Abingdon Community Hospital

) can be achieved in pseudo prospective approach. Bromodomains are epigenetic mark readers that recognize acetylation motifs and regulate gene transcription, and are currently being investigated as therapeutic targets for cancer and inflammation. The unprecedented accuracy offers the exciting prospect that the binding free energy of drug-like compounds can be predicted for pharmacologically relevant targets.

The ‘immortal’ ring-opening polymerization (iROP) of pentadecalactone (PDL), catalysed by magnesium 2,6-di-<italic>tert</italic>-butyl-4-methylphenoxide (Mg(BHT)₂(THF)₂) under non-inert conditions is reported for the first time.

This review covers developments in and applications of XRF techniques such as EDXRF, WDXRF, TXRF, XRF microscopy using technologies such as synchrotron sources, X-ray optics, X-ray tubes and detectors in laboratory, mobile and hand-held systems.

Understanding of the complex electrochemical, transport, and phase-change phenomena in Li-S cells requires experimental characterization in tandem with mechanistic modeling. However, existing Li-S models currently contradict some key features of experimental findings, particularly the evolution of cell resistance during discharge. We demonstrate that, by introducing a concentration-dependent electrolyte conductivity, the correct trends in voltage drop due to electrolyte resistance and activation overpotentials are retrieved. In addition, we reveal the existence of an often overlooked potential drop mechanism in the low voltage-plateau which originates from the limited rate of Li2S precipitation.

This review covers developments in and applications of XRF techniques such as EDXRF, WDXRF, TXRF, XRF microscopy using technologies such as synchrotron sources, X-ray optics, X-ray tubes and detectors in laboratory, mobile and hand-held systems.

Langerhans cell histiocytosis (LCH) remains a poorly understood disorder with heterogeneous clinical presentations characterized by focal or disseminated lesions that contain excessive CD1a+ langerin+ cells with dendritic cell features known as "LCH cells." Two of the major questions investigated over the past century have been (i) the origin of LCH cells and (ii) whether LCH is primarily an immune dysregulatory disorder or a neoplasm. Current opinion is that LCH cells are likely to arise from hematopoietic precursor cells, although the stage of derailment and site of transformation remain unclear and may vary in patients with different extent of disease. Over the years, evidence has provided the view that LCH is a neoplasm. The demonstration of clonality of LCH cells, insufficient evidence alone for neoplasia, is now bolstered by finding driver somatic mutations in BRAF in up to 55% of patients with LCH, and activation of the RAS-RAF-MEK-ERK (where MEK and ERK are mitogen-activated protein kinase and extracellular signal-regulated kinase, respectively) pathway in nearly 100% of patients with LCH. Herein, we review the evidence that recurrent genetic abnormalities characterized by activating oncogenic mutations should satisfy prerequisites for LCH to be called a neoplasm. As a consequence, recurrent episodes of LCH should be considered relapsed disease rather than disease reactivation. Mapping the complete genetic landscape of this intriguing disease will provide additional support for the conclusion that LCH is a neoplasm and is likely to provide more potential opportunities for molecularly targeted therapies.

This study presents the application of X-ray diffraction computed tomography for the first time to analyze the crystal dimensions of LiNi0.33Mn0.33Co0.33O2 electrodes cycled to 4.2 and 4.7 V in full cells with graphite as negative electrodes at 1 μm spatial resolution to determine the change in unit cell dimensions as a result of electrochemical cycling. The nature of the technique permits the spatial localization of the diffraction information in 3D and mapping of heterogeneities from the electrode to the particle level. An overall decrease of 0.4% and 0.6% was observed for the unit cell volume after 100 cycles for the electrodes cycled to 4.2 and 4.7 V. Additionally, focused ion beam-scanning electron microscope cross-sections indicate extensive particle cracking as a function of upper cut-off voltage, further confirming that severe cycling stresses exacerbate degradation. Finally, the technique facilitates the detection of parts of the electrode that have inhomogeneous lattice parameters that deviate from the bulk of the sample, further highlighting the effectiveness of the technique as a diagnostic tool, bridging the gap between crystal structure and electrochemical performance.

conversion. Under operating conditions, the active components, present in the form of a Na-W-O-Mn molten state, are highly mobile and volatile. By varying the parameters of the calcination protocol, it was shown that these molten components can be partially stabilised, resulting in a catalyst with lower activity (due to loss of surface area) but higher stability even for long duration OCM reaction experiments.

This 2019 review covers developments in and applications of XRF techniques such as EDXRF, WDXRF, TXRF, XRF microscopy using technologies such as synchrotron sources, X-ray optics, X-ray tubes and detectors in laboratory, mobile and hand-held systems.

The use of synthetic stimulants, including designer cathinones, remains a significant concern worldwide. Thus, the detection and identification of synthetic cathinones in biological matrices is of paramount importance for clinical and forensic laboratories. In this study, distribution of mephedrone and its metabolites was investigated in fingerprints. Following a controlled human mephedrone administration (100 mg nasally insufflated), two mass spectrometry-based methods for fingerprint analysis have been evaluated. The samples deposited on triangular pieces of chromatography paper were directly analysed under ambient conditions by paper spray-mass spectrometry (PS-MS) while those deposited on glass cover slips were extracted and analysed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The LC-MS/MS method was 5-6 times more sensitive than PS-MS but required sample preparation and longer analysis time. Mephedrone was detected in 62% and in 38% of all post-administration samples analysed by LC-MS/MS and PS-MS, respectively. Nor-mephedrone was the only metabolite detected in 3.8% of all samples analysed by LC-MS/MS. A large inter- and intra-subject variation was observed for mephedrone which may be due to several factors, such as the applied finger pressure, angle and duration of contact with the deposition surface and inability to control the 'amount' of collected fingerprint deposits. Until these limitations are addressed, we suggest that the sole use of fingerprints can be a useful diagnostic tool in qualitative rather than quantitative analysis, and requires a confirmatory analysis in a different biological matrix.

A new asymmetric conjugate addition method was developed for β-substituted cyclopentenones to form quaternary centres using alkylzirconocene nucleophiles giving up to 97% yield and 92% ee. Key to the reaction's success was the design of suitable phosphoramidite ligands which was aided by a linear quantitative structure-selectivity relationship (QSSR). QSSR models were created from the ligand screening data (a total of 36 ligands) which revealed important electronic and steric requirements and led to the synthesis of more enantioselective ligands. DFT calculations of competing transition structures enable the interpretation of the electronic and steric terms present in the QSSR models.

This review covers developments in and applications of XRF techniques such as EDXRF, WDXRF, TXRF, XRF microscopy using technologies such as synchrotron sources, X-ray optics, X-ray tubes and detectors in laboratory, mobile and hand-held systems.

This review covers developments in and applications of XRF techniques such as EDXRF, WDXRF, TXRF, XRF microscopy using technologies such as synchrotron sources, X-ray optics, X-ray tubes and detectors in laboratory, mobile and hand-held systems.

Multi-block copolymers offer a plethora of exciting properties, easily tuned by modulating parameters such as monomer composition, block length, block number and dispersity.

The story of the discovery of the bis-benzimidazole derivative SMT19969, which is currently in clinical trials against the pathogen<italic>Clostridium difficile</italic>.

The microscopic mechanism of the H₂ adsorption of two Mg-MOF-74 isoreticular frameworks, one with a benzenedicarboxylate linker and the other with a dihydroxyfumarate linker, were studied on the basis of density functional theory (DFT) method.

Excess free energies, enthalpies and entropies of water in protein binding sites were computed via classical simulations and Grid Cell Theory (GCT) analyses for three pairs of congeneric ligands in complex with the proteins scytalone dehydratase, p38α MAP kinase and EGFR kinase respectively. Comparative analysis is of interest since the binding modes for each ligand pair differ in the displacement of one binding site water molecule, but significant variations in relative binding affinities are observed. Protocols that vary in their use of restraints on protein and ligand atoms were compared to determine the influence of protein-ligand flexibility on computed water structure and energetics, and to assess protocols for routine analyses of protein-ligand complexes. The GCT-derived binding affinities correctly reproduce experimental trends, but the magnitude of the predicted changes in binding affinities is exaggerated with respect to results from a previous Monte Carlo Free Energy Perturbation study. Breakdown of the GCT water free energies into enthalpic and entropic components indicates that enthalpy changes dominate the observed variations in energetics. In EGFR kinase GCT analyses revealed that replacement of a pyrimidine by a cyanopyridine perturbs water energetics up three hydration shells away from the ligand.

The surface of many Old Master paintings has been affected by the appearance of whitish lead-rich deposits, which are often difficult to fully characterise, thereby hindering conservation. A paint micro-sample from Rembrandt's Homer was imaged using X-ray Diffraction Computed Tomography (XRD-CT) in order to understand the evolving solid-state Pb chemistry from the painting surface and beneath. The surface crust was identified as a complex mixture of lead sulfates. From the S : Pb ratios throughout the paint layer, we can conclude that S is from an external source in the form of SO2, and that the nature of Pb-SO4 product is dependent on the degree of diffusion/absorption of SO2 into the paint layers.

Transmission Raman spectroscopy (TRS) is a recently introduced analytical technique to pharmaceutical analysis permitting volumetric sampling by non-destructive means. Here we demonstrate experimentally, for the first time, the enhanced speed of quantification of pharmaceutical tablets by an order of magnitude compared with conventional TRS. This is achieved using an enhancing element, "photon diode", avoiding the loss of laser photons at laser coupling interface. The proof-of-concept experiments were performed on a complex mixture consisting of 5 components (3 APIs and 2 excipients) with nominal concentrations ranging between 0.4 and 89%. Acquisition times as short as 0.01 s were reached with satisfactory quantification accuracy for all the sample components. Results suggest that even faster sampling speeds would be achievable for components with stronger Raman scattering cross sections or with higher laser powers. This major improvement in speed of volumetric analysis enables high throughput deployment of TRS for in line quality control applications within the batch or continuous manufacturing process and facilitating non-destructive analysis of large fractions.

Synchrotron-based X-ray diffraction micro-probes allow us to identify and map the distribution of<italic>in situ</italic>formed crystalline lead–sulfur compounds in historical paintings.