Effects of bronchodilators on dynamic hyperinflation following hyperventilation in patients with COPD

‘The definitive version is available at www.blackwell-synergy.com '.ArticleRespirology. 12(1): 93-99 (2007)journal articl

Molecular Clouds associated with the Type Ia SNR N103B in the Large Magellanic Cloud

N103B is a Type Ia supernova remnant (SNR) in the Large Magellanic Cloud (LMC). We carried out new $^{12}$CO($J$ = 3-2) and $^{12}$CO($J$ = 1-0) observations using ASTE and ALMA. We have confirmed the existence of a giant molecular cloud (GMC) at $V_\mathrm{LSR}$ $\sim$245 km s$^{-1}$ towards the southeast of the SNR using ASTE $^{12}$CO($J$ = 3-2) data at an angular resolution of $\sim$25$"$ ($\sim$6 pc in the LMC). Using the ALMA $^{12}$CO($J$ = 1-0) data, we have spatially resolved CO clouds along the southeastern edge of the SNR with an angular resolution of $\sim$1.8$"$ ($\sim$0.4 pc in the LMC). The molecular clouds show an expanding gas motion in the position-velocity diagram with an expansion velocity of $\sim5$ km s$^{-1}$. The spatial extent of the expanding shell is roughly similar to that of the SNR. We also find tiny molecular clumps in the directions of optical nebula knots. We present a possible scenario that N103B exploded in the wind-bubble formed by the accretion winds from the progenitor system, and is now interacting with the dense gas wall. This is consistent with a single-degenerate scenario.Comment: 12 pages, 1 table, 8 figures, accepted for publication in The Astrophysical Journal (ApJ

Neutral pion emission from accelerated protons in the supernova remnant W44

We present the AGILE gamma-ray observations in the energy range 50 MeV - 10 GeV of the supernova remnant (SNR) W44, one of the most interesting systems for studying cosmic-ray production. W44 is an intermediate-age SNR (20, 000 years) and its ejecta expand in a dense medium as shown by a prominent radio shell, nearby molecular clouds, and bright [SII] emitting regions. We extend our gamma-ray analysis to energies substantially lower than previous measurements which could not conclusively establish the nature of the radiation. We find that gamma-ray emission matches remarkably well both the position and shape of the inner SNR shocked plasma. Furthermore, the gamma-ray spectrum shows a prominent peak near 1 GeV with a clear decrement at energies below a few hundreds of MeV as expected from neutral pion decay. Here we demonstrate that: (1) hadron-dominated models are consistent with all W44 multiwavelength constraints derived from radio, optical, X-ray, and gamma-ray observations; (2) ad hoc lepton-dominated models fail to explain simultaneously the well-constrained gamma-ray and radio spectra, and require a circumstellar density much larger than the value derived from observations; (3) the hadron energy spectrum is well described by a power-law (with index s = 3.0 \pm 0.1) and a low-energy cut-off at Ec = 6 \pm 1 GeV. Direct evidence for pion emission is then established in an SNR for the first time.Comment: accepted for publication on ApJ

Associated molecular and atomic clouds with X-ray shell of superbubble 30 Doradus C in the LMC

30 Doradus C is a superbubble which emits the brightest nonthermal X- and TeV gamma-rays in the Local Group. In order to explore detailed connection between the high energy radiation and the interstellar medium, we have carried out new CO and HI observations using the Atacama Large Millimeter$/$Submillimeter Array (ALMA), Atacama Submillimeter Telescope Experiment, and the Australia Telescope Compact Array with resolutions of up to 3 pc. The ALMA data of $^{12}$CO($J$ = 1-0) emission revealed 23 molecular clouds with the typical diameters of $\sim$6-12 pc and masses of $\sim$600-10000 $M_{\odot}$. The comparison with the X-rays of $XMM$-$Newton$ at $\sim$3 pc resolution shows that X-rays are enhanced toward these clouds. The CO data were combined with the HI to estimate the total interstellar protons. Comparison of the interstellar proton column density and the X-rays revealed that the X-rays are enhanced with the total proton. These are most likely due to the shock-cloud interaction modeled by the magnetohydrodynamical simulations (Inoue et al. 2012, ApJ, 744, 71). Further, we note a trend that the X-ray photon index varies with distance from the center of the high-mass star cluster, suggesting that the cosmic-ray electrons are accelerated by one or multiple supernovae in the cluster. Based on these results we discuss the role of the interstellar medium in cosmic-ray particle acceleration.Comment: 20 pages, 14 figures, 3 tables, accepted for publication in The Astrophysical Journa

ALMA Observations of Supernova Remnant N49 in the LMC. I. Discovery of CO Clumps Associated with X-Ray and Radio Continuum Shells

N49 (LHA 120-N49) is a bright X-ray supernova remnant (SNR) in the Large Magellanic Cloud. We present new 12CO (J = 1–0, 3–2), H i, and 1.4 GHz radio continuum observations of the SNR N49 using Mopra, ASTE, ALMA, and ATCA. We have newly identified three H i clouds using ATCA with an angular resolution of ~20'': one associated with the SNR and the others located in front of the SNR. Both the CO and H i clouds in the velocity range from 281 to 291 km s−1 are spatially correlated with both the soft X-rays (0.2–1.2 keV) and the hard X-rays (2.0–7.0 keV) of N49 on a ~10 pc scale. CO 3–2/1–0 intensity ratios indicate higher values of the CO cloud toward the SNR shell with an angular resolution of ~45'', and thus a strong interaction was suggested. Using the ALMA, we have spatially resolved CO clumps embedded within or along the southeastern rim of N49 with an angular resolution of ~3''. Three of the CO clumps are rim brightened on a 0.7–2 pc scale in both hard X-rays and the radio continuum: this provides further evidence for dynamical interactions between the CO clumps and the SNR shock wave. The enhancement of the radio synchrotron radiation can be understood in terms of magnetic field amplification around the CO clumps via a shock–cloud interaction. We also present a possible scenario in which the recombining plasma that dominates the hard X-rays from N49 was formed via thermal conduction between the SNR shock waves and the cold/dense molecular clumps

GABAA Receptor-Mediated Acceleration of Aging-Associated Memory Decline in APP/PS1 Mice and Its Pharmacological Treatment by Picrotoxin

Advanced age and mutations in the genes encoding amyloid precursor protein (APP) and presenilin (PS1) are two serious risk factors for Alzheimer's disease (AD). Finding common pathogenic changes originating from these risks may lead to a new therapeutic strategy. We observed a decline in memory performance and reduction in hippocampal long-term potentiation (LTP) in both mature adult (9–15 months) transgenic APP/PS1 mice and old (19–25 months) non-transgenic (nonTg) mice. By contrast, in the presence of bicuculline, a GABAA receptor antagonist, LTP in adult APP/PS1 mice and old nonTg mice was larger than that in adult nonTg mice. The increased LTP levels in bicuculline-treated slices suggested that GABAA receptor-mediated inhibition in adult APP/PS1 and old nonTg mice was upregulated. Assuming that enhanced inhibition of LTP mediates memory decline in APP/PS1 mice, we rescued memory deficits in adult APP/PS1 mice by treating them with another GABAA receptor antagonist, picrotoxin (PTX), at a non-epileptic dose for 10 days. Among the saline vehicle-treated groups, substantially higher levels of synaptic proteins such as GABAA receptor α1 subunit, PSD95, and NR2B were observed in APP/PS1 mice than in nonTg control mice. This difference was insignificant among PTX-treated groups, suggesting that memory decline in APP/PS1 mice may result from changes in synaptic protein levels through homeostatic mechanisms. Several independent studies reported previously in aged rodents both an increased level of GABAA receptor α1 subunit and improvement of cognitive functions by long term GABAA receptor antagonist treatment. Therefore, reduced LTP linked to enhanced GABAA receptor-mediated inhibition may be triggered by aging and may be accelerated by familial AD-linked gene products like Aβ and mutant PS1, leading to cognitive decline that is pharmacologically treatable at least at this stage of disease progression in mice

Gene Expression Changes in GABAA Receptors and Cognition Following Chronic Ketamine Administration in Mice

Ketamine is a well-known anesthetic agent and a drug of abuse. Despite its widespread use and abuse, little is known about its long-term effects on the central nervous system. The present study was designed to evaluate the effect of long-term (1- and 3-month) ketamine administration on learning and memory and associated gene expression levels in the brain. The Morris water maze was used to assess spatial memory and gene expression changes were assayed using Affymetrix Genechips; a focus on the expression of GABAA receptors that mediate a tonic inhibition in the brain, was confirmed by quantitative real-time PCR and western blot. Compared with saline controls, there was a decline in learning and memory performance in the ketamine-treated mice. Genechip results showed that 110 genes were up-regulated and 136 genes were down-regulated. An ontology analysis revealed the most significant effects of ketamine were on GABAA receptors. In particular, there was a significant up-regulation of both mRNA and protein levels of the alpha 5 subunit (Gabra5) of the GABAA receptors in the prefrontal cortex. In conclusion, chronic exposure to ketamine impairs working memory in mice, which may be explained at least partly by up-regulation of Gabra5 subunits in the prefrontal cortex

Fluorescence Quantum Yield of Thioflavin T in Rigid Isotropic Solution and Incorporated into the Amyloid Fibrils

In this work, the fluorescence of thioflavin T (ThT) was studied in a wide range of viscosity and temperature. It was shown that ThT fluorescence quantum yield varies from 0.0001 in water at room temperature to 0.28 in rigid isotropic solution (T/η→0). The deviation of the fluorescence quantum yield from unity in rigid isotropic solution suggests that fluorescence quantum yield depends not only on the ultra-fast oscillation of ThT fragments relative to each other in an excited state as was suggested earlier, but also depends on the molecular configuration in the ground state. This means that the fluorescence quantum yield of the dye incorporated into amyloid fibrils must depend on its conformation, which, in turn, depends on the ThT environment. Therefore, the fluorescence quantum yield of ThT incorporated into amyloid fibrils can differ from that in the rigid isotropic solution. In particular, the fluorescence quantum yield of ThT incorporated into insulin fibrils was determined to be 0.43. Consequently, the ThT fluorescence quantum yield could be used to characterize the peculiarities of the fibrillar structure, which opens some new possibilities in the ThT use for structural characterization of the amyloid fibrils