I12-JEEP: Joint Engineering, Environmental and Processing
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Ilaria
Quaratesi
,
Ioan
Călinescu
,
Petre
Chipurici
,
Elisa-Gabriela
Dumbravă
,
Andrei
Cucos
,
Mohamed Yassine
Zaki
,
Pellegrino
La Manna
,
Adrian
Bercea
,
Miruna Silvia
Stan
,
Stefan
Michalik
,
Chloe
Pearce
,
Marianne
Odlyha
,
Genoveva
Burca
,
Elena
Badea
Diamond Proposal Number(s):
[35634]
Open Access
Abstract: This study presents an ultrasound-assisted synthesis of β-cyclodextrin/hydroxyapatite composites to be used as green and safe auxiliaries in the tanning process. A combination of spectroscopic and non-spectroscopic techniques such as DLS (dynamic light scattering), ZP (zeta potential), XRD (X-ray diffraction), SEM (scanning electron microscopy) and ATR-FTIR (attenuated total reflectance-Fourier transform infrared spectroscopy) were used to thoroughly characterize the eight composites obtained by varying the ultrasound process parameters. While not cytotoxic, all composites had strong antibacterial action against Brevibacterium lines, Staphylococcus aureus, Escherichia coli, and Staphylococcus epidermis. All composites underwent lab-scale tanning tests, but only those exhibiting the most suitable set of tanning abilities underwent pilot-scale testing. The composites' interaction with the collagen matrix was assessed by micro-DSC (micro-differential scanning calorimetry), TG/DTG/DTA (thermal analysis), 1H unilateral NMR (proton nuclear magnetic resonance), ATR-FTIR, in-situ temperature synchrotron-based XRD and standard tests (UNI EN ISO 3380: 2015, UNI EN ISO 2589: 2016, UNI EN ISO 105- B02:2014). Thermal stability, dye penetration, thickness, colour fastness, surface appearance and microbiological protection were all improved for the leather treated with a small amount of composite added to the wet finish float. These findings demonstrate the benefits of β-cyclodextrin/hydroxyapatite composites as safe and sustainable tanning additives.
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Apr 2025
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Krios V-Titan Krios V at Diamond
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Bin
Yang
,
Durga
Devalla
,
Silvia
Sonzini
,
Mikael
Boberg
,
Sashi
Gopaul
,
Monika
Sundqvist
,
Iain
Grant
,
Christopher
Jones
,
Stephanie
Brookes
,
Cindy
Weidauer
,
Eleonora
Paladino
,
Najet
Mahmoudi
,
Jason
Van Rooyen
,
Ana Gomes
Dos Santos
,
Johanna
Laru
,
Andy
Campbell
,
Lutz
Jermutus
,
Annette
Bak
Diamond Proposal Number(s):
[31098, 37220]
Abstract: Cotadutide (Cota) is a lipidated dual GLP-1 and Glucagon receptor agonist that was investigated for the treatment of various metabolic diseases, it is designed for once daily subcutaneous (SC) administration. Invasive daily injections can result in poor patient compliance with chronic disease, and here, we demonstrate an innovative strategy of encapsulating reversible cota self-assembled fibers within an in-situ forming depot of low molecular weight poly(lactic-co-glycolic) acid (LWPLGA) for sustained delivery GLP-1 and Glucagon receptor agonist with controlled burst release. This could be a suitable alternative to other sustained delivery strategies for fibrillating peptides. We investigated a range of cationic ions (Na+, Ca2+, Zn2+) and studied their influence on the secondary structure, morphology and the monomer release profile of cota fibers. Fibers forming hierarchy structures such as twisted filament and ribbons with beta sheet secondary structure resulted in better controlled burst. The subcutaneous administration of Ca2+ fiber/LWPLGA depot formulation in rats resulted in 60-fold reduction in maximum concentration (Cmax) compared with cota immediate release (IR) SC formulation and a prolonged plasma exposure over a month with plasma half-life extended from the 10 h observed with the cota daily formulation to 100 h. This extended-release formulation also maintains smaller peak and trough fluctuation within therapeutic window, and PK modelling of repeated dose indicates this formulation could enable a possible dose frequency of 14 days in rat with assumed therapeutic concentration (ratios of the maximum concentration and the trough concentration) Cmax/Ctrough window. This new long-acting injectable (LAI) method could open the door to transforming short-life peptides with sub-optimal half-life into candidates for weekly or even monthly dosing regimens, potentially leading to novel drug products with increased patient comfort.
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Apr 2025
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I19-Small Molecule Single Crystal Diffraction
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Diamond Proposal Number(s):
[30375]
Abstract: We present a combined experimental and density functional theory study that characterizes the charge and spin density in NiX2(3,5-lutidine)4 (X = Cl, Br and I). In this material, magnetic exchange interactions occur via Ni2+–halide⋯halide–Ni2+ pathways, forming one-dimensional chains. We find evidence for weak halide⋯halide covalency in the iodine system, which is greatly reduced when X = Br and is absent for X = Cl; this is consistent with the reported `switching-on' of magnetic exchange in the larger-halide cases. Our results are benchmarked against density functional theory calculations on [NiHF2(pyrazine)2]SbF6, in which the primary magnetic exchange is mediated by F–H–F bridging ligands. This comparison indicates that, despite the largely depleted charge density found at the centre of halide⋯halide bonds, these through-space interactions can support strong magnetic exchange gated by weak covalency and enhanced by significant electron density overlapping that of the transition metal centres.
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Apr 2025
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I12-JEEP: Joint Engineering, Environmental and Processing
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Diamond Proposal Number(s):
[26767]
Open Access
Abstract: Lithium ion batteries are pivotal for clean energy storage and mitigating climate change. In this study, we employ operando synchrotron X-ray computed tomography to investigate the dynamic evolution of battery cathode microstructure. We focus on tracking changes in porosity and pore size distribution at the microscale and cathode thickness at the macroscale during the lithiation and delithiation processes within a commercially configured battery. Image quality was enhanced using both conventional image processing methods and a Super-Resolution Convolutional Neural Network (SRCNN) model. Our findings revealed a slight increase in the cathode solid volume fraction and specific surface area as the battery transitioned from its pristine state to fully lithiated, followed by a reduction during delithiation. This behavior was attributed to the expansion of the cathode material and phase transitions during lithiation, which split larger pores into smaller ones, as evidenced by the increase in surface area. Cathode thickness also exhibited expansion during lithiation and contraction during delithiation. These results offer valuable insights into the structural changes that contribute to battery aging, helping researchers better understand how these different parameters change over time. This understanding is crucial for designing more durable and sustainable batteries in the future, both in terms of specific design and material selection, to enhance resistance during charge and discharge cycles to improve performance and longevity.
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Apr 2025
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I14-Hard X-ray Nanoprobe
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F.
Dal Molin
,
D.
Hunt
,
A.
Dewar
,
S.
Lozach
,
C.
Phillips
,
B.
Thomas
,
L.
Warford
,
J. E.
Parker
,
J.
Walker
,
M.
Chocholek
,
D. M.
Paterson
,
H.
Woodward-Rowe
,
N.
Hicks
Diamond Proposal Number(s):
[35954]
Open Access
Abstract: Although oil and gas (O&G) derived produced waters and drill cuttings are known to contain enhanced levels of naturally occurring radium-228 (228Ra) and radium-226 (226Ra), most relevant ecological impact assessments have excluded radiological hazards and focus on other important contaminants, such as hydrocarbons and metals. Also, due to restricted access to the delimiting safety zone around operational O&G platforms, the few previous radioecological risk assessment studies have been conducted using seawater samples collected far from the main discharge point and applying default dilution and transfer factors to estimate concentrations of contaminants in biota. In this case study, sediment cores were collected close to a former O&G platform, Northwest Hutton (NWH), that used to be in the UK North Sea (61.11N, 1.31E). The sediment materials were analysed by gamma spectrometry and ICP-MS to confirm the presence of particles enriched in natural radioactivity. Benthic macrofaunal assemblages in the surrounding seabed were also characterised and one of the dominant species was selected for additional nano-hard X-Ray Fluorescence (nano-XRF) imaging to confirm the exposure pathways and refine the radioecological risk assessment using the ERICA tool. This novel approach for estimating dose rates was found to be less conservative than more traditional approaches using the ERICA default concentration ratio for 228Ra and 226Ra. The dose rate estimations were confirmed to be significantly lower than the ERICA screening level of 10μGy/h, in agreement with findings from previous studies.
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Mar 2025
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B21-High Throughput SAXS
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Saishree S.
Iyer
,
Fangrui
Chen
,
Funso E.
Ogunmolu
,
Shoeib
Moradi
,
Vladimir A.
Volkov
,
Emma J.
Van Grinsven
,
Chris
Van Hoorn
,
Jingchao
Wu
,
Nemo
Andrea
,
Shasha
Hua
,
Kai
Jiang
,
Ioannis
Vakonakis
,
Mia
Potočnjak
,
Franz
Herzog
,
Benoît
Gigant
,
Nikita
Gudimchuk
,
Kelly E.
Stecker
,
Marileen
Dogterom
,
Michel O.
Steinmetz
,
Anna
Akhmanova
Diamond Proposal Number(s):
[21035]
Open Access
Abstract: Centrioles are microtubule-based organelles required for the formation of centrosomes and cilia. Centriolar microtubules, unlike their cytosolic counterparts, are stable and grow very slowly, but the underlying mechanisms are poorly understood. Here, we reconstituted in vitro the interplay between the proteins that cap distal centriole ends and control their elongation: CP110, CEP97, and CPAP/SAS-4. We found that whereas CEP97 does not bind to microtubules directly, CP110 autonomously binds microtubule plus ends, blocks their growth, and inhibits depolymerization. Cryo-electron tomography revealed that CP110 associates with the luminal side of microtubule plus ends and suppresses protofilament flaring. CP110 directly interacts with CPAP, which acts as a microtubule polymerase that overcomes CP110-induced growth inhibition. Together, the two proteins impose extremely slow processive microtubule growth. Disruption of CP110–CPAP interaction in cells inhibits centriole elongation and increases incidence of centriole defects. Our findings reveal how two centriolar cap proteins with opposing activities regulate microtubule plus-end elongation and explain their antagonistic relationship during centriole formation.
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Mar 2025
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B21-High Throughput SAXS
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Diamond Proposal Number(s):
[32486]
Open Access
Abstract: Lipoic acid is a biocompatible compound with antioxidant activity that is of considerable interest in cosmetic formulations, and the disulfide group in the N-terminal ring confers redox activity. Here, we study the self-assembly and aspects of the bioactivity of a lipopeptide (peptide amphiphile) comprising the KTTKS collagen-stimulating pentapeptide sequence conjugated to an N-terminal lipoic acid chain, lipoyl-KTTKS. Using SAXS, SANS and cryo-TEM, lipoyl-KTTKS is found to form a population of curly fibrils (wormlike micelles) above a critical aggregation concentration. Upon chemical reduction, the fibrils (and β-sheet structure) are disrupted because of the breaking of the disulfide bond, which produces dihydrolipoic acid. Lipoyl-KTTKS also undergoes photo-degradation in the presence of UV radiation. Through cell assays using fibroblasts, we found that lipoyl-KTTKS has excellent cytocompatibility across a wide concentration range, stimulates collagen production, and enhances the rate of cell coverage in a simple in vitro scratch assay of ‘wound healing’. Lipoyl-KTTKS thus has several notable properties that may be useful for the development of cosmetics, cell scaffolds or tissue engineering materials.
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Mar 2025
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I03-Macromolecular Crystallography
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Diamond Proposal Number(s):
[28534]
Abstract: Objective: Along with rising resistance to antimalarials, the emergence of insecticide resistance in Anopheles mosquito species also remains a serious concern. Here, we reveal two potent compounds that show larvicidal and endectocidal activity against malaria vectors, Anopheles culicifacies and Anopheles stephensi, respectively. Methods: We investigated larvicidal activity of two inhibitors against III-instar larvae of Anopheles culicifacies. The survival and fertility of adult female Anopheles stephensi mosquitoes were assessed. Additionally, we purified recombinant prolyl-tRNA synthetase of Anopheles culicifacies and performed enzyme-based assays and structural analysis with the two inhibitors. Results: Our study reveals that the Anopheles culicifacies prolyl-tRNA synthetase (AcProRS) is potently inhibited by halofuginone (HFG) and an ATP mimetic (L95). The evaluation of larvicidal activity of HFG against Anopheles culicifacies III-instar larvae showed a dose-dependent increase in mortality. In adult female Anopheles stephensi mosquitoes, ingestion of HFG via artificial blood feeding resulted in impaired ovary development, reduced egg laying, and decreased overall survival. The potent enzymatic inhibition of AcProRS thus drives the killing of larvae. The co-crystal structure of AcProRS with inhibitors provides a structural basis for improving their potency as future larvicides. Conclusion: Our data suggest the potential for repositioning halofuginone (HFG) and pyrrolidine-based ATP-mimetics (L95) as larvicides. Targeting the vector-encoded aminoacyl-tRNA synthetases provides a new focus for developing effective agents that can control multiple mosquitoe-borne infectious diseases like malaria and dengue.
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Mar 2025
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I20-Scanning-X-ray spectroscopy (XAS/XES)
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Diamond Proposal Number(s):
[24399]
Open Access
Abstract: The catalytic conversion of C–H to C–F bonds is a critical synthetic transformation of relevance to the pharmaceutical, agrochemical, and medicinal chemical industries. When coupled with an oxidant and a fluorine donor, biomimetic Mn-porphyrins have been shown to be capable of achieving this reaction. However, the definition of the active forms of these fluorinating Mn-porphyrins remains an unsolved challenge, which limits mechanistic understanding of the process and makes it challenging to systematically design better catalytic materials. Herein, we present a combination of kinetic, spectroscopic, and theoretical studies focused on alkane fluorination over Mn-containing porphyrins. Specifically, by correlating kinetic studies with resonance Raman, UV–vis, and high-energy resolution fluorescence detected X-ray absorption spectroscopic analysis of the various states of the catalyst, we provide evidence that a 6-coordinated Mn(IV) complex with −F and −OI(F)Ar axial ligands is the active species responsible for selective fluorination via Hydrogen Atom Transfer. This active state is distinct from the Mn═O species previously proposed to be the active intermediates for alkane fluorination and oxidation.
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Mar 2025
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I03-Macromolecular Crystallography
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Open Access
Abstract: Differential scanning fluorimetry screening of the Library of Pharmacologically Active Compounds (LOPAC) identified four hits for the PRYSPRY domain of the human E3 ligase tripartite motif-containing protein 21 (TRIM21). Isothermal titration calorimetry subsequently confirmed suramin as a binder with micromolar affinity. To further investigate the binding mechanism, mouse TRIM21 was used as a structural surrogate due to its improved protein stability and high sequence similarity to the human counterpart. A crystal structure of the complex refined at 1.3 Å resolution revealed a unique binding mode, providing new avenues for targeting TRIM21 and for the development of proteolysis-targeting chimeras (PROTACs).
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Mar 2025
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