I03-Macromolecular Crystallography
I04-Macromolecular Crystallography
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Diamond Proposal Number(s):
[25402, 33658]
Open Access
Abstract: Environment-sensitive fluorescent probes are indispensable tools for studying biological systems and advancing drug discovery. This study reports the development of 4-sulfamoyl-7-aminobenzoxadiazole (SBD)-based fluorescent probes for the allosteric site of the liver isoform of pyruvate kinase (PKL). By integrating SBD moieties into known activator scaffolds, such as mitapivat and diarylsulfonamide (DASA) ligands, probes for indicator displacement assays were designed to quantify ligand interactions in the allosteric site. Compound 4a displayed dose-dependent fluorescence enhancement in response to PKL binding and was used in a competitive binding assay with unlabelled ligands: mitapivat, TEPP-46, DASA-58 and reported activator 21. Structure–activity relationship (SAR) analysis revealed key structural features influencing activity and fluorescence sensitivity. The probes report selectively on the allosteric site ligands as the binding was not affected by natural ligands, such as ADP, fructose-1,6-bisphosphate (FBP), phosphoenolpyruvate (PEP), and phenylalanine. These findings provide a practical framework for detecting allosteric ligand engagement in PKL and expand the repertoire of molecular tools for advancing PKL-targeted therapies.
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Nov 2025
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DIAD-Dual Imaging and Diffraction Beamline
I12-JEEP: Joint Engineering, Environmental and Processing
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Franck P.
Vidal
,
Shaghayegh
Afshari
,
Sharif
Ahmed
,
Alberto
Albiol
,
Francisco
Albiol
,
Éric
Béchet
,
Alberto Corbí
Bellot
,
Stefan
Bosse
,
Simon
Burkhard
,
Younes
Chahid
,
Cheng-Ying
Chou
,
Robert
Culver
,
Pascal
Desbarats
,
Lewis
Dixon
,
Johan
Friemann
,
Amin
Garbout
,
Marcos
García-Lorenzo
,
Jean-François
Giovannelli
,
Ross
Hanna
,
Clémentine
Hatton
,
Audrey
Henry
,
Graham
Kelly
,
Christophe
Leblanc
,
Alberto
Leonardi
,
Jean Michel
Létang
,
Harry
Lipscomb
,
Tristan
Manchester
,
Bas
Meere
,
Claire
Michelet
,
Simon
Middleburgh
,
Radu P.
Mihail
,
Iwan
Mitchell
,
Liam
Perera
,
Martí
Puig
,
Malek
Racy
,
Ali
Rouwane
,
Hervé
Seznec
,
Aaron
Sújar
,
Jenna
Tugwell-Allsup
,
Pierre-Frédéric
Villard
Diamond Proposal Number(s):
[29820]
Open Access
Abstract: gVirtualXray (gVXR) is an open-source framework that relies on the Beer–Lambert law to simulate X-ray images in real time on a graphics processor unit (GPU) using triangular meshes. A wide range of programming languages is supported (C/C++, Python, R, Ruby, Tcl, C#, Java, and GNU Octave). Simulations generated with gVXR have been benchmarked with clinically realistic phantoms (i.e. complex structures and materials) using Monte Carlo (MC) simulations, real radiographs and real digitally reconstructed radiographs (DRRs), and X-ray computed tomography (XCT). It has been used in a wide range of applications, including real-time medical simulators, proposing a new densitometric radiographic modality in clinical imaging, studying noise removal techniques in fluoroscopy, teaching particle physics and X-ray imaging to undergraduate students in engineering, and XCT to masters students, predicting image quality and artifacts in material science, etc. gVXR has also been used to produce a high number of realistic simulated images in optimisation problems and to train machine learning algorithms. This paper presents a comprehensive review of such applications of gVXR.
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Nov 2025
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B21-High Throughput SAXS
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Diamond Proposal Number(s):
[31850]
Open Access
Abstract: To ensure safety, pharmaceuticals are rigorously tested for lipopolysaccharide (LPS) contamination, as this can trigger severe immune reactions in patients. Low Endotoxin Recovery (LER), describing the masking of spiked LPS controls in Limulus Amebocyte Lysate (LAL) assays, has been associated with the presence of chelating agents and surfactants in pharmaceutical formulations. The addition of excipients, such as Mg2+, have shown the ability to mitigate the effects of LER, however, inconsistencies in various studies regarding the influence of the excipients on LPS aggregate characteristics and LER occurrence hinder a clear understanding of the mechanisms underlying LER. In this study, dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS) were employed to systematically assess the impact of chelating agents, surfactants, and divalent cations on the size and shape of LPS aggregates across various formulations. Our results indicate that surfactant-only formulations generally reduce LPS aggregate size, whereas chelating agent-only formulations do not. Notably, the smallest aggregates were observed when both chelating agents and surfactants were present, with the extent of size reduction being specific to the particular excipients used. Additionally, Mg2+ generally inhibited the excipients’ capacity to decrease aggregate size, most effectively in phosphate-containing samples. Despite these variations in size, the overall aggregate shape remained largely unchanged in all formulations. These findings suggest that LPS aggregate size or shape does not distinguish formulations causing LER; instead, factors such as the characteristics of the LPS aggregate surface in different formulations should be explored in the future.
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Nov 2025
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I16-Materials and Magnetism
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Diamond Proposal Number(s):
[34820]
Open Access
Abstract: We present results of an experimental study on single crystals of a 5d
double perovskite Ba2CaReO6. Magnetization measurements reveal a weak splitting between zero-field-cooled and field-cooled protocols below 12 K. At magnetic fields above 1 T the splitting is absent and the magnetic susceptibility is featureless. A detailed specific heat study in a wide temperature range and comprising different heat pulses did not reveal any indication of a thermodynamic phase transition. At low temperatures we do observe specific heat deviating from a phonon background, leading to a total electronic entropy release of
. Resonant and non-resonant x-ray diffraction of characteristic Bragg peaks indicates a significant presence of disorder, potentially related to random tilts and rotations of rigid ReO6 octahedra.
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Nov 2025
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B21-High Throughput SAXS
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Diamond Proposal Number(s):
[36130]
Open Access
Abstract: The initiation of allergic responses critically depends on the recognition of an allergenic epitope by the paratope of IgE antibodies. While previous structural studies have focused on recombinant fragments or engineered forms of IgE, the structure of full-length IgE in its native state remains poorly understood. In this study, we investigate the conformational changes of a native murine IgE (2F5), both in its free form and upon binding to the Hevea brasiliensis allergen profilin (Hev b 8). Small-angle X-ray scattering (SAXS) data reveal that unbound IgE adopts an extended conformation with open Fab arms. However, when it binds to profilin, it transitions to a more compact arrangement characterized by closer proximity of the arms. Molecular dynamics (MD) simulations of the Fab region further identified conformational rearrangements upon allergen binding, including a twisting motion and partial disruption of interactions between the naturally paired heavy and light chains. These findings indicate that there may be allosteric communication between Fab and Fc regions, even in the absence of a hinge region, which is not present in IgE. Overall, this study provides valuable insights into the dynamic structural properties of native IgE and enhances our understanding of the molecular mechanisms underlying allergen recognition.
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Nov 2025
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I13-2-Diamond Manchester Imaging
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Diamond Proposal Number(s):
[22053, 31714]
Abstract: Accurate predictions of the size and morphology of microstructural features, including defects such as porosity, are essential for predicting the performance of engineering components. Although several multiscale approaches exist in the literature, including direct simulations and volume-averaged models, their predictions are limited due to large computational times and relatively low accuracy. This work utilises transfer learning to link the macroscopic field variable distributions to the mesoscale, in order to estimate sub-grid microstructural defects. Specifically, the model parameters are corrected using experimental measurements of sub-grid scale defects. The proposed methodology is illustrated for predicting porosity in an aluminium alloy automotive component produced using high pressure die casting. The model uses a physics-based localised porosity model for combined gas and shrinkage porosity to train an artificial neural network. This trained machine learning model is subsequently re-trained using macroscale field variables and experimental X-ray microtomography porosity measurements from industrial component made using different process conditions. An unseen region of the same component is used for further testing of the performance of the model. The results show good prediction of pore size distribution and location. These results are then used to determine component fatigue life. Thus, a full process-structure-property model is established. The framework has the potential to be applied to a large class of problems involving predictions of microstructural features over entire macroscopic components.
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Nov 2025
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Sang-Kil
Son
,
Thomas M.
Baumann
,
Jacob
Pedersen
,
Laura
Budewig
,
Kai
Li
,
Hans
Ågren
,
Olle
Björneholm
,
Rebecca
Boll
,
John
Bozek
,
Carl
Caleman
,
Sebastian
Cardoch
,
Lucas M.
Cornetta
,
Alberto
De Fanis
,
Emiliano
De Santis
,
Simon
Dold
,
Gilles
Doumy
,
Ulrich
Eichmann
,
Xiaochun
Gong
,
Johan
Gråsjö
,
Alice E.
Green
,
Iyas
Ismail
,
Ludvig
Kjellsson
,
Eva
Lindroth
,
Tommaso
Mazza
,
Jacobo
Montaño
,
Terry
Mullins
,
Christian
Ott
,
Yevheniy
Ovcharenko
,
Thomas
Pfeifer
,
Maria
Novella Piancastelli
,
Ralph
Püttner
,
Nils
Rennhack
,
Nina
Rohringer
,
Cecilia
Sanchez-Hanke
,
Conny
Såthe
,
Philipp
Schmidt
,
Björn
Senfftleben
,
Marc
Simon
,
Nicuşor
Tîmneanu
,
Moto
Togawa
,
Kiyoshi
Ueda
,
Sergey
Usenko
,
Hans Jakob
Wörner
,
Weiqing
Xu
,
Zhong
Yin
,
Linda
Young
,
Joseph
Nordgren
,
Marcus
Agåker
,
Johan
Söderström
,
Sonia
Corian
,
Michael
Meyer
,
Robin
Santra
,
Jan-Erik
Rubensson
Open Access
Abstract: We report resonant inelastic x-ray scattering (RIXS) spectra of neon atoms interacting with intense x-ray pulses generated using an x-ray free-electron laser (XFEL). We find that an unexpected peak emerges near the 𝐾𝛼 line of Ne, which does not coincide with any physical resonances of neon ions. We perform theoretical calculations based on a quantum-state-resolved rate-equation approach with x-ray-induced processes including possible resonant excitations. Our dynamics simulations demonstrate that a sequence of multiple resonant photoabsorption events are involved and the interplay of those multiple resonances in combination with the relatively large spectral bandwidth of XFEL radiation leads to the emergent resonance-like structure at a position where no resonances exist. Our finding offers critical guidance for future applications of high-intensity RIXS at XFEL facilities.
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Nov 2025
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I03-Macromolecular Crystallography
I04-Macromolecular Crystallography
I24-Microfocus Macromolecular Crystallography
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Abstract: Biocatalytic hydrogen atom transfer (HAT) holds the potential to help address some long-standing challenges in organic synthesis. Although several families of enzymes rely on cysteine to perform HAT, these enzymes are rather impractical for synthetic purposes. To circumvent possible side reactions associated with cysteinyl radicals, we report herein artificial hydrogen atom transferases (AHATases) with an abiological thiophenol cofactor, capitalizing on biotin–streptavidin technology. Chemogenetic optimization afforded an AHATase with good reactivity and high enantioselectivity (er up to 93:7) for the photoinduced radical hydroamination of alkenes. Crystal structures suggest that aromatic-sulfur interactions are key contributing factors to cofactor anchoring and enantioinduction. Mechanistic studies support H atom abstraction and donation processes, both of which are catalyzed by the AHATase. Our work highlights the synthetic potential of thiol-based biocatalytic HAT and expands the repertoire of HAT biocatalysis.
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Nov 2025
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B18-Core EXAFS
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Diamond Proposal Number(s):
[32381]
Abstract: This study aimed at determining Ni and Co leaching kinetics from a New Caledonian laterite in an acidic medium (H2SO4 pH 1.5) and in a reductive environment (addition of SO32− or Fe(II)) at 46 °C. The mineralogical study revealed that Co was mainly carried by Mn oxyhydroxides in the limonite sample. Conversely, Ni was hosted by both Fe and Mn oxyhydroxides. In the presence of a reductive reagent, Mn oxyhydroxides dissolved rapidly compared to goethite, the main Fe oxyhydroxide in the sample. Co, Mn and Ni reductive leaching yields reached 79 %, 83 % and 9 % respectively after 2 days. Based on these results, a Mn oxides concentrate was produced in order to efficiently leach Co while limiting Fe oxyhydroxide dissolution. This concentrate resulted from a combination of particle size and gravity separation steps. The volume/mass of sample was drastically decreased since the mass of the final sample was only 3.3 % of the initial one. Co content increased from 0.16 wt% in the limonite to 2.3 wt% in the concentrate, representing an enrichment factor of 13.8 and recovery yield of 60 %. Co, Mn and Ni leaching yields reached 87 %, 95 % and 80 % respectively in the Mn oxides concentrate leaching experiment. The difference in Ni behaviour was consistent with the mineralogical composition: Ni was mainly carried by the goethite in the laterite, while it was hosted mainly by the Mn oxyhydroxides in the Mn oxides concentrate. This study gives a proof of concept for the development a robust pre-concentration process to recover Co.
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Nov 2025
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I12-JEEP: Joint Engineering, Environmental and Processing
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Emily C.
Giles
,
Abbey
Jarvis
,
Pierrot S.
Attidekou
,
Kieran
O'Regan
,
Rosie
Madge
,
Alexander T.
Sargent
,
Beatrice
Browning
,
Anton
Zorin
,
Roberto
Sommerville
,
Alex J.
Green
,
Stefan
Michalik
,
Philip A.
Chater
,
Daniel
Reed
,
Emma
Kendrick
,
Laura L.
Driscoll
,
Peter
Slater
,
Phoebe K.
Allan
,
Paul
Anderson
,
Luke
Sweeney
Open Access
Abstract: Understanding the degradation of large format lithium-ion pouch cells – critical for electric vehicle applications – is vital to extend their lifetime and allow potential second-life application. Here, the impact on capacity fade and material degradation in two end-of-life cells, which were additionally subjected to accelerated aging to mimic extended use in second-life applications, were examined using powder synchrotron X-ray diffraction, Raman spectroscopy and electrochemical impedance spectroscopy, complemented by detailed post mortem analyses. The dominant mechanism of capacity loss under these conditions was found to be lithium inventory depletion, driven by processes such as electrolyte decomposition, lithium plating and solid electrolyte interphase growth. Structural changes in the graphite anode, including amorphization and reduced active material, were more pronounced under severe overcharging conditions. The blended cathode showed lithium inventory loss in both phases, but 92–94% capacity recovery was observed on subsequent cycling in half cells vs Li, illustrating its robustness, with little structural degradation observed. The finding that electrolyte degradation/loss in these cells was a more critical contributor to cell degradation toward the knee-point than electrode active material degradation/loss indicates that increasing – or replenishing – the electrolyte content could be a strategy to extend the usable life of such cells.
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Nov 2025
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