme B. Scarfe , James S. Scott , James M. Smith , Oliver R. Steward , Ina Terstiege , Michael J. Tucker , Paul Turner , Stephen D. Wilkinson , Gail L. Wrigley , Yafeng Xue Bioorganic & Medicinal Chemistry 28 DOI: 10.1016/j.bmc.2020.115815 Show Abstract ▼ Abstract: In this article, we report our efforts towards improving in vitro human clearance in a series of 5-azaquinazolines through a series of C4 truncations and C2 expansions. Extensive DMPK studies enabled us to tackle high Aldehyde Oxidase (AO) metabolism and unexpected discrepancies in human hepatocyte and liver microsomal intrinsic clearance. Our efforts culminated with the discovery of 5-azaquinazoline 35, which also displayed exquisite selectivity for IRAK4, and showed synergistic in vitro activity against MyD88/CD79 double mutant ABC-DLBCL in combination with the covalent BTK inhibitor acalabrutinib.	Dec 2020
I19-Small Molecule Single Crystal Diffraction	High-pressure sapphire capillary cell for synchrotron single-crystal X-ray diffraction measurements to 1500 bar Charles J. Mcmonagle , David R. Allan , Mark R. Warren , Konstantin V. Kamenev , Gemma F. Turner , Stephen A. Moggach Journal Of Applied Crystallography 53 DOI: 10.1107/S1600576720013710 Diamond Proposal Number(s): [15190, 14164] Show Abstract ▼ Abstract: A new sapphire capillary pressure cell for single-crystal X-ray diffraction measurements at moderate pressures (200−1500 bar; 1 bar = 100 kPa) has been developed and optimized for use on beamline I19 at Diamond Light Source. The three-component cell permits optical centring of the crystal and in situ pressure modification to a precision of 1 bar. Compression of hexamethylenetetramine and its deuterated analogue to 1000 bar was performed, showcasing the accuracy and precision of the measurements, and highlighting evidence of a geometric isotope effect.	Dec 2020
	Discovery of allosteric binding sites by crystallographic fragment screening Tobias Krojer , James S. Fraser , Frank Von Delft Current Opinion In Structural Biology 65, 209 - 216 DOI: 10.1016/j.sbi.2020.08.004 Show Abstract ▼ Abstract: Understanding allosteric regulation of proteins is fundamental to our study of protein structure and function. Moreover, allosteric binding pockets have become a major target of drug discovery efforts in recent years. However, even though the function of almost every protein can be influenced by allostery, it remains a challenge to discover, rationalise and validate putative allosteric binding pockets. This review examines how the discovery and analysis of putative allosteric binding sites have been influenced by the availability of centralised facilities for crystallographic fragment screening, along with newly developed computational methods for modelling low occupancy features. We discuss the experimental parameters required for success, and how new methods could influence the field in the future. Finally, we reflect on the general problem of how to translate these findings into actual ligand development programs.	Dec 2020
I18-Microfocus Spectroscopy	Adsorption of rare earth elements in regolith-hosted clay deposits Anouk M. Borst , Martin P. Smith , Adrian Finch , Guillaume Estrade , Cristina Villanova-de-benavent , Peter Nason , Eva Marquis , Nicola J. Horsburgh , Kathryn M. Goodenough , Cheng Xu , Jindřich Kynický , Kalotina Geraki Nature Communications 11 DOI: 10.1038/s41467-020-17801-5 Diamond Proposal Number(s): [14793, 15903] Open Access Show Abstract ▼ Abstract: Global resources of heavy Rare Earth Elements (REE) are dominantly sourced from Chinese regolith-hosted ion-adsorption deposits in which the REE are inferred to be weakly adsorbed onto clay minerals. Similar deposits elsewhere might provide alternative supply for these high-tech metals, but the adsorption mechanisms remain unclear and the adsorbed state of REE to clays has never been demonstrated in situ. This study compares the mineralogy and speciation of REE in economic weathering profiles from China to prospective regoliths developed on peralkaline rocks from Madagascar. We use synchrotron X-ray absorption spectroscopy to study the distribution and local bonding environment of Y and Nd, as proxies for heavy and light REE, in the deposits. Our results show that REE are truly adsorbed as easily leachable 8- to 9-coordinated outer-sphere hydrated complexes, dominantly onto kaolinite. Hence, at the atomic level, the Malagasy clays are genuine mineralogical analogues to those currently exploited in China.	Dec 2020
B18-Core EXAFS	The formation of stoichiometric uranium brannerite (UTi2O6) glass-ceramic composites from the component oxides in a one-pot synthesis Malin C. Dixon Wilkins , Martin C. Stennett , Ewan Maddrell , Neil C. Hyatt Journal Of Nuclear Materials 542 DOI: 10.1016/j.jnucmat.2020.152516 Diamond Proposal Number(s): [17243] Open Access Show Abstract ▼ Abstract: Brannerite glass-ceramic composites have been suggested as suitable wasteform materials for high-actinide content wastes, but the formation of glass-ceramic composites containing stoichiometric uranium brannerite (UTi2O6) has not been well-studied. Uranium brannerite glass-ceramic composites were synthesised at by a one-pot cold-press and sinter route from the component oxides. As a comparison, two further samples were produced using an alkoxide-nitrate route. A range of compositions with varying molar ratios of uranium and titanium oxides (from 1:2 to 1:3.20) were synthesised, with a range of different heat treatments (1200 °C for 12–48 h, and 1250 °C for 12 h). All compositions were analysed by X-ray diffraction, scanning electron microscopy, energy dispersive X-ray spectroscopy, and X-ray near-edge spectroscopy, and found to contain UTi2O6 as the majority crystalline phase forming within a glass matrix of nominal stoichiometry Na2AlBSi6O16. In compositions with UO2:TiO2 ratios of 1:2 and 1:2.28, particles of UO2 were observed in the glass matrix, likely due to dissolution of TiO2 in the glass phase; this was prevented by the addition of excess TiO2. This work demonstrates the suitability of this system to produce highly durable wasteforms with excellent actinide waste loading, even with a simple one-pot process. Some grains of brannerite consist of a UO2 particle encapsulated in a shell of UTi2O6, suggesting that brannerite crystallises around particles of UO2 until either the UO2 is fully depleted, or the kinetic barrier becomes too large for further diffusion to occur. We propose that the formation of brannerite within glass-ceramic composites at lower temperatures than that for pure ceramic brannerite is caused by an increase in the rate of diffusion of the reactants within the glass.	Dec 2020
I04-1-Macromolecular Crystallography (fixed wavelength)	Synthesis, biological evaluation, in silico modeling and crystallization of novel small monocationic molecules with potent antiproliferative activity by dual mechanism Lucía Serran Aguilera , Elena Mariotto , Gianluca Rubbini , Francisco Fermín Castro Navas , Carmen Marco , María Paz Carrasco-jiménez , Marco Ballarotto , Antonio Macchiarulo , Ramon Hurtado-guerrero , Giampietro Viola , Luisa Carlota Lopez-cara European Journal Of Medicinal Chemistry 207 DOI: 10.1016/j.ejmech.2020.112797 Diamond Proposal Number(s): [8035] Show Abstract ▼ Abstract: Seeking for new anticancer drugs with strong antiproliferative activity and simple molecular structure, we designed a novel series of compounds based on our previous reported pharmacophore model composed of five moieties. Antiproliferative assays on four tumoral cell lines and evaluation of Human Choline Kinase CKα1 enzymatic activity was performed for these compounds. Among tested molecules, those ones with biphenyl spacer showed betters enzymatic and antiproliferative activities (n-v). Docking and crystallization studies validate the hypothesis and confirm the results. The most active compound (t) induces a significant arrest of the cell cycle in G0/G1 phase that ultimately lead to apoptosis, following the mitochondrial pathway, as demonstrated for other choline kinase inhibitors. However additional assays reveal that the inhibition of choline uptake could also be involved in the antiproliferative outcome of this class of compounds.	Dec 2020
	Recent results in time resolved serial femtosecond crystallography at XFELs Allen M. Orville Current Opinion In Structural Biology 65, 193 - 208 DOI: 10.1016/j.sbi.2020.08.011 Open Access Show Abstract ▼ Abstract: Time-resolved serial femtosecond crystallography (tr-SFX) methods exploit slurries of crystalline samples that range in size from hundreds of nanometers to a few tens of micrometers, at near-physiological temperature and pressure, to generate atomic resolution models and probe authentic function with the same experiment. ‘Dynamic structural biology’ is often used to encompass the research philosophy and techniques. Reaction cycles for tr-SFX studies are initiated by photons or ligand addition/mixing strategies, wherein the latter are potentially generalizable across enzymology. Thus, dynamic structural biology often creates stop-motion molecular movies of macromolecular function. In metal-dependent systems, complementary spectroscopic information can also be collected from the same samples and X-ray pulses, which provides even more detailed mechanistic insights. These types of experimental data also complement quantum mechanical and classical dynamics numerical calculations. Correlated structural-functional results will yield more detailed mechanistic insights and will likely translate into better drugs and treatments impacting human health, and better catalysis for clean energy and agriculture.	Dec 2020
B23-Circular Dichroism	Allosteric inhibition of human exonuclease1 (hExo1) through a novel extended β-sheet conformation Aminu Argungu Umar , Susan Liddell , Rohanah Hussain , Giuliano Siligardi , Gemma Harris , Stephen Carr , Karishma Asiani , Darren M. Gowers , Mark Odell , David J. Scott Biochimica Et Biophysica Acta (bba) - General Subjects 1864 DOI: 10.1016/j.bbagen.2020.129730 Diamond Proposal Number(s): [15313, 14658, 14430] Show Abstract ▼ Abstract: Background: Human Exonuclease1 (hExo1) participates in the resection of DNA double-strand breaks by generating long 3′-single-stranded DNA overhangs, critical for homology-based DNA repair and activation of the ATR-dependent checkpoint. The C-terminal region is essential for modulating the activity of hExo1, containing numerous sites of post-translational modification and binding sites for partner proteins. Methods: Analytical Ultracentrifugation (AUC), Dynamic Light Scattering (DLS), Circular Dichroism (CD) spectroscopy and enzymatic assays. Results: AUC and DLS indicates the C-terminal region has a highly extended structure while CD suggest a tendency to adopt a novel left-handed β-sheet structure, together implying the C-terminus may exhibit a transient fluctuating structure that could play a role in binding partner proteins known to regulate the activity of hExo1. Interaction with 14–3-3 protein has a cooperative inhibitory effect upon DNA resection activity, which indicates an allosteric transition occurs upon binding partner proteins. Conclusions: This study has uncovered that hExo1 consist of a folded N-terminal nuclease domain and a highly extended C-terminal region which is known to interact with partner proteins that regulates the activity of hExo1. A positively cooperative mechanism of binding allows for stringent control of hExo1 activity. Such a transition would coordinate the control of hExo1 by hExo1 regulators and hence allow careful coordination of the process of DNA end resection.	Dec 2020
B16-Test Beamline Optics	Hard X-ray ptychography for optics characterization using a partially coherent synchrotron source Thomas E. J. Moxham , Aaron Parsons , Tunhe Zhou , Lucia Alianelli , Hongchang Wang , David Laundy , Vishal Dhamgaye , Oliver J. L. Fox , Kawal Sawhney , Alexander M. Korsunsky Journal Of Synchrotron Radiation 27 DOI: 10.1107/S1600577520012151 Open Access Show Abstract ▼ Abstract: Ptychography is a scanning coherent diffraction imaging technique which provides high resolution imaging and complete spatial information of the complex electric field probe and sample transmission function. Its ability to accurately determine the illumination probe has led to its use at modern synchrotrons and free-electron lasers as a wavefront-sensing technique for optics alignment, monitoring and correction. Recent developments in the ptychography reconstruction process now incorporate a modal decomposition of the illuminating probe and relax the restriction of using sources with high spatial coherence. In this article a practical implementation of hard X-ray ptychography from a partially coherent X-ray source with a large number of modes is demonstrated experimentally. A strongly diffracting Siemens star test sample is imaged using the focused beam produced by either a Fresnel zone plate or beryllium compound refractive lens. The recovered probe from each optic is back propagated in order to plot the beam caustic and determine the precise focal size and position. The power distribution of the reconstructed probe modes also allows the quantification of the beams coherence and is compared with the values predicted by a Gaussian–Schell model and the optics exit intensity.	Nov 2020

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