229 research outputs found

    Conformational Entropy as a Means to Control the Behavior of Poly(diketoenamine) Vitrimers In and Out of Equilibrium.

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    Control of equilibrium and non-equilibrium thermomechanical behavior of poly(diketoenamine) vitrimers is shown by incorporating linear polymer segments varying in molecular weight (MW) and conformational degrees of freedom into the dynamic covalent network. While increasing MW of linear segments yields a lower storage modulus at the rubbery plateau after softening above the glass transition (Tg ), both Tg and the characteristic time of stress relaxation are independently governed by the conformational entropy of the embodied linear segments. Activation energies for bond exchange in the solid state are lower for networks incorporating flexible chains; the network topology freezing temperature decreases with increasing MW of flexible linear segments but increases with increasing MW of stiff segments. Vitrimer reconfigurability is therefore influenced not only by the energetics of bond exchange for a given network density, but also the entropy of polymer chains within the network

    Spatial distribution of clinical computer systems in primary care in England in 2016 and implications for primary care electronic medical record databases: a cross-sectional population study.

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    OBJECTIVES: UK primary care databases (PCDs) are used by researchers worldwide to inform clinical practice. These databases have been primarily tied to single clinical computer systems, but little is known about the adoption of these systems by primary care practices or their geographical representativeness. We explore the spatial distribution of clinical computing systems and discuss the implications for the longevity and regional representativeness of these resources. DESIGN: Cross-sectional study. SETTING: English primary care clinical computer systems. PARTICIPANTS: 7526 general practices in August 2016. METHODS: Spatial mapping of family practices in England in 2016 by clinical computer system at two geographical levels, the lower Clinical Commissioning Group (CCG, 209 units) and the higher National Health Service regions (14 units). Data for practices included numbers of doctors, nurses and patients, and area deprivation. RESULTS: Of 7526 practices, Egton Medical Information Systems (EMIS) was used in 4199 (56%), SystmOne in 2552 (34%) and Vision in 636 (9%). Great regional variability was observed for all systems, with EMIS having a stronger presence in the West of England, London and the South; SystmOne in the East and some regions in the South; and Vision in London, the South, Greater Manchester and Birmingham. CONCLUSIONS: PCDs based on single clinical computer systems are geographically clustered in England. For example, Clinical Practice Research Datalink and The Health Improvement Network, the most popular primary care databases in terms of research outputs, are based on the Vision clinical computer system, used by <10% of practices and heavily concentrated in three major conurbations and the South. Researchers need to be aware of the analytical challenges posed by clustering, and barriers to accessing alternative PCDs need to be removed

    The secretion inhibitor Exo2 perturbs trafficking of Shiga toxin between endosomes and the trans-Golgi network

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    The small-molecule inhibitor Exo2 {4-hydroxy-3-methoxy-(5,6,7,8-tetrahydrol[1]benzothieno[2,3-d]pyrimidin-4-yl)hydraz-one benzaldehyde} has been reported to disrupt the Golgi apparatus completely and to stimulate Golgi–ER (endoplasmic reticulum) fusion in mammalian cells, akin to the well-characterized fungal toxin BFA (brefeldin A). It has also been reported that Exo2 does not affect the integrity of the TGN (trans-Golgi network), or the direct retrograde trafficking of the glycolipid-binding cholera toxin from the TGN to the ER lumen. We have examined the effects of BFA and Exo2, and found that both compounds are indistinguishable in their inhibition of anterograde transport and that both reagents significantly disrupt the morphology of the TGN in HeLa and in BS-C-1 cells. However, Exo2, unlike BFA, does not induce tubulation and merging of the TGN and endosomal compartments. Furthermore, and in contrast with its effects on cholera toxin, Exo2 significantly perturbs the delivery of Shiga toxin to the ER. Together, these results suggest that the likely target(s) of Exo2 operate at the level of the TGN, the Golgi and a subset of early endosomes, and thus Exo2 provides a more selective tool than BFA for examining membrane trafficking in mammalian cells
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