An increase in respiratory rate and expiratory flow limitation can facilitate dynamic hyperinflation (DH), which may cause an element of the intrathoracic pressure in connection with the worsening of ...venous return, with negative effect on stroke volume (SV) and cardiac output (CO). It has been unclassified, whether poor circulatory adaptation to exercise can be attributed to DH or poor cardio-vascular performance itself in COPD. Only a subset of COPD patients exhibit dynamic hyperinflation during exercise.
We designed a study to show how lung mechanical and cardiovascular parameters change in hyperinflated and non-hyperinflated COPD patients during exercise with a new experimental set-up. Thirty-three COPD patients with similar severity of COPD and left ventricular performance (20 men, 13 women, mean±SD age: 65,36±6,95 years) participated. We measured the cardiovascular parameters with a non-invasive device (Finometer-pro) including the left ventricular ejection time index (LVETi) and estimated the change of DH with inspiratory capacity (IC) manoeuvres during exercise.
Twenty-one subjects exhibited DH (DH group) and 12 did not (non-DH group). The measurement results were given in mean ± SD and difference between the values measured during maximal load and rest also (ΔX = Xmax.load-Xrest). ΔSV and ΔCO were significantly higher in non-DH vs. DH patients (ΔSV: non-DH 9,7 ± 13,22 ml vs. DH -3,6 ± 14,34 ml, p = 0.0142; ΔCO: non-DH 2,26 ± 1,46 l/min vs. DH 0,88 ± 1,35 l/min, p = 0.0024). LVETi was not different between the two groups. Calculated oxygen delivery (DO2) during maximal load was significantly higher in non-DH group.
We concluded that worse cardiovascular adaptation to exercise of COPD patients can be associated with exercise-induced DH in a similar cardiovascular aged COPD group.
PB1-F2 is a 90 amino acid protein that is expressed from the +1 open reading frame in the PB1 gene of some influenza A viruses and has been shown to contribute to viral pathogenicity. Notably, a ...serine at position 66 (66S) in PB1-F2 is known to increase virulence compared to an isogenic virus with an asparagine (66N) at this position. Recently, we found that an influenza virus expressing PB1-F2 N66S suppresses interferon (IFN)-stimulated genes in mice. To characterize this phenomenon, we employed several in vitro assays. Overexpression of the A/Puerto Rico/8/1934 (PR8) PB1-F2 protein in 293T cells decreased RIG-I mediated activation of an IFN-β reporter and secretion of IFN as determined by bioassay. Of note, the PB1-F2 N66S protein showed enhanced IFN antagonism activity compared to PB1-F2 wildtype. Similar observations were found in the context of viral infection with a PR8 PB1-F2 N66S virus. To understand the relationship between NS1, a previously described influenza virus protein involved in suppression of IFN synthesis, and PB1-F2, we investigated the induction of IFN when NS1 and PB1-F2 were co-expressed in an in vitro transfection system. In this assay we found that PB1-F2 N66S further reduced IFN induction in the presence of NS1. By inducing the IFN-β reporter at different levels in the signaling cascade, we found that PB1-F2 inhibited IFN production at the level of the mitochondrial antiviral signaling protein (MAVS). Furthermore, immunofluorescence studies revealed that PB1-F2 co-localizes with MAVS. In summary, we have characterized the anti-interferon function of PB1-F2 and we suggest that this activity contributes to the enhanced pathogenicity seen with PB1-F2 N66S- expressing influenza viruses.
ZK60 Magnesium tubing has been friction extruded from as-cast billets and T5 conditioned bars using Shear Assisted Processing and Extrusion (ShAPE). Tubes having an outer diameter of 50.8 mm and wall ...thickness of 1.9 mm were extruded with >20 times less ram force compared to conventional extrusion due to the unique shearing conditions and tooling inherent to ShAPE. Microstructures of the as-cast billet and T5 bar feedstock materials were significantly different from each other in terms of grain size, texture, and second phase distribution; yet the resulting microstructures after ShAPE were remarkably similar. An average grain size of 4–5 μm, 20° tilt of basal texture away from the extrusion axis, and refined second phases having a uniform distribution were achieved independent of the feedstock material. Hardness for as-extruded and artificially aged tubes are presented with isotropic behavior explained by detailed microstructural analysis. This work suggests that bulk ZK60 magnesium alloys extrusions may be fabricated in a single step, with microstructures that are unobtainable with conventional extrusion.
Patients with chronic obstructive pulmonary disease (COPD) show systemic consequences, such as chronic systemic inflammation leading to changes in the airway, airway penetrability, and endothelial ...function. Endothelial dysfunction is characterized by a list of alterations of endothelium towards reduced vasodilation, proinflammatory state, detachment and apoptosis of endothelial cells, and development of atherosclerosis. COPD-induced endothelial dysfunction is associated with elevated cardiovascular risk. The increment of physical activities such as pulmonary rehabilitation (PR) training have a significant effect on COPD, thus, PR can be an integrative part of COPD treatment. In this narrative review the focus is on the function of endothelial inflammatory mediators cytokines, chemokines, and cellular proteases and pulmonary endothelial cells and endothelial dysfunction in COPD as well as the effects of dysfunction of the endothelium may play in COPD-related pulmonary hypertension. The relationship between smoking and endothelial dysfunction is also discussed. The connection between different pulmonary rehabilitation programs, arterial stiffness and pulse wave velocity (PWV) is presented. Endothelial dysfunction is a significant prognostic factor of COPD, which can be characterized by PWV. We discuss future considerations, like training programs, as an important part of the treatment that has a favorable impact on the endothelial function.
Highly pathogenic avian influenza A viruses (HPAIV) of the H5N1 subtype occasionally transmit from birds to humans and can cause severe systemic infections in both hosts. PB1-F2 is an alternative ...translation product of the viral PB1 segment that was initially characterized as a pro-apoptotic mitochondrial viral pathogenicity factor. A full-length PB1-F2 has been present in all human influenza pandemic virus isolates of the 20(th) century, but appears to be lost evolutionarily over time as the new virus establishes itself and circulates in the human host. In contrast, the open reading frame (ORF) for PB1-F2 is exceptionally well-conserved in avian influenza virus isolates. Here we perform a comparative study to show for the first time that PB1-F2 is a pathogenicity determinant for HPAIV (A/Viet Nam/1203/2004, VN1203 (H5N1)) in both mammals and birds. In a mammalian host, the rare N66S polymorphism in PB1-F2 that was previously described to be associated with high lethality of the 1918 influenza A virus showed increased replication and virulence of a recombinant VN1203 H5N1 virus, while deletion of the entire PB1-F2 ORF had negligible effects. Interestingly, the N66S substituted virus efficiently invades the CNS and replicates in the brain of Mx+/+ mice. In ducks deletion of PB1-F2 clearly resulted in delayed onset of clinical symptoms and systemic spreading of virus, while variations at position 66 played only a minor role in pathogenesis. These data implicate PB1-F2 as an important pathogenicity factor in ducks independent of sequence variations at position 66. Our data could explain why PB1-F2 is conserved in avian influenza virus isolates and only impacts pathogenicity in mammals when containing certain amino acid motifs such as the rare N66S polymorphism.
The cosmological utility of galaxy cluster catalogues is primarily limited by our ability to calibrate the relation between halo mass and observable mass proxies such as cluster richness, X-ray ...luminosity or the Sunyaev-Zeldovich signal. Projection effects are a particularly pernicious systematic effect that can impact observable mass proxies; structure along the line of sight can both bias and increase the scatter of the observable mass proxies used in cluster abundance studies. In this work, we develop an empirical method to characterize the impact of projection effects on redMaPPer cluster catalogues. We use numerical simulations to validate our method and illustrate its robustness. We demonstrate that modeling of projection effects is a necessary component for cluster abundance studies capable of reaching $\approx 5\%$ mass calibration uncertainties (e.g. the Dark Energy Survey Year 1 sample). Specifically, ignoring the impact of projection effects in the observable--mass relation --- i.e. marginalizing over a log-normal model only --- biases the posterior of the cluster normalization condition $S_8 \equiv \sigma_8 (\Omega_{\rm m}/0.3)^{1/2}$ by $\Delta S_8 =0.05$, more than twice the uncertainty in the posterior for such an analysis.
We investigate potential gains in cosmological constraints from the combination of galaxy clustering and galaxy-galaxy lensing by optimizing the lens galaxy sample selection using information from ...Dark Energy Survey (DES) Year 3 data and assuming the DES Year 1 metacalibration sample for the sources. We explore easily reproducible selections based on magnitude cuts in i-band as a function of (photometric) redshift, zphot, and benchmark the potential gains against those using the well-established redMaGiC E. Rozo et al., Mon. Not. R. Astron. Soc. 461, 1431 (2016) sample. We focus on the balance between density and photometric redshift accuracy, while marginalizing over a realistic set of cosmological and systematic parameters. Our optimal selection, the MagLim sample, satisfies i < 4zphot + 18 and has ∼ 30% wider redshift distributions but ∼ 3.5 times more galaxies than redMaGiC. Assuming a w CDM model (i.e. with a free parameter for the dark energy equation of state) and equivalent scale cuts to mitigate nonlinear effects, this leads to 40% increase in the figure of merit for the pair combinations of Ωm, w, and σ8, and gains of 16% in σ8, 10% in Ωm, and 12% in w. Similarly, in Λ CDM, we find an improvement of 19% and 27% on σ8 and Ωm, respectively. We also explore flux-limited samples with a flat magnitude cut finding that the optimal selection, i < 22.2, has ∼ 7 times more galaxies and ∼ 20% wider redshift distributions compared to MagLim, but slightly worse constraints. We show that our results are robust with respect to the assumed galaxy bias and photometric redshift uncertainties with only moderate further gains from increased number of tomographic bins or the inclusion of bin cross-correlations, except in the case of the flux-limited sample, for which these gains are more significant.
The Kéromnès et al. (2013) mechanism for hydrogen combustion has been optimized using a large set of indirect experimental data, consisting of ignition measurements in shock tubes (566 datapoints in ...43 datasets) and rapid compression machines (219/19), and flame velocity measurements (364/59), covering wide ranges of temperature (800K–2300K), pressure (0.1bar–65bar) and equivalence ratio (φ=0.2–5.0). According to the sensitivity analysis carried out at each experimental datapoint, 30 Arrhenius parameters and 3 third body collision efficiency parameters of 11 elementary reactions could be optimized using these experimental data. 1749 directly measured rate coefficient values in 56 datasets belonging to the 11 reaction steps were also utilized. Prior uncertainty ranges of the rate coefficients were determined from literature data. Mechanism optimization has led to a new hydrogen combustion mechanism, a set of newly recommended rate parameters with their covariance matrix, and temperature-dependent posterior uncertainty ranges of the rate coefficients. The optimized mechanism generated here was tested together with 13 recent hydrogen combustion mechanisms and proved to be the best one.
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