Acute allergic symptoms are caused by allergen-induced crosslinking of allergen-specific immunoglobulin E (IgE) bound to Fc-epsilon receptors on effector cells. Desensitization with allergen-specific ...immunotherapy (SIT) has been used for over a century, but the dominant protective mechanism remains unclear. One consistent observation is increased allergen-specific IgG, thought to competitively block allergen binding to IgE. Here we show that the blocking potency of the IgG response to Cat-SIT is heterogeneous. Next, using two potent, pre-selected allergen-blocking monoclonal IgG antibodies against the immunodominant cat allergen Fel d 1, we demonstrate that increasing the IgG/IgE ratio reduces the allergic response in mice and in cat-allergic patients: a single dose of blocking IgG reduces clinical symptoms in response to nasal provocation (ANCOVA, p = 0.0003), with a magnitude observed at day 8 similar to that reported with years of conventional SIT. This study suggests that simply augmenting the blocking IgG/IgE ratio may reverse allergy.
Abstract Background When compared with warfarin, edoxaban significantly reduced cardiovascular mortality in the ENGAGE AF-TIMI 48 trial. We studied the possible reasons leading to this reduction. ...Methods ENGAGE AF-TIMI 48 was a double-blind, double-dummy comparison of warfarin with 2 regimens of once-daily edoxaban in 21,105 patients with atrial fibrillation followed for 2.8 years (median). Causes of deaths in the intention-to-treat population were classified as cardiovascular (including fatal bleeding and ischemic stroke), malignancy, or non-cardiovascular/non-malignancy by an independent, blinded, clinical endpoint committee . Deaths also were adjudicated as directly due to bleeding (i.e., fatal), or bleeding contributing to death, or neither. Results There were 839 total deaths (4.35%/yr) in the warfarin arm, compared with 773 (3.99%/yr, p=0.08) with the higher-dose edoxaban regimen, and 737 (3.80%/yr, p=0.006) with the lower-dose edoxaban regimen. No significant differences between treatments were observed in: 1) any of the 3 most common causes of cardiovascular death (sudden cardiac, heart failure, ischemic stroke), 2) fatal malignancies, 3) other non-cardiovascular death. There were 124 fatal bleeds, 65 with warfarin, significantly fewer with the higher-dose (n=35, p=0.003) and lower-dose (n=24, p<0.001) edoxaban regimens. There were 101 bleeding events with warfarin that were either fatal or that contributed to death. There were significantly fewer with the higher-dose (n=59, P=0.001) and lower-dose (n=54, P<0.001) edoxaban regimens. Conclusions Fewer total and cardiovascular deaths were observed with edoxaban as compared to warfarin in the ENGAGE AF-TIMI 48 trial, and this predominantly resulted from significantly lower rate of major bleeding with edoxaban. Edoxaban reduces mortality both directly (less fatal bleeding) and indirectly (fewer bleeding-related complications and interruptions in therapy after non-fatal bleeding).
Bnip3 (Bcl-2/adenovirus E1B 19-kDa-interacting protein 3) is a mitochondrial BH3-only protein that contributes to cell death through activation of the mitochondrial pathway of apoptosis. Bnip3 is ...also known to induce autophagy, but the functional role of autophagy is unclear. In this study, we investigated the relationship between mitochondrial dysfunction and upregulation of autophagy in response to Bnip3 in cells lacking Bax and Bak. We found that Bnip3 induced mitochondrial autophagy in the absence of mitochondrial membrane permeabilization and Bax/Bak. Also, co-immunoprecipitation experiments showed that Bnip3 interacted with the autophagy protein LC3 (microtubule-associated protein light chain 3). Although Bax-/Bak-deficient cells were resistant to Bnip3-mediated cell death, inhibition of mitochondrial autophagy induced necrotic cell death. When investigating why these mitochondria had to be removed by autophagy, we discovered that Bnip3 reduced both nuclear- and mitochondria-encoded proteins involved in oxidative phosphorylation. Interestingly, Bnip3 had no effect on other mitochondrial proteins, such as Tom20 and MnSOD, or actin and tubulin in the cytosol. Bnip3 did not seem to reduce transcription or translation of these proteins. However, we found that Bnip3 caused an increase in mitochondrial protease activity, suggesting that Bnip3 might promote degradation of proteins in the mitochondria. Thus, Bnip3-mediated impairment of mitochondrial respiration induces mitochondrial turnover by activating mitochondrial autophagy.
The
Gaia
-ESO Survey is an European Southern Observatory (ESO) public spectroscopic survey that targeted 10
5
stars in the Milky Way covering the major populations of the disk, bulge and halo. The ...observations were made using FLAMES on the VLT obtaining both UVES high (
R
~ 47 000) and GIRAFFE medium (
R
~ 20 000) resolution spectra. The analysis of the
Gaia
-ESO spectra was the work of multiple analysis teams (nodes) within five working groups (WG). The homogenisation of the stellar parameters within WG11 (high resolution observations of FGK stars) and the homogenisation of the stellar parameters within WG10 (medium resolution observations of FGK stars) is described here. In both cases, the homogenisation was carried out using a Bayesian Inference method developed specifically for the
Gaia
-ESO Survey by WG11. The method was also used for the chemical abundance homogenisation within WG11, however, the WG10 chemical abundance data set was too sparsely populated so basic corrections for each node analysis were employed for the homogenisation instead. The WG10 homogenisation primarily used the cross-match of stars with WG11 as the reference set in both the stellar parameter and chemical abundance homogenisation. In this way the WG10 homogenised results have been placed directly onto the WG11 stellar parameter and chemical abundance scales. The reference set for the metal-poor end was sparse which limited the effectiveness of the homogenisation in that regime. For WG11, the total number of stars for which stellar parameters were derived was 6 231 with typical uncertainties for
T
eff
, log
g
and Fe/H of 32 K, 0.05 and 0.05 respectively. One or more chemical abundances out of a possible 39 elements were derived for 6 188 of the stars. For WG10, the total number of stars for which stellar parameters were derived was 76 675 with typical uncertainties for
T
eff
, log
g
and Fe/H of 64 K, 0.15 and 0.07 respectively. One or more chemical abundances out of a possible 30 elements were derived for 64177 of the stars.
Context.
In the last 15 years different ground-based spectroscopic surveys have been started (and completed) with the general aim of delivering stellar parameters and elemental abundances for large ...samples of Galactic stars, complementing
Gaia
astrometry. Among those surveys, the
Gaia
-ESO Public Spectroscopic Survey, the only one performed on a 8m class telescope, was designed to target 100 000 stars using FLAMES on the ESO VLT (both Giraffe and UVES spectrographs), covering all the Milky Way populations, with a special focus on open star clusters.
Aims.
This article provides an overview of the survey implementation (observations, data quality, analysis and its success, data products, and releases), of the open cluster survey, of the science results and potential, and of the survey legacy. A companion article reviews the overall survey motivation, strategy, Giraffe pipeline data reduction, organisation, and workflow.
Methods.
We made use of the information recorded and archived in the observing blocks; during the observing runs; in a number of relevant documents; in the spectra and master catalogue of spectra; in the parameters delivered by the analysis nodes and the working groups; in the final catalogue; and in the science papers. Based on these sources, we critically analyse and discuss the output and products of the Survey, including science highlights. We also determined the average metallicities of the open clusters observed as science targets and of a sample of clusters whose spectra were retrieved from the ESO archive.
Results.
The Gaia-ESO Survey has determined homogeneous good-quality radial velocities and stellar parameters for a large fraction of its more than 110 000 unique target stars. Elemental abundances were derived for up to 31 elements for targets observed with UVES. Lithium abundances are delivered for about 1/3 of the sample. The analysis and homogenisation strategies have proven to be successful; several science topics have been addressed by the
Gaia
-ESO consortium and the community, with many highlight results achieved.
Conclusions.
The final catalogue will be released through the ESO archive in the first half of 2022, including the complete set of advanced data products. In addition to these results, the
Gaia
-ESO Survey will leave a very important legacy, for several aspects and for many years to come.
Field Line Resonances (FLRs) are a critical component in Earth's magnetospheric dynamics, associated with the transfer of energy between Ultra Low Frequency waves and local plasma populations. In ...this study we investigate how the polarisation of FLRs are impacted by cold plasma density distributions during geomagnetic storms. We present an analysis of Van Allen Probe A observations, where the spacecraft traversed a storm time plasmaspheric plume. We show that the polarisation of the FLR is significantly altered at the sharp azimuthal density gradient of the plume boundary, where the polarisation is intermediate with significant poloidal and toroidal components. These signatures are consistent with magnetohydrodynamic modeling results, providing the first observational evidence of a 3D FLR associated with a plume in Earth's magnetosphere. These results demonstrate the importance of cold plasma in controlling wave dynamics in the magnetosphere, and have important implications for wave‐particle interactions at a range of energies.
Plain Language Summary
Earth's space environment is home to electrons and ions across a wide range of energies, trapped in the region by our global geomagnetic field. Energy can be transferred to and from the trapped particles through oscillations in the magnetic field, and these processes are responsible for the extreme energization of trapped electrons to hazardous levels for local spacecraft. In this paper we explore a type of magnetic field oscillation termed Field Line Resonances (FLRs): standing waves on a field line analogous to the oscillatory motion of guitar strings. We use spacecraft observations to show that the direction of the field line oscillations changes significantly depending on the density of the background plasma. The results confirm previous modeling work, and are the first observational evidence of 3D FLRs at a plume. The findings have important consequences for how FLRs transfer energy between the electrons and ions.
Key Points
We present the first observational evidence of a 3D Field Line Resonance at the sharp density gradient of a plume edge
The observed polarisation change confirms magnetohydrodynamic modeling results and predictions made by Elsden and Wright (2022)
The presence of 3D Field Line Resonances during storm times has impacts for how Ultra Low Frequency waves couple and interact with local plasma
ABSTRACT
We present the VST ATLAS Quasar Survey, consisting of ∼1229 000 quasar (QSO) candidates with 16 < g < 22.5 over ∼4700 deg2. The catalogue is based on VST ATLAS+NEOWISE imaging surveys and ...aims to reach a QSO sky density of 130 deg−2 for $z$ < 2.2 and ∼30 deg−2 for $z$ > 2.2. To guide our selection, we use X-ray/UV/optical/MIR data in the extended William Herschel Deep Field (WHDF) where we find a g < 22.5 broad-line QSO density of 269 ± 67 deg−2, roughly consistent with the expected ∼196 deg−2. We find that ∼25 per cent of our QSOs are morphologically classed as optically extended. Overall, we find that in these deep data, MIR, UV, and X-ray selections are ∼70–90 per cent complete while X-ray suffers less contamination than MIR and UV. MIR is however more sensitive than X-ray or UV to $z$ > 2.2 QSOs at g < 22.5 and the $S_X(0.5-10\, {\rm keV})\gt 1\times 10^{-14}$ ergs cm−2 s−1 limit of eROSITA. We adjust the selection criteria from our previous 2QDES pilot survey and prioritize VST ATLAS candidates that show both UV and MIR excess, also selecting candidates initially classified as extended. We test our selections using data from DESI (which will be released in DR1) and 2dF to estimate the efficiency and completeness, and we use ANNz2 to determine photometric redshifts. Applying over the ∼4700 deg2 ATLAS area gives us $\sim 917\,000\, z\lt 2.2$ QSO candidates of which 472 000 are likely to be $z$ < 2.2 QSOs, implying a sky density of ∼100 deg−2, which our WHDF analysis suggests will rise to at least 130 deg−2 when eROSITA X-ray candidates are included. At $z$ > 2.2, we find ∼310() 000 candidates, of which 169 000 are likely to be QSOs for a sky density of ∼36 deg−2.
The INT Galactic Plane Survey (IGAPS) is the merger of the optical photometric surveys, IPHAS and UVEX, based on data from the
Isaac Newton
Telescope (INT) obtained between 2003 and 2018. Here, we ...present the IGAPS point source catalogue. It contains 295.4 million rows providing photometry in the filters,
i
,
r
, narrow-band H
α
,
g
, and
U
RGO
. The IGAPS footprint fills the Galactic coordinate range, |
b
| < 5° and 30° <
ℓ
< 215°. A uniform calibration, referred to as the Pan-STARRS system, is applied to
g
,
r
, and
i
, while the H
α
calibration is linked to
r
and then is reconciled via field overlaps. The astrometry in all five bands has been recalculated in the reference frame of
Gaia
Data Release 2. Down to
i
∼ 20 mag (Vega system), most stars are also detected in
g
,
r
, and H
α
. As exposures in the
r
band were obtained in both the IPHAS and UVEX surveys, typically a few years apart, the catalogue includes two distinct
r
measures,
r
I
and
r
U
. The
r
10
σ
limiting magnitude is approximately 21, with median seeing of 1.1 arcsec. Between approximately 13th and 19th mag in all bands, the photometry is internally reproducible to within 0.02 mag. Stars brighter than
r
= 19.5 mag are tested for narrow-band H
α
excess signalling line emission, and for variation exceeding |
r
I
−
r
U
| = 0.2 mag. We find and flag 8292 candidate emission line stars and over 53 000 variables (both at > 5
σ
confidence).
Local neuromuscular deficits have been reported in people with patellofemoral pain. We synthesised the neuromuscular characteristics associated with patellofemoral pain to help identify ...interventional targets and potential mechanisms.
Five databases were searched for local neuromuscular characteristics in case-control studies. Electromyography, flexibility, muscle performance and cross-sectional area data were derived from functional or isolated task investigations and synthesised accordingly. An evidence gap map was constructed.
Sixty-seven studies were included. In functional tasks, electromyographic investigations showed moderate evidence of small effect for vastus medialis onset-delays relative to vastus lateralis (0.44 0.03, 0.85) during stepping/stair negotiation tasks, and higher biceps femoris mean excitation amplitudes (0.55 0.06, 1.04) in single-leg triple-hop test. In isolated tasks, we found moderate evidence of medium effect for lower Hoffman-reflex amplitude of vastus medialis (−1.12 −1.56, −0.67). Muscle performance investigations showed; strong evidence with medium and small effects for lower extensors concentric (−0.61 −0.81, −0.40) and eccentric (−0.56 −0.79, −0.33) strength, and moderate evidence of medium effect of lower isometric (−0.64 −0.87, −0.41) strength, moderate evidence with small effect for rate of force development to 30% (−0.55−0.89, −0.21), 60% (−0.57−0.90, −0.25) and medium effect to 90% (−0.76−1.43, −0.10) of maximum voluntary contraction, and small effect for lower flexors concentric strength (−0.46 −0.74, −0.19) and extensors total work (−0.48 −0.90, −0.07). Flexibility investigations showed tighter hamstrings (−0.57 −0.99, −0.14).
Differences within quadriceps and hamstrings motor-control, hamstrings tightness, and quadriceps and hamstrings weakness are associated with patellofemoral pain, and can be used to guide investigations of treatment effects.
•Ten local neuromuscular deficits have been shown to be associated with patellofemoral pain.•The specific methodologies required to detect these deficits have been identified.•Quadriceps muscle deficits have been robustly established.•Gaps in other local muscle deficits have been presented to inform future research.
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