94 research outputs found

    Is graphene on copper doped?

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    Angle-resolved photoemission spectroscopy (ARPES) and X-ray photoemission spectroscopy have been used to characterise epitaxially ordered graphene grown on copper foil by low-pressure chemical vapour deposition. A short vacuum anneal to 200 °C allows observation of ordered low energy electron diffraction patterns. High quality Dirac cones are measured in ARPES with the Dirac point at the Fermi level (undoped graphene). Annealing above 300 °C produces n-type doping in the graphene with up to 350 meV shift in Fermi level, and opens a band gap of around 100 meV. Dirac cone dispersion for graphene on Cu foil after vacuum anneals (left: 200 °C, undoped; right: 500 °C, n-doped). Centre: low energy electron diffraction from graphene on Cu foil after 200 °C anneal. Data from Antares (SOLEIL)

    Amyloid beta dimers/trimers potently induce cofilin-actin rods that are inhibited by maintaining cofilin-phosphorylation

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    <p>Abstract</p> <p>Background</p> <p>Previously we reported 1 μM synthetic human amyloid beta<sub>1-42 </sub>oligomers induced cofilin dephosphorylation (activation) and formation of cofilin-actin rods within rat hippocampal neurons primarily localized to the dentate gyrus.</p> <p>Results</p> <p>Here we demonstrate that a gel filtration fraction of 7PA2 cell-secreted SDS-stable human Aβ dimers and trimers (Aβd/t) induces maximal neuronal rod response at ~250 pM. This is 4,000-fold more active than traditionally prepared human Aβ oligomers, which contain SDS-stable trimers and tetramers, but are devoid of dimers. When incubated under tyrosine oxidizing conditions, synthetic human but not rodent Aβ<sub>1-42</sub>, the latter lacking tyrosine, acquires a marked increase (620 fold for EC<sub>50</sub>) in rod-inducing activity. Gel filtration of this preparation yielded two fractions containing SDS-stable dimers, trimers and tetramers. One, eluting at a similar volume to 7PA2 Aβd/t, had maximum activity at ~5 nM, whereas the other, eluting at the void volume (high-n state), lacked rod inducing activity at the same concentration. Fractions from 7PA2 medium containing Aβ monomers are not active, suggesting oxidized SDS-stable Aβ<sub>1-42 </sub>dimers in a low-n state are the most active rod-inducing species. Aβd/t-induced rods are predominantly localized to the dentate gyrus and mossy fiber tract, reach significance over controls within 2 h of treatment, and are reversible, disappearing by 24 h after Aβd/t washout. Overexpression of cofilin phosphatases increase rod formation when expressed alone and exacerbate rod formation when coupled with Aβd/t, whereas overexpression of a cofilin kinase inhibits Aβd/t-induced rod formation.</p> <p>Conclusions</p> <p>Together these data support a mechanism by which Aβd/t alters the actin cytoskeleton via effects on cofilin in neurons critical to learning and memory.</p

    Patients’ evaluations of patient safety in English general practices: a cross-sectional study

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    Background: The frequency and nature of safety problems and harm in general practices has previously relied on information supplied by health professionals, and scarce attention has been paid to experiences of patients. Aim: To examine patient-reported experiences and outcomes of patient safety in Primary Care in England. Design and Setting: Cross-sectional study in 45 general practices. Method: A postal version of the Patient Reported Experiences and Outcomes of Safety in Primary Care (PREOS-PC) questionnaire was sent to a random sample of 6,736 patients. Main outcome measures included “practice activation” (what does the practice do to create a safe environment); “patient activation” (how pro-active are patients in ensuring safe healthcare delivery); “experiences of safety events” (safety errors); “outcomes of safety” (harm); and “overall perception of safety” (how safe do patients rate their practice). Results: 1,244 patients (18.4%) returned completed questionnaires. Scores were high for “practice activation” (mean (standard error) = 80.4 out of 100 (2.0)) and low for “patient activation” (26.3 out of 100 (2.6)). A substantial proportion of patients (45%) reported having experienced at least one safety problem in the previous 12 months, mostly related to appointments (33%), diagnosis (17%), patient-provider communication (15%), and coordination between providers (14%). 221 patients (23%) reported some degree of harm in the previous 12 months. The overall assessment of the level of safety of their practices was generally high (86.0 out of 100 (16.8)). Conclusion: Priority areas for patient safety improvement in general practices in England include appointments, diagnosis, communication, coordination and patient activation

    Intermittent control models of human standing: similarities and differences

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    Two architectures of intermittent control are compared and contrasted in the context of the single inverted pendulum model often used for describing standing in humans. The architectures are similar insofar as they use periods of open-loop control punctuated by switching events when crossing a switching surface to keep the system state trajectories close to trajectories leading to equilibrium. The architectures differ in two significant ways. Firstly, in one case, the open-loop control trajectory is generated by a system-matched hold, and in the other case, the open-loop control signal is zero. Secondly, prediction is used in one case but not the other. The former difference is examined in this paper. The zero control alternative leads to periodic oscillations associated with limit cycles; whereas the system-matched control alternative gives trajectories (including homoclinic orbits) which contain the equilibrium point and do not have oscillatory behaviour. Despite this difference in behaviour, it is further shown that behaviour can appear similar when either the system is perturbed by additive noise or the system-matched trajectory generation is perturbed. The purpose of the research is to come to a common approach for understanding the theoretical properties of the two alternatives with the twin aims of choosing which provides the best explanation of current experimental data (which may not, by itself, distinguish beween the two alternatives) and suggesting future experiments to distinguish between the two alternatives

    Rectal Transmission of Transmitted/Founder HIV-1 Is Efficiently Prevented by Topical 1% Tenofovir in BLT Humanized Mice

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    Rectal microbicides are being developed to prevent new HIV infections in both men and women. We focused our in vivo preclinical efficacy study on rectally-applied tenofovir. BLT humanized mice (n = 43) were rectally inoculated with either the primary isolate HIV-1(JRCSF) or the MSM-derived transmitted/founder (T/F) virus HIV-1(THRO) within 30 minutes following treatment with topical 1% tenofovir or vehicle. Under our experimental conditions, in the absence of drug treatment we observed 50% and 60% rectal transmission by HIV-1(JRCSF) and HIV-1(THRO), respectively. Topical tenofovir reduced rectal transmission to 8% (1/12; log rank p = 0.03) for HIV-1(JRCSF) and 0% (0/6; log rank p = 0.02) for HIV-1(THRO). This is the first demonstration that any human T/F HIV-1 rectally infects humanized mice and that transmission of the T/F virus can be efficiently blocked by rectally applied 1% tenofovir. These results obtained in BLT mice, along with recent ex vivo, Phase 1 trial and non-human primate reports, provide a critically important step forward in the development of tenofovir-based rectal microbicides

    Atomic-Scale Time-Resolved Imaging of Krypton Dimers, Chains and Transition to a One-Dimensional Gas

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    Single-atom dynamics of noble-gas elements have been investigated using time-resolved transmission electron microscopy (TEM), with direct observation providing for a deeper understanding of chemical bonding, reactivity, and states of matter at the nanoscale. We report on a nanoscale system consisting of endohedral fullerenes encapsulated within single-walled carbon nanotubes ((Kr@C60)@SWCNT), capable of the delivery and release of krypton atoms on-demand, via coalescence of host fullerene cages under the action of the electron beam (in situ) or heat (ex situ). The state and dynamics of Kr atoms were investigated by energy dispersive X-ray spectroscopy (EDS), electron energy loss spectroscopy (EELS), and X-ray photoelectron spectroscopy (XPS). Kr atom positions were measured precisely using aberration-corrected high-resolution TEM (AC-HRTEM), aberration-corrected scanning TEM (AC-STEM), and single-atom spectroscopic imaging (STEM-EELS). The electron beam drove the formation of 2Kr@C120 capsules, in which van der Waals Kr2 and transient covalent [Kr2]+ bonding states were identified. Thermal coalescence led to the formation of longer coalesced nested nanotubes containing more loosely bound Krn chains (n = 3–6). In some instances, delocalization of Kr atomic positions was confirmed by STEM analysis as the transition to a one-dimensional (1D) gas, as Kr atoms were constrained to only one degree of translational freedom within long, well-annealed, nested nanotubes. Such nested nanotube structures were investigated by Raman spectroscopy. This material represents a highly compressed and dimensionally constrained 1D gas stable under ambient conditions. Direct atomic-scale imaging has revealed elusive bonding states and a previously unseen 1D gaseous state of matter of this noble gas element, demonstrating TEM to be a powerful tool in the discovery of chemistry at the single-atom level

    Cytomegalovirus-Specific IL-10-Producing CD4+ T Cells Are Governed by Type-I IFN-Induced IL-27 and Promote Virus Persistence

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    CD4+ T cells support host defence against herpesviruses and other viral pathogens. We identified that CD4+ T cells from systemic and mucosal tissues of hosts infected with the β-herpesviridae human cytomegalovirus (HCMV) or murine cytomegalovirus (MCMV) express the regulatory cytokine interleukin (IL)-10. IL-10+CD4+ T cells co-expressed TH1-associated transcription factors and chemokine receptors. Mice lacking T cell-derived IL-10 elicited enhanced antiviral T cell responses and restricted MCMV persistence in salivary glands and secretion in saliva. Thus, IL-10+CD4+ T cells suppress antiviral immune responses against CMV. Expansion of this T-cell population in the periphery was promoted by IL-27 whereas mucosal IL-10+ T cell responses were ICOS-dependent. Infected Il27rα-deficient mice with reduced peripheral IL-10+CD4+ T cell accumulation displayed robust T cell responses and restricted MCMV persistence and shedding. Temporal inhibition experiments revealed that IL-27R signaling during initial infection was required for the suppression of T cell immunity and control of virus shedding during MCMV persistence. IL-27 production was promoted by type-I IFN, suggesting that β-herpesviridae exploit the immune-regulatory properties of this antiviral pathway to establish chronicity. Further, our data reveal that cytokine signaling events during initial infection profoundly influence virus chronicity

    PEG−peptide conjugates

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    The remarkable diversity of the self-assembly behavior of PEG−peptides is reviewed, including self-assemblies formed by PEG−peptides with β-sheet and α-helical (coiled-coil) peptide sequences. The modes of self-assembly in solution and in the solid state are discussed. Additionally, applications in bionanotechnology and synthetic materials science are summarized

    Estimating magnetic filling factors from Zeeman–Doppler magnetograms

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    V.S., S.P.M., and A.J.F.acknowledge funding from the European Research Council (ERC) under the European Unions Horizon 2020 research and innovation programme (grant agreement No. 682393 AWESoMeStars). S.B.S. acknowledges funding via the Austrian Space Application Programme (ASAP) of the Austrian Research Promotion Agency (FFG) within ASAP11, the FWF NFN project S11601-N16 and the sub-project S11604-N16. A. A.V. acknowledges funding received from the Irish Research Council Laureate Awards 2017/2018.Low-mass stars are known to have magnetic fields that are believed to be of dynamo origin. Two complementary techniques are principally used to characterize them. Zeeman–Doppler imaging (ZDI) can determine the geometry of the large-scale magnetic field while Zeeman broadening can assess the total unsigned flux including that associated with small-scale structures such as spots. In this work, we study a sample of stars that have been previously mapped with ZDI. We show that the average unsigned magnetic flux follows an activity-rotation relation separating into saturated and unsaturated regimes. We also compare the average photospheric magnetic flux recovered by ZDI, BV, with that recovered by Zeeman broadening studies, BI. In line with previous studies, BV ranges from a few % to ~20% of BI. We show that a power-law relationship between BV and BI exists and that ZDI recovers a larger fraction of the magnetic flux in more active stars. Using this relation, we improve on previous attempts to estimate filling factors, i.e., the fraction of the stellar surface covered with magnetic field, for stars mapped only with ZDI. Our estimated filling factors follow the well-known activity-rotation relation, which is in agreement with filling factors obtained directly from Zeeman broadening studies. We discuss the possible implications of these results for flux tube expansion above the stellar surface and stellar wind models.Publisher PDFPeer reviewe
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