5,098 research outputs found

    The Radiated Energy Budget of Chromospheric Plasma in a Major Solar Flare Deduced From Multi-Wavelength Observations

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    This paper presents measurements of the energy radiated by the lower solar atmosphere, at optical, UV, and EUV wavelengths, during an X-class solar flare (SOL2011-02-15T01:56) in response to an injection of energy assumed to be in the form of nonthermal electrons. Hard X-ray observations from RHESSI were used to track the evolution of the parameters of the nonthermal electron distribution to reveal the total power contained in flare accelerated electrons. By integrating over the duration of the impulsive phase, the total energy contained in the nonthermal electrons was found to be >2×1031>2\times10^{31} erg. The response of the lower solar atmosphere was measured in the free-bound EUV continua of H I (Lyman), He I, and He II, plus the emission lines of He II at 304\AA\ and H I (Lyα\alpha) at 1216\AA\ by SDO/EVE, the UV continua at 1600\AA\ and 1700\AA\ by SDO/AIA, and the WL continuum at 4504\AA, 5550\AA, and 6684\AA, along with the Ca II H line at 3968\AA\ using Hinode/SOT. The summed energy detected by these instruments amounted to 3×1030\sim3\times10^{30} erg; about 15% of the total nonthermal energy. The Lyα\alpha line was found to dominate the measured radiative losses. Parameters of both the driving electron distribution and the resulting chromospheric response are presented in detail to encourage the numerical modelling of flare heating for this event, to determine the depth of the solar atmosphere at which these line and continuum processes originate, and the mechanism(s) responsible for their generation.Comment: 14 pages, 18 figures. Accepted for publication in Astrophysics Journa

    NKX2-5 regulates vessel remodelling in scleroderma-associated pulmonary arterial hypertension.

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    NKX2-5 is a member of the homeobox-containing transcription factors critical in regulating tissue differentiation in development. Here, we report a role for NKX2-5 in vascular smooth muscle cell phenotypic modulation in vitro and in vascular remodelling in vivo. NKX2-5 is up-regulated in scleroderma (SSc) patients with pulmonary arterial hypertension. Suppression of NKX2-5 expression in smooth muscle cells, halted vascular smooth muscle proliferation and migration, enhanced contractility and blocked the expression of the extracellular matrix genes. Conversely, overexpression of NKX2-5 suppressed the expression of contractile genes (ACTA2, TAGLN, CNN1) and enhanced the expression of matrix genes (COL1) in vascular smooth muscle cells. In vivo, conditional deletion of NKX2-5 attenuated blood vessel remodelling and halted the progression to hypertension in the mouse chronic hypoxia mouse model. This study revealed that signals related to injury such as serum and low confluence, which induce NKX2-5 expression in cultured cells, is potentiated by TGFβ and further enhanced by hypoxia. The effect of TGFβ was sensitive to ERK5 and PI3K inhibition. Our data suggest a pivotal role for NKX2-5 in the phenotypic modulation of smooth muscle cells during pathological vascular remodelling and provide proof of concept for therapeutic targeting of NKX2-5 in vasculopathies

    Electron-Spin Excitation Coupling in an Electron Doped Copper Oxide Superconductor

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    High-temperature (high-Tc) superconductivity in the copper oxides arises from electron or hole doping of their antiferromagnetic (AF) insulating parent compounds. The evolution of the AF phase with doping and its spatial coexistence with superconductivity are governed by the nature of charge and spin correlations and provide clues to the mechanism of high-Tc superconductivity. Here we use a combined neutron scattering and scanning tunneling spectroscopy (STS) to study the Tc evolution of electron-doped superconducting Pr0.88LaCe0.12CuO4-delta obtained through the oxygen annealing process. We find that spin excitations detected by neutron scattering have two distinct modes that evolve with Tc in a remarkably similar fashion to the electron tunneling modes in STS. These results demonstrate that antiferromagnetism and superconductivity compete locally and coexist spatially on nanometer length scales, and the dominant electron-boson coupling at low energies originates from the electron-spin excitations.Comment: 30 pages, 12 figures, supplementary information include

    Palmar-divergent dislocation of the scaphoid and the lunate

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    We describe a patient with palmar-divergent dislocation of the scaphoid and lunate. After successful closed reduction, the scapholunate and lunotriquetral ligaments were sutured through the dorsal approach, and the anterior capsule was sutured through the palmar approach. The scapholunate and lunotriquetral joints were fixed with Kirschner wires for 7 weeks. At the 1-year follow-up, magnetic resonance imaging showed no evidence of avascular necrosis of the scaphoid or lunate, and radiographs showed no evidence of the dorsal and volar intercalated segment instability patterns associated with carpal instability. However, flexion of the scaphoid and a break in Gilula’s line remained. To our knowledge, this is the first report showing treatment of palmar-divergent dislocation of the scaphoid and lunate by suturing the carpal interosseous ligaments

    Imaging cytoplasmic cAMP in mouse brainstem neurons

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    <p>Abstract</p> <p>Background</p> <p>cAMP is an ubiquitous second messenger mediating various neuronal functions, often as a consequence of increased intracellular Ca<sup>2+ </sup>levels. While imaging of calcium is commonly used in neuroscience applications, probing for cAMP levels has not yet been performed in living vertebrate neuronal tissue before.</p> <p>Results</p> <p>Using a strictly neuron-restricted promoter we virally transduced neurons in the organotypic brainstem slices which contained pre-Bötzinger complex, constituting the rhythm-generating part of the respiratory network. Fluorescent cAMP sensor Epac1-camps was expressed both in neuronal cell bodies and neurites, allowing us to measure intracellular distribution of cAMP, its absolute levels and time-dependent changes in response to physiological stimuli. We recorded [cAMP]<sub>i </sub>changes in the micromolar range after modulation of adenylate cyclase, inhibition of phosphodiesterase and activation of G-protein-coupled metabotropic receptors. [cAMP]<sub>i </sub>levels increased after membrane depolarisation and release of Ca<sup>2+ </sup>from internal stores. The effects developed slowly and reached their maximum after transient [Ca<sup>2+</sup>]<sub>i </sub>elevations subsided. Ca<sup>2+</sup>-dependent [cAMP]<sub>i </sub>transients were suppressed after blockade of adenylate cyclase with 0.1 mM adenylate cyclase inhibitor 2'5'-dideoxyadenosine and potentiated after inhibiting phosphodiesterase with isobutylmethylxanthine and rolipram. During paired stimulations, the second depolarisation and Ca<sup>2+ </sup>release evoked bigger cAMP responses. These effects were abolished after inhibition of protein kinase A with H-89 pointing to the important role of phosphorylation of calcium channels in the potentiation of [cAMP]<sub>i </sub>transients.</p> <p>Conclusion</p> <p>We constructed and characterized a neuron-specific cAMP probe based on Epac1-camps. Using viral gene transfer we showed its efficient expression in organotypic brainstem preparations. Strong fluorescence, resistance to photobleaching and possibility of direct estimation of [cAMP] levels using dual wavelength measurements make the probe useful in studies of neurons and the mechanisms of their plasticity. Epac1-camps was applied to examine the crosstalk between Ca<sup>2+ </sup>and cAMP signalling and revealed a synergism of actions of these two second messengers.</p

    Association of Long-Acting Injectable Antipsychotics and Oral Antipsychotics With Disease Relapse, Health Care Use, and Adverse Events Among People With Schizophrenia

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    IMPORTANCE: Evidence for improved clinical outcomes with long-acting injectable antipsychotics (LAIAs) vs oral antipsychotics (OAs) is limited in Asian populations and special patient groups, including older people (>65 years), people with substance use, and early initiators of LAIAs. OBJECTIVE: To compare the risk of disease relapse, health care use, and adverse events associated with the use of LAIAs vs OAs among people in Hong Kong with schizophrenia. DESIGN, SETTINGS, AND PARTICIPANTS: In this self-controlled case series study, individuals with a diagnosis of schizophrenia who were prescribed LAIAs and OAs between January 1, 2004, and December 31, 2019, were identified from the Clinical Database Analysis and Reporting System of the Hong Kong Hospital Authority. Data analysis was conducted from May to August in 2021. EXPOSURES: Use of LAIAs vs OAs. MAIN OUTCOMES AND MEASURES: Risk of disease relapse (hospitalizations for psychiatric disorders, hospitalizations for schizophrenia, and suicide attempts), health care use (all-cause emergency department visits and hospitalizations), and adverse events (hospitalizations for somatic disorders, hospitalizations for cardiovascular diseases, and extrapyramidal symptoms) between the period in which patients were treated with LAIAs and the period in which patients were treated with OAs were compared using Poisson regression. RESULTS: Of the 70 396 individuals with schizophrenia (37 200 women [52.8%]; mean [SD] age, 44.2 [15.8] years), 23 719 (33.7%) were prescribed both LAIAs and OAs. Compared with OAs, LAIAs were associated with a lower risk of hospitalizations for any cause (n = 20 973; incidence rate ratio [IRR], 0.63 [95% CI, 0.61-0.65]), hospitalizations for psychiatric disorders (n = 19 283; IRR, 0.52 [95% CI, 0.50-0.53]), hospitalizations for schizophrenia (n = 18 385; IRR, 0.53 [95% CI, 0.51-0.55]), and incident suicide attempts (n = 1453; IRR, 0.56 [95% CI, 0.44-0.71]). During full treatment with LAIAs, there was a reduction in hospitalizations for somatic disorders (n = 15 396; IRR, 0.88 [95% CI, 0.85-0.91]), hospitalizations for cardiovascular diseases (n = 3710; IRR, 0.88 [95% CI, 0.81-0.96]), and extrapyramidal symptoms (n = 22 182; IRR, 0.86 [95% CI, 0.82-0.91]) compared with full treatment with OAs. No significant difference was found for emergency department visits. Similar associations were observed during the subsequent treatment periods (beyond 90 days) and among older people and those with substance use, except for an increased risk of extrapyramidal symptoms among older people when initiating LAIAs (first 90 days). Compared with late initiators, early LAIA initiators had a greater reduction in these outcome events. CONCLUSIONS AND RELEVANCE: This self-controlled case series study of people in Hong Kong with schizophrenia suggests that LAIAs were associated with a lower risk of disease relapse and hospitalization than OAs, without an increased risk of adverse events. Clinicians should more broadly consider the long-term use of LAIAs for Chinese people with schizophrenia, especially early in the course of illness

    In situ epitaxial MgB2 thin films for superconducting electronics

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    A thin film technology compatible with multilayer device fabrication is critical for exploring the potential of the 39-K superconductor magnesium diboride for superconducting electronics. Using a Hybrid Physical-Chemical Vapor Deposition (HPCVD) process, it is shown that the high Mg vapor pressure necessary to keep the MgB2_2 phase thermodynamically stable can be achieved for the {\it in situ} growth of MgB2_2 thin films. The films grow epitaxially on (0001) sapphire and (0001) 4H-SiC substrates and show a bulk-like TcT_c of 39 K, a JcJ_c(4.2K) of 1.2×1071.2 \times 10^7 A/cm2^2 in zero field, and a Hc2(0)H_{c2}(0) of 29.2 T in parallel magnetic field. The surface is smooth with a root-mean-square roughness of 2.5 nm for MgB2_2 films on SiC. This deposition method opens tremendous opportunities for superconducting electronics using MgB2_2

    Mosaic DNA imports with interspersions of recipient sequence after natural transformation of Helicobacter pylori

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    Helicobacter pylori colonizes the gastric mucosa of half of the human population, causing gastritis, ulcers, and cancer. H. pylori is naturally competent for transformation by exogenous DNA, and recombination during mixed infections of one stomach with multiple H. pylori strains generates extensive allelic diversity. We developed an in vitro transformation protocol to study genomic imports after natural transformation of H. pylori. The mean length of imported fragments was dependent on the combination of donor and recipient strain and varied between 1294 bp and 3853 bp. In about 10% of recombinant clones, the imported fragments of donor DNA were interrupted by short interspersed sequences of the recipient (ISR) with a mean length of 82 bp. 18 candidate genes were inactivated in order to identify genes involved in the control of import length and generation of ISR. Inactivation of the antimutator glycosylase MutY increased the length of imports, but did not have a significant effect on ISR frequency. Overexpression of mutY strongly increased the frequency of ISR, indicating that MutY, while not indispensable for ISR formation, is part of at least one ISR-generating pathway. The formation of ISR in H. pylori increases allelic diversity, and contributes to the uniquely low linkage disequilibrium characteristic of this pathogen

    Cross-sectional associations between sleep duration, sedentary time, physical activity, and adiposity indicators among Canadian preschool-aged children using compositional analyses

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    Abstract Background Sleep duration, sedentary behaviour, and physical activity are three co-dependent behaviours that fall on the movement/non-movement intensity continuum. Compositional data analyses provide an appropriate method for analyzing the association between co-dependent movement behaviour data and health indicators. The objectives of this study were to examine: (1) the combined associations of the composition of time spent in sleep, sedentary behaviour, light-intensity physical activity (LPA), and moderate- to vigorous-intensity physical activity (MVPA) with adiposity indicators; and (2) the association of the time spent in sleep, sedentary behaviour, LPA, or MVPA with adiposity indicators relative to the time spent in the other behaviours in a representative sample of Canadian preschool-aged children. Methods Participants were 552 children aged 3 to 4 years from cycles 2 and 3 of the Canadian Health Measures Survey. Sedentary time, LPA, and MVPA were measured with Actical accelerometers (Philips Respironics, Bend, OR USA), and sleep duration was parental reported. Adiposity indicators included waist circumference (WC) and body mass index (BMI) z-scores based on World Health Organization growth standards. Compositional data analyses were used to examine the cross-sectional associations. Results The composition of movement behaviours was significantly associated with BMI z-scores (p = 0.006) but not with WC (p = 0.718). Further, the time spent in sleep (BMI z-score: γ sleep  = −0.72; p = 0.138; WC: γ sleep  = −1.95; p = 0.285), sedentary behaviour (BMI z-score: γ SB  = 0.19; p = 0.624; WC: γ SB  = 0.87; p = 0.614), LPA (BMI z-score: γ LPA  = 0.62; p = 0.213, WC: γ LPA  = 0.23; p = 0.902), or MVPA (BMI z-score: γ MVPA  = −0.09; p = 0.733, WC: γ MVPA  = 0.08; p = 0.288) relative to the other behaviours was not significantly associated with the adiposity indicators. Conclusions This study is the first to use compositional analyses when examining associations of co-dependent sleep duration, sedentary time, and physical activity behaviours with adiposity indicators in preschool-aged children. The overall composition of movement behaviours appears important for healthy BMI z-scores in preschool-aged children. Future research is needed to determine the optimal movement behaviour composition that should be promoted in this age group

    Z' Bosons at Colliders: a Bayesian Viewpoint

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    We revisit the CDF data on di-muon production to impose constraints on a large class of Z' bosons occurring in a variety of E_6 GUT based models. We analyze the dependence of these limits on various factors contributing to the production cross-section, showing that currently systematic and theoretical uncertainties play a relatively minor role. Driven by this observation, we emphasize the use of the Bayesian statistical method, which allows us to straightforwardly (i) vary the gauge coupling strength, g', of the underlying U(1)'; (ii) include interference effects with the Z' amplitude (which are especially important for large g'); (iii) smoothly vary the U(1)' charges; (iv) combine these data with the electroweak precision constraints as well as with other observables obtained from colliders such as LEP 2 and the LHC; and (v) find preferred regions in parameter space once an excess is seen. We adopt this method as a complementary approach for a couple of sample models and find limits on the Z' mass, generally differing by only a few percent from the corresponding CDF ones when we follow their approach. Another general result is that the interference effects are quite relevant if one aims at discriminating between models. Finally, the Bayesian approach frees us of any ad hoc assumptions about the number of events needed to constitute a signal or exclusion limit for various actual and hypothetical reference energies and luminosities at the Tevatron and the LHC.Comment: PDFLaTeX, 24 pages, 7 figures. Version with improved tables and figure
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