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14,105 items found (0 items not approved), displaying 51 to 60.[First/Prev] 2, 3, 4, 5, 6, 7, 8, 9 [Next/Last]

Instruments / Technical Area	Publication Details	Published
I02-Macromolecular Crystallography	3,6-diamino-4-(2-halophenyl)-2-benzoylthieno[2,3-b]pyridine-5-carbonitriles are selective inhibitors of Plasmodium falciparum Glycogen synthase kinase-3 Wiebke Fugel , Anselm Erich Oberholzer , Bernhard Gschloessl , Ron Dzikowski , Narkiss Pressburger , Lutz Preu , Laurence H. Pearl , Blandine Baratte , Morgane Ratin , Ilya Okun , Christian Doerig , Sebastian Kruggel , Thomas Lemcke , Laurent Meijer , Conrad Kunick Journal Of Medicinal Chemistry 56 (1), 264 - 275 DOI: 10.1021/jm301575n PMID: 23214499 Diamond Proposal Number(s): [8015] Show Abstract ▼ Abstract: Plasmodium falciparum is the infective agent responsible for malaria tropica. The glycogen synthase kinase-3 of the parasite (PfGSK-3) was suggested as a potential biological target for novel antimalarial drugs. Starting from hit structures identified in a high-throughput screening campaign, 3,6-diamino-4-(2-halophenyl)-2-benzoylthieno[2,3-b]pyridine-5-carbonitriles were discovered as a new class of PfGSK-3 inhibitors. Being less active on GSK-3 homologues of other species, the title compounds showed selectivity in favor of PfGSK-3. Taking into account the X-ray structure of a related molecule in complex with human GSK-3 (HsGSK-3), a model was computed for the comparison of inhibitor complexes with the plasmodial and human enzymes. It was found that subtle differences in the ATP-binding pockets are responsible for the observed PfGSK-3 vs HsGSK-3 selectivity. Representatives of the title compound class exhibited micromolar IC50 values against P. falciparum erythrocyte stage parasites. These results suggest that inhibitors of PfGSK-3 could be developed as potential antimalarial drugs.	Jan 2013
I12-JEEP: Joint Engineering, Environmental and Processing	3-Dimensional analysis of fatigue crack fields and crack growth by in situ synchrotron X-ray tomography A. Koko , S. Singh , S. Barhli , T. Connolley , N. T. Vo , T. Wigger , D. Liu , Y. Fu , J. Réthoré , J. Lechambre , J.-Y. Buffiere , T. J. Marrow International Journal Of Fatigue 170 DOI: 10.1016/j.ijfatigue.2023.107541 Diamond Proposal Number(s): [12585] Open Access Show Abstract ▼ Abstract: The propagation rate of a fatigue crack in a nodular cast iron, loaded in cyclic tension, has been studied in situ by X-ray computed tomography and digital volume correlation. The semi-elliptical crack initiated from an asymmetric corner notch and evolved to a semi-circular shape, initially with a higher growth rate towards one edge of the notch before the propagation rate along the crack front became essentially independent of po-sition. The phase congruency of the displacement field was used to measure the crack shape. The three-dimensional stress intensity factors were calculated via a linear elastic finite element model that used the displacement fields around the crack front as the boundary conditions. Closure of the crack tip region was observed. The cyclic change in the local mode I opening of the crack tip determined the local fatigue crack propaga-tion rate along the crack front.	May 2023
I03-Macromolecular Crystallography I04-1-Macromolecular Crystallography (fixed wavelength) I04-Macromolecular Crystallography	3-Fluoro-4-hydroxyprolines: Synthesis, conformational analysis and stereoselective recognition by the VHL E3 ubiquitin ligase for targeted protein degradation Andrea Testa , Xavier Lucas , Guilherme V. Castro , Kwok-Ho Chan , Jane E. Wright , Andrew C. Runcie , Morgan S. Gadd , William T. A. Harrison , Eun-Jung Ko , Daniel Fletcher , Alessio Ciulli Journal Of The American Chemical Society DOI: 10.1021/jacs.8b05807 Diamond Proposal Number(s): [10071, 14980] Open Access Show Abstract ▼ Abstract: Hydroxylation and fluorination of proline alters the pyrrolidine ring pucker and the trans:cis amide bond ratio in a stereochemistry-dependent fashion, affecting molecular recognition of proline-containing molecules by biological systems. While hydroxyprolines and fluoroprolines are common motifs in medicinal and biological chemistry, the synthesis and molecular properties of prolines containing both modifications, i.e. fluoro-hydroxyprolines, have not been described. Here we present a practical and facile synthesis of all four diastereoisomers of 3-fluoro-4-hydroxyprolines (F-Hyps), starting from readily available 4-oxo-L-proline derivatives. Small-molecule X-ray crystallography, NMR spectroscopy and quantum mechanical calculations are consistent with fluorination at C3 having negligible effects on the hydrogen bond donor capacity of the C4 hydroxyl, but inverting the natural preference of Hyp from C4-exo to C4-endo pucker. In spite of this, F-Hyps still bind to the von Hippel-Lindau (VHL) E3 ligase, which naturally recognizes C4-exo Hyp in a stereoselective fashion. Co-crystal structures and electrostatic potential calculations support and rationalize the observed preferential recognition for (3R,4S)-F-Hyp over the corresponding (3S,4S) epimer by VHL. We show that (3R,4S)-F-Hyp provides bioisosteric Hyp substitution in both hypoxia inducible factor 1 alpha (HIF-1α) substrate peptides as well as peptidomimetic ligands that form part of PROTAC (PROteolysis TArgeting Chimera) conjugates for targeted protein deg-radation. Despite a weakened affinity, Hyp substitution with (3S,4S)-F-Hyp within the PROTAC MZ1 led to Brd4-selective cellular degradation at concentrations >100-fold lower than the binary Kd for VHL. We anticipate that the disclosed chemistry of 3-fluoro-4-hydroxyprolines and their application as VHL ligands for targeted protein degradation will be of wide interest to medicinal organic chemists, chemical biologists and drug discoverers alike.	Jun 2018
I03-Macromolecular Crystallography I24-Microfocus Macromolecular Crystallography	3-Oxo-β-sultam as a sulfonylating chemotype for inhibition of serine hydrolases and activity-based protein profiling Luís A. R. Carvalho , Vanessa T. Almeida , Jose A. Brito , Kenneth M. Lum , Tânia F. Oliveira , Rita C. Guedes , Lídia M. Gonçalves , Susana D. Lucas , Benjamin F. Cravatt , Margarida Archer , Rui Moreira Acs Chemical Biology DOI: 10.1021/acschembio.0c00090 Diamond Proposal Number(s): [20161] Show Abstract ▼ Abstract: 3-Oxo-β-sultams are four-membered ring ambident electrophiles that can react with nucleophiles either at the carbonyl carbon or at the sulfonyl sulfur atoms, and that have been reported to inhibit serine hydrolases via acylation of the active-site serine residue. We have developed a panel of 3-oxo-β-sultam inhibitors and show, through crystallographic data, that they are regioselective sulfonylating electrophiles, covalently binding to the catalytic serine of human and porcine elastases through the sulfur atom. Application of 3-oxo-β-sultam-derived activity-based probes in a human proteome revealed their potential to label disease-related serine hydrolases and proteasome subunits. Activity-based protein profiling applications of 3-oxo-β-sultams should open up new opportunities to investigate these classes of enzymes in complex proteomes and expand the toolbox of available sulfur-based covalent protein modifiers in chemical biology.	Mar 2020
I12-JEEP: Joint Engineering, Environmental and Processing	3D Cellular Automata fracture model for porous graphite microstructures Yelena Vertyagina , Thomas James Marrow Nuclear Engineering And Design DOI: 10.1016/j.nucengdes.2016.10.015 Diamond Proposal Number(s): [8519, 9036] Show Abstract ▼ Abstract: Nuclear graphite has a complex porous microstructure, which depends on raw materials and manufacturing process; porosity can change with radiolytic oxidation and also in the absence of oxidation with very high neutron fluences. Porosity directly affects the fracture process and the graphite tensile strength. To understand the effects of porosity on component strength and its relation to small specimen data, microstructure sensitive models are needed that can simulate the statistics of strength of porous microstructures, also addressing size and strain gradients effects such as notches. This requires multi-scale models that capture the key microstructural features with sufficient fidelity, and also with sufficient computational economy to simulate component behaviour. To achieve this, an innovative technique to calculate the elastic stress distribution in a 3D porous solid under uniaxial or biaxial tension has been developed that uses Cellular Automata. Synthetic microstructures with arbitrary distributions of pore sizes and shapes are created that simulate realistic microstructures; a fracture algorithm simulates failure initiation and crack growth. The model calculates the tensile strength of a microstructure volume for any arbitrary failure criteria; the critical strain energy release rate is used as an example to demonstrate how porosity affects the fracture process. The presented Cellular Automata (CA) model is at least an order of magnitude more efficient than finite element methods of equivalent discretisation; CA are also scale independent and well suited for parallel computing. This would allow large volumes of representative microstructures to be simulated, with a Monte-Carlo based approach to investigate strength variability.	Jan 2016
B16-Test Beamline Detectors	3D Detectors for Synchrotron Applications David Pennicard Open Access Show Abstract ▼ Abstract: 3D detectors are a novel variety of photodiode radiation detector, invented by Parker, Kenney and Segal (1997). Instead of having n- and p-type contacts on the front and back surfaces of a silicon substrate, like a standard photodiode, they have columns of doped material passing through the thickness of the silicon. This structure means that the detector can combine a reasonable substrate thickness with a very small electrode spacing, resulting in a low depletion voltage, fast charge collection and low charge sharing. These detectors have a couple of promising applications. Their fast charge collection and low depletion voltage should make them very radiation-tolerant. So, they could be used for future particle physics experiments at the Super Large Hadron Collider (SLHC), where high levels of radiation damage are expected. Also, their low charge sharing means they could potentially improve X-ray diffraction measurements at synchrotrons such as Diamond Light Source. This would allow these experiments, for example, to determine the structures of biological molecules more accurately. However, before 3D devices can be used in practical experiments, their design and fabrication must be optimised to ensure that reliable, high-performance detectors can be produced on a reasonably large scale. The aim of this thesis is to evaluate and understand the behaviour of a variety of 3D detectors using a combination of lab tests and computer simulations. Using these results, future fabrication runs can then be re-designed to improve their performance.	Apr 2009
B16-Test Beamline Optics	3D Medipix2 detector characterization with a micro-focused X-ray beam E. N. Gimenez-navarro , J. Marchal , K. J. S. Sawhney , L. Alianelli , M. Lozano , Giulio Pellegrini , C. Fleta , V. O'shea , R. Bates , C. Parkes , A. Mac Raighne , D. Maneuski , N. Tartoni IWORID 2009- International Workshop on Radiation Imaging Detectors DOI: 10.1016/j.nima.2010.06.140 Diamond Proposal Number(s): [520] Show Abstract ▼ Abstract: Three-dimensional (3D) photodiode detectors offer advantages over standard planar photodiodes in a wide range of applications. The main advantage of these sensors for X-ray imaging is their reduced charge sharing between adjacent pixels, which could improve spatial and spectral resolution. However, a drawback of 3D sensors structures is the loss of detection efficiency due to the presence in the pixel structure of heavily doped electrode columns which are insensitive to X-ray. In this work two types of 3D silicon detectors: n-type wafer with hole collecting readout-columns (n-type) and p-type wafer with electron collecting readout-columns (p-type), bump-bounded to a Medipix2 read-out chip were characterized with a 14.5 keV micro-focused X-ray beam from a synchrotron. Measurements of the detection efficiency and the charge sharing were performed at different bias voltages and Medipix2 energy thresholds and compared with those of a standard planar silicon sensor.	Jul 2010
I22-Small angle scattering & Diffraction	3D Micro- and nanostructural analysis of connective tissue in the human optic nerve head (ONH) Hannah Jones , Nick White , Jennifer Hiller , Nicholas Terrill , Keith Meek , Craig Boote , Julie Albon The Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting	Mar 2012
I13-2-Diamond Manchester Imaging	3D Pore Structure Investigation of Albian Carbonates from Campos Basin N. Lopes Archilha , R. M. Missagia , C. Hollis , M A R Ceia , I A Lima Neto , D. Eastwood Null 76th EAGE Conference and Exhibition 2014 DOI: 10.3997/2214-4609.20141280 Diamond Proposal Number(s): [4017] Show Abstract ▼ Abstract: The pore structure of three samples from two neighbouring wells in the Campos Basin, offshore Brazil, were investigated by high resolution X-ray tomography. The samples show an inverse relationship between velocity and porosity and velocity and permeability, but there are important deviations on those trends. In order to explain this behavior, the sample pore structure was investigated using a high resolution µCT. This technique provided reliable information about 3D geometry of macropores and allowed estimation of the volume of microporosity. The analysis showed an expressive difference between the pore size of samples with different textures, but not enough information to explain differences in RQI values, suggesting that other parameters, like tortuosity, are controlling permeability. The aspect ratio (ratio between width and length) does not offer a clear control on velocity trend deviation, suggesting that small differences in rock texture or cement distribution might be in control of acoustic properties of these rocks.	Jun 2014
I20-Scanning-X-ray spectroscopy (XAS/XES)	3D Printing and its applications in spectroelectrochemistry Mateus V. Pereira , Evandro Datti , Gabriel R. Alvarenga , Bruno C. Janegitz , Juliano A. Bonacin Microchemical Journal 50 DOI: 10.1016/j.microc.2022.108083 Show Abstract ▼ Abstract: The analytical tools have given not only chemistry but science as a whole, new horizons when it comes to the comprehension of chemical phenomena. With precise information, new possibilities emerged in the identification and characterization of novel compounds and advances in several areas of chemistry. In this context, spectroelectrochemistry (SEC) combines complementary tools to that the electrochemistry techniques drive the reactions and spectroscopic methods are focused on species analysis. Thus, this strategy provides a way to monitor what is happening in situ or in operando, making it a powerful tool for the identification of intermediates of reaction, mechanistic, kinetic studies, and even quantitative analysis. However, SEC comes with a somewhat inconvenient drawback: even though it has been rising in popularity, setting up the SEC cells might be complicated for newcomers. On the other hand, 3D printing becomes interesting and, at the same time, incredibly effective technology for the user to create customized SEC cells to support any necessity. In this review, we will go over the importance of 3D printing in the design and use of spectroelectrochemical cells.	Oct 2022

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