799 research outputs found

    Changes in male rat urinary protein profile during puberty: a pilot study

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    BACKGROUND: Androgen-dependent proteins (lipocalins) circulate in blood of male rats and mice and, being small (~ 18 kDa), pass freely into glomerular filtrate. Some are salvaged in proximal nephrons but some escape in urine. Several organic molecules can bind to these proteins causing, where salvage occurs, nephropathy including malignancy in renal cortex. In urine, both free lipocalins and ligands contribute to an increasingly-recognised vital biological role in social communication between adults, especially in the dark where reliance is on smell and taste. Crystal structure of the first-characterised lipocalin of male rats, α2u-globulin, has been determined and peptide sequences for others are available, but no study of occurrence during early puberty has been made. We have followed temporal occurrence in urine of juveniles (n = 3) for non-invasive pilot study by high resolution gradient mini-gel electrophoresis, tryptic digest of excised protein bands, and LC-MS/MS of digest to identify peptide fragments and assign to specific lipocalins. Study objective refers directly to external availability for social communication but also indirectly to indicate kinetics of circulating lipocalins to which some xenobiotics may bind and constitute determinants of renal disease. RESULTS: Mini-gels revealed greater lipocalin complexity than hitherto recognised, possibly reflecting post-translational modifications. Earliest patterns comprised rat urinary protein 1, already evident in Sprague-Dawley and Wistar strains at 36 and 52 days, respectively. By 44 and 57 days major rat protein (α2u-globulin) occurred as the progressively more dominant protein, though as two forms with different electrophoretic mobility, characterised by seven peptide sequences. No significant change in urinary testosterone had occurred in Wistars when major rat protein became evident, but testosterone surged by 107 days concomitant with the marked abundance of excreted lipocalins. CONCLUSIONS: Qualitative temporal changes in the composition of excreted lipocalins early in puberty, and apparent increase in major urinary protein as two resolvable forms, should catalyse systematic non-invasive study of urinary lipocalin and testosterone dynamics from early age, to illuminate this aspect of laboratory rodent social physiology. It could also define the potential temporal onset of nephrotoxic ligand risk, applicable to young animals used as toxicological models

    On high-speed turning of a third-generation gamma titanium aluminide

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    Gamma titanium aluminides are heat-resistant intermetallic alloys predestined to be employed in components suffering from high mechanical stresses and thermal loads. These materials are regarded as difficult to cut, so this makes process adaptation essential in order to obtain high-quality and defect-free surfaces suitable for aerospace and automotive parts. In this paper, an innovative approach for longitudinal external high-speed turning of a third-generation Ti-45Al-8Nb- 0.2C-0.2B gamma titanium aluminide is presented. The experimental campaign has been executed with different process parameters, tool geometries and lubrication conditions. The results are discussed in terms of surface roughness/integrity, chip morphology, cutting forces and tool wear. Experimental evidence showed that, due to the high cutting speed, the high temperatures reached in the shear zone improve chip formation, so a crack-free surface can be obtained. Furthermore, the use of a cryogenic lubrication system has been identified in order to reduce the huge tool wear, which represents the main drawback when machining gamma titanium aluminides under the chosen process condition

    Reducing delays in the diagnosis and treatment of muscle-invasive bladder cancer using simulation modelling

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    This is the author accepted manuscript. The final version is available from SAGE Publications via the DOI in this record Objective: To develop a simulation model to identify key bottlenecks in the bladder cancer pathway at Royal Cornwall Hospital and predict the impact of potential changes to reduce these delays. Materials and methods: The diagnosis and treatment of muscle-invasive bladder cancer can suffer numerous delays, which can significantly affect patient outcomes. We developed a discrete event computer simulation model of the flow of patients through the bladder cancer pathway at the hospital, using anonymised patient records from 2014 and 2015. The changes tested in the model were for patients suspected to have muscle-invasive disease on flexible cystoscopy. Those patients were ‘fast-tracked’ to receive their transurethral resection of bladder tumour (TURBT) treatment using operating slots kept free for these patients. A staging computed tomography scan was booked in the haematuria clinic. Pathology requests were marked as 48 hour turnaround. The nurse specialist would then speak to the patient whilst they were on the ward following their TURBT to give information about their ongoing treatment and provide support. Results: The model predicted that if the changes were implemented, delays in the system could be reduced by around 5 weeks. The changes were implemented, and analysis of 3 months of the data post-implementation shows that the average time in the system was reduced by 5 weeks. The environment created by the changes in the pathway improved referral to treatment times in both muscle-invasive and non-muscle-invasive groups. Conclusion: The simulation model proved an invaluable tool for facilitating the implementation of changes. Simple changes to the pathway led to significant reductions in delays for bladder cancer patients at Royal Cornwall Hospital. Level of evidence: Not applicable for this cohort study.National Institute for Health Research (NIHR

    Surface diffusion in catalysts probed by APGSTE NMR

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    In this work we report the application of a recently developed experimental protocol using Pulsed Field Gradient (PFG) Nuclear Magnetic Resonance (NMR) techniques to simultaneously assess bulk pore and surface diffusion coefficients in liquid saturated porous catalysts. This method has been developed to study solvent effects on the diffusion of methyl ethyl ketone (MEK) in mesoporous 1 wt% Pd/Al2O3 catalyst trilobes. The selection of solvents used in this work is known to have a complex effect on reaction rates and hence catalyst performance in heterogeneous liquid phase catalysis. Here, we report the bulk pore and surface diffusion characteristics of MEK, water and isopropyl alcohol (IPA) in 1 wt% Pd/Al2O3 catalyst trilobes. The results show that the physicochemical interactions of molecules in the porous catalyst matrix are very different for the different molecules. We also find that the mobility of water appears to be affected strongest by the catalyst surface

    Assessing the use of NMR chemical shifts for prediction of VLE in non-ideal binary liquid mixtures

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    A method of estimating vapour liquid equilibrium (VLE) using NMR chemical shift data has been proposed by Xu et al. (2012). This method is based on the concept that the average local composition around each species is determined by the thermodynamics of the system, and also determines the screening of the NMR active groups within that molecule, and so their NMR chemical shifts. Xu et al.‘s method has been replicated and verified; results are confirmed to be accurate for alcohol + hydrocarbon mixtures, giving VLE predictions of comparable accuracy to the UNIFAC, generally considered the best predictive activity coefficient model available. However, for more strongly non-ideal mixtures, the method becomes less reliable, giving significantly less accurate predictions of total pressure than UNIFAC. Several causes for this are identified. The model proposed by Xu et al. (2012) is unable to fit minima or maxima in chemical shifts, which are observed experimentally in some binary mixtures. Different NMR resonances within the same molecule lead to different predictions of VLE, clearly an un-physical result. The thermodynamics of strongly non-ideal mixtures are determined by more complex interactions than a simple description of average local composition around each component in the mixtures, for example strong and directional hydrogen bonds. Different groups within the same molecule may have different local compositions in their immediate vicinity; for example in the case of alcohol + water mixtures, one would expect a clustering of water molecules around the hydroxyl group but not the aliphatic group. Hence, the concept of a simple local composition model is not valid for these more complex cases, and it is therefore not surprising that a model based on this simple concept is often not effective in predicting VLE.C. D’Agostino would like to acknowledge Wolfson College, Cambridge, for supporting his research activities.This is the accepted manuscript. The final version is available from Elsevier at http://www.sciencedirect.com/science/article/pii/S0009250914004461

    Mesoscopic structuring and dynamics of alcohol/water solutions probed by terahertz time-domain spectroscopy and pulsed field gradient nuclear magnetic resonance.

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    Terahertz and PFG-NMR techniques are used to explore transitions in the structuring of binary alcohol/water mixtures. Three critical alcohol mole fractions (x1, x2, x3) are identified: methanol (10, 30, 70 mol %), ethanol (7, 15, 60 mol %), 1-propanol (2, 10, 50 mol %), and 2-propanol (2, 10, 50 mol %). Above compositions of x1 no isolated alcohol molecules exist, and below x1 the formation of large hydration shells around the hydrophobic moieties of the alcohol is favored. The maximum number of water molecules, N0, in the hydration shell surrounding a single alcohol molecule increases with the length of the carbon chain of the alcohol. At x2 the greatest nonideality of the liquid structure exists with the formation of extended hydrogen bonded networks between alcohol and water molecules. The terahertz data show the maximum absorption relative to that predicted for an ideal mixture at that composition, while the PFG-NMR data exhibit a minimum in the alkyl chain self-diffusivity at x2, showing that the alcohol has reached a minimum in diffusion when this extended alcohol-water network has reached the highest degree of structuring. At x3 an equivalence of the alkyl and alcohol hydroxyl diffusion coefficients is determined by PFG-NMR, suggesting that the molecular mobility of the alcohol molecules becomes independent of that of the water molecules.This is the final published version. It's also available from the Journal of Physical Chemistry B here: http://pubs.acs.org/doi/abs/10.1021/jp502799x
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