Previous studies of immune response to Haemophilus influenzae after exacerbations of chronic obstructive pulmonary disease (COPD) have yielded contradictory results. Using homologous (infecting) ...strains and immunoassays to surface-exposed epitopes, we tested the hypothesis that adults with COPD make new antibodies to strain-specific, surface-exposed epitopes on H. influenzae after exacerbations. We collected clinical information, sputum, and serum monthly and during exacerbations from 81 patients with COPD over 56 months. Serum antibodies to H. influenzae after exacerbations associated with H. influenzae in sputum were detected with whole bacterial cell ELISA and bactericidal assays. An immune response to homologous H. influenzae occurred after 22 of 36 (61.1%) exacerbations with newly acquired strains compared with 7 of 33 (21.2%) exacerbations with preexisting strains (odds ratio OR = 4.4; 95%, 1.8 to 10.8; p = 0.001). An absence of an immune response was strongly associated with complement sensitivity (OR = 0.03; 95% confidence interval, 0.003 to 0.22; p = 0.001). New bactericidal antibodies developed after exacerbations were highly strain specific, showing bactericidal activity for only 11 of 90 (12.2%) heterologous strains. Development of an immune response to H. influenzae supports its role in causing exacerbations. The strain specificity of the immune response likely represents a mechanism of recurrent exacerbations.
This is the fourth data paper publishing lightcurve survey work of 52 Near Earth Asteroids (NEAs) using 10 telescopes available to the EURONEAR network between 2017 and 2020. Forty six targets were ...not observed before our runs (88% of the sample) but some of these were targeted during the same oppositions mainly by Brian Warner. We propose new periods for 20 targets (38% of the sample), confirming published data for 20 targets, while our results for 8 targets do not match published data. We secured periods for 15 targets (29% of the sample), candidate periods for 23 objects (44%), tentative periods for 11 asteroids (21%), and have derived basic information about 3 targets (6% of the sample). We calculated the lower limit of the ellipsoid shape ratios
a
/
b
for 46 NEAs (including 13 PHAs). We confirmed or suggested 4 binary objects, recommending two of them for follow-up during future dedicated campaigns.
Context.
Microlensing provides a unique opportunity to detect non-luminous objects. In the rare cases that the Einstein radius
θ
E
and microlensing parallax
π
E
can be measured, it is possible to ...determine the mass of the lens. With technological advances in both ground- and space-based observatories, astrometric and interferometric measurements are becoming viable, which can lead to the more routine determination of
θ
E
and, if the microlensing parallax is also measured, the mass of the lens.
Aims.
We present the photometric analysis of Gaia19bld, a high-magnification (
A
≈ 60) microlensing event located in the southern Galactic plane, which exhibited finite source and microlensing parallax effects. Due to a prompt detection by the
Gaia
satellite and the very high brightness of
I
= 9.05 mag at the peak, it was possible to collect a complete and unique set of multi-channel follow-up observations, which allowed us to determine all parameters vital for the characterisation of the lens and the source in the microlensing event.
Methods.
Gaia19bld was discovered by the
Gaia
satellite and was subsequently intensively followed up with a network of ground-based observatories and the
Spitzer
Space Telescope. We collected multiple high-resolution spectra with Very Large Telescope (VLT)/X-shooter to characterise the source star. The event was also observed with VLT Interferometer (VLTI)/PIONIER during the peak. Here we focus on the photometric observations and model the light curve composed of data from
Gaia
,
Spitzer
, and multiple optical, ground-based observatories. We find the best-fitting solution with parallax and finite source effects. We derived the limit on the luminosity of the lens based on the blended light model and spectroscopic distance.
Results.
We compute the mass of the lens to be 1.13 ± 0.03
M
⊙
and derive its distance to be 5.52
−0.64
+0.35
kpc. The lens is likely a main sequence star, however its true nature has yet to be verified by future high-resolution observations. Our results are consistent with interferometric measurements of the angular Einstein radius, emphasising that interferometry can be a new channel for determining the masses of objects that would otherwise remain undetectable, including stellar-mass black holes.
We report the discovery and analysis of a planet in the microlensing event OGLE-2018-BLG-0799. The planetary signal was observed by several ground-based telescopes, and the planet-host mass ratio is ...q = (2.65 ± 0.16) × 10(−3). The ground-based observations yield a constraint on the angular Einstein radius θE, and the microlensing parallax vector πE, is strongly constrained by the Spitzer data. However, the 2019 Spitzer baseline data reveal systematics in the Spitzer photometry, so there is ambiguity in the magnitude of the parallax. In our preferred interpretation, a full Bayesian analysis using a Galactic model indicates that the planetary system is composed of an Mplanet = 0.26+0.22 −0.11M(J) planet orbiting an Mhost = 0.093+0.082 −0.038 Mʘ , at a distance of DL = 3.71+3.24 −1.70 kpc. An alternate interpretation of the data shifts the localization of the minima along the arc-shaped microlens parallax constraints. This, in turn, yields a more massive host with median mass of 0.13 Mʘ at a distance of 6.3 kpc. This analysis demonstrates the robustness of the osculating circles formalism, but shows that further investigation is needed to assess how systematics affect the specific localization of the microlens parallax vector and, consequently, the inferred physical parameters.
2′,7′-Dichlorodihydrofluorescein (DCFH2) is one of the most widely used probes for detecting intracellular oxidative stress, but requires a catalyst to be oxidized by hydrogen peroxide or superoxide ...and reacts nonspecifically with oxidizing radicals. Thiyl radicals are produced when many radicals are “repaired” by thiols, but are oxidizing agents and thus potentially capable of oxidizing DCFH2. The aim of this study was to investigate the reactivity of thiol-derived radicals toward DCFH2 and its oxidized, fluorescent form 2′,7′-dichlorofluorescein (DCF). Thiyl radicals derived from oxidation of glutathione (GSH) or cysteine (CysSH) oxidized DCFH2 with rate constants at pH 7.4 of ∼4 or ∼2×107 M−1 s−1, respectively. Both the rates of oxidation and the yields of DCF were pH-dependent. Glutathione-derived radicals interacted with DCF, resulting in the formation of DCFH absorbing at 390 nm and loss of fluorescence; in contrast, cysteine-derived radicals did not cause any depletion of DCF fluorescence. We postulate that the observed apparent difference in reactivity between GS and CysS toward DCF is related to the formation of carbon-centered, reducing radicals from base-catalyzed isomerization of GS. DCF formation from interaction of DCFH2 with GS was inhibited by oxygen in a concentration-dependent manner over the physiological range. These data indicate that in applying DCFH2 to measure oxidizing radicals in biological systems, we have to consider not only the initial competition between thiols and DCFH2 for the oxidizing radicals, but also subsequent reactions of thiol-derived radicals, together with variables—including pH and oxygen concentration—which control thiyl radical chemistry.
PD-L1, as assessed by immunohistochemistry, is a predictive biomarker for immuno-oncology treatment in lung cancer. Different scoring methods have been used to assess its status, resulting in a wide ...range of positivity rates. We use the European Thoracic Oncology Platform Lungscape non-small cell lung carcinoma cohort to explore this issue. PD-L1 expression was assessed via immunohistochemistry on tissue microarrays (up to four cores per case), using the DAKO 28-8 immunohistochemistry assay, following a two-round external quality assessment procedure. All samples were analyzed under the same protocol. Cross-validation of scoring between tissue microarray and whole sections was performed in 10% randomly selected samples. Cutoff points considered: ≥1, 50 (primarily), and 25%. At the two external quality assessment rounds, tissue microarray scoring agreement rates between pathologists were: 73% and 81%. There were 2008 cases with valid immunohistochemistry tissue microarray results (50% all cores evaluable). Concordant cases at 1, 25, and 50% were: 85, 91, and 93%. Tissue microarray core results were identical for 70% of cases. Sensitivity of the tissue microarray method for 1, 25, and 50% was: 80, 78, and 79% (specificity: 90, 95, 98%). Complete agreement between tissue microarrays and whole sections was achieved for 60% of the cases. Highest sensitivity rates for 1% and 50% cutoffs were detected for higher number of cores. Underestimation of PD-L1 expression on small samples is more common than overestimation. We demonstrated that classification of PD-L1 on small biopsy samples does not represent the overall expression of PD-L1 in all non-small cell cancer carcinoma cases, although the majority of cases are 'correctly' classified. In future studies, sampling more and larger biopsies, recording the biopsy size and tumor load may permit further refinement, increasing predictive accuracy.
Inflammation is an essential component of the normal mammalian host tissue response and plays an important role during cardiovascular and musculoskeletal diseases. Given the important role of ...inflammation on the host tissue response after injury, understanding this process represents essential aspects of biomedical research, tissue engineering, and regenerative medicine. Macrophages are central players during the inflammatory response with an extensive role during wound healing. These cells exhibit a spectrum of activation states that span from pro-inflammatory to pro-healing phenotypes. The phenotype of the macrophages can have profound influences on the progression of disease or injury. As such, understanding and subsequent modulation of macrophage phenotype represents an exciting target area for regenerative medicine therapies. In this chapter, we describe the role of macrophages in specific cases of injury and disease. After myocardial infarction, a biphasic response of pro- and anti-inflammatory macrophages are involved in the remodeling process. In volumetric muscle loss, there is an intricate communication between inflammatory cells and progenitor cells affecting repair processes. Osteoarthritis is characterized by increased levels of pro-inflammatory macrophages over an extended period of time with significant impact on the progression of the disease. By harnessing the complex role of macrophages, enhanced therapeutic treatments can be developed that enhance the normal healing response as well as help the survival of therapeutic cells delivered to the site of injury.
Context.
Brown dwarfs are transition objects between stars and planets that are still poorly understood, for which several competing mechanisms have been proposed to describe their formation. Mass ...measurements are generally difficult to carry out for isolated objects as well as for brown dwarfs orbiting low-mass stars, which are often too faint for a spectroscopic follow-up.
Aims.
Microlensing provides an alternative tool for the discovery and investigation of such faint systems. Here, we present an analysis of the microlensing event OGLE-2019-BLG-0033/MOA-2019-BLG-035, which is caused by a binary system composed of a brown dwarf orbiting a red dwarf.
Methods.
Thanks to extensive ground observations and the availability of space observations from
Spitzer,
it has been possible to obtain accurate estimates of all microlensing parameters, including the parallax, source radius, and orbital motion of the binary lens.
Results.
Following an accurate modeling process, we found that the lens is composed of a red dwarf with a mass of
M
1
= 0.149 ± 0.010
M
⊙
and a brown dwarf with a mass of
M
2
= 0.0463 ± 0.0031
M
⊙
at a projected separation of
a
⊥
= 0.585 au. The system has a peculiar velocity that is typical of old metal-poor populations in the thick disk. A percent-level precision in the mass measurement of brown dwarfs has been achieved only in a few microlensing events up to now, but will likely become more common in the future thanks to the
Roman
space telescope.
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