Regular exercise reduces the risk of cancer and disease recurrence. Yet the mechanisms behind this protection remain to be elucidated. In this study, tumor-bearing mice randomized to voluntary wheel ...running showed over 60% reduction in tumor incidence and growth across five different tumor models. Microarray analysis revealed training-induced upregulation of pathways associated with immune function. NK cell infiltration was significantly increased in tumors from running mice, whereas depletion of NK cells enhanced tumor growth and blunted the beneficial effects of exercise. Mechanistic analyses showed that NK cells were mobilized by epinephrine, and blockade of β-adrenergic signaling blunted training-dependent tumor inhibition. Moreover, epinephrine induced a selective mobilization of IL-6-sensitive NK cells, and IL-6-blocking antibodies blunted training-induced tumor suppression, intratumoral NK cell infiltration, and NK cell activation. Together, these results link exercise, epinephrine, and IL-6 to NK cell mobilization and redistribution, and ultimately to control of tumor growth.
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•Exercise reduces tumor incidence and growth in several mouse models•Exercise increases NK cell infiltration, thereby controlling tumor growth•Epinephrine mobilizes NK cells and β-blockade blunts the tumor suppression•Exercise-induced muscle-derived IL-6 is involved in NK cell redistribution
The beneficial effects of exercise are countless. Pedersen et al. now link exercise, cancer, and immunity and reveal that exercise decreases tumor incidence and growth by over 60% across several mouse tumor models through a direct regulation of NK cell mobilization and trafficking in an epinephrine- and IL-6-dependent manner.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Aims
We observed a microvascular structure in the cerebral cortex that has not, to our knowledge, been previously described. We have termed the structure a ‘raspberry’, referring to its appearance ...under a bright‐field microscope. We hypothesized that raspberries form through angiogenesis due to some form of brain ischaemia or hypoperfusion. The aims of this study were to quantify raspberry frequency within the cerebral cortex according to diagnosis (vascular dementia, Alzheimer's disease, frontotemporal lobar degeneration and nondemented controls) and brain regions (frontal, temporal, parietal and occipital cortices, regardless of diagnosis).
Materials and methods
In each of 10 age‐matched subjects per group, a 20‐mm section of the cerebral cortex was examined in haematoxylin‐and‐eosin‐stained sections of the frontal, temporal and parietal, and/or occipital lobes. Tests were performed to validate the haematoxylin‐and‐eosin‐based identification of relative differences between the groups, and to investigate inter‐rater variability.
Results
Raspberry frequency was highest in subjects with vascular dementia, followed by those with frontotemporal lobar degeneration, Alzheimer's disease and last, nondemented controls. The frequency of raspberries in subjects with vascular dementia differed from that of all other groups at a statistically significant level. In the cerebral lobes, there was a statistically significant difference between the frontal and occipital cortices.
Conclusions
We believe the results support the hypothesis that raspberries are a sign of angiogenesis in the adult brain. It is pertinent to discuss possible proangiogenic stimuli, including brain ischaemia (such as mild hypoperfusion due to a combination of small vessel disease and transient hypotension), neuroinflammation and protein pathology.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Context.
W Aql is an asymptotic giant branch (AGB) star with an atmospheric elemental abundance ratio C/O ≈ 0.98. It has previously been reported to have circumstellar molecular abundances ...intermediate between those of M-type and C-type AGB stars, which respectively have C/O < 1 and C/O > 1. This intermediate status is considered typical for S-type stars, although our understanding of the chemical content of their circumstellar envelopes is currently rather limited.
Aims.
We aim to assess the reported intermediate status of W Aql by analysing the line emission of molecules that have never before been observed towards this star.
Methods.
We performed observations in the frequency range 159−268 GHz with the SEPIA/B5 and PI230 instruments on the APEX telescope. We made abundance estimates through direct comparison to available spectra towards a number of well-studied AGB stars and based on rotational diagram analysis in the case of one molecule.
Results.
From a compilation of our abundance estimates and those found in the literature for two M-type (R Dor, IK Tau), two S-type (
χ
Cyg, W Aql), and two C-type stars (V Aql, IRC +10 216), we conclude that the circumstellar environment of W Aql appears considerably closer to that of a C-type AGB star than to that of an M-type AGB star. In particular, we detect emission from C
2
H, SiC
2
, SiN, and HC
3
N, molecules previously only detected towards the circumstellar environment of C-type stars. This conclusion, based on the chemistry of the gaseous component of the circumstellar environment, is further supported by reports in the literature on the presence of atmospheric molecular bands and spectral features of dust species which are typical for C-type AGB stars. Although our observations mainly trace species in the outer regions of the circumstellar environment, our conclusion matches closely that based on recent chemical equilibrium models for the inner wind of S-type stars: the atmospheric and circumstellar chemistry of S-type stars likely resembles that of C-type AGB stars much more closely than that of M-type AGB stars.
Conclusions.
Further observational investigation of the gaseous circumstellar chemistry of S-type stars is required to characterise its dependence on the atmospheric C/O. Non-equilibrium chemical models of the circumstellar environment of AGB stars need to address the particular class of S-type stars and the chemical variety that is induced by the range in atmospheric C/O.
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The asymptotic-giant-branch star R Sculptoris is surrounded by a detached shell of dust and gas. The shell originates from a thermal pulse during which the star underwent a brief period of increased ...mass loss. It has hitherto been impossible to constrain observationally the timescales and mass-loss properties during and after a thermal pulse--parameters that determine the lifetime of the asymptotic giant branch and the amount of elements returned by the star. Here we report observations of CO emission from the circumstellar envelope and shell around R Sculptoris with an angular resolution of 1.3″. What was previously thought to be only a thin, spherical shell with a clumpy structure is revealed to also contain a spiral structure. Spiral structures associated with circumstellar envelopes have been previously seen, leading to the conclusion that the systems must be binaries. Combining the observational data with hydrodynamic simulations, we conclude that R Sculptoris is a binary system that underwent a thermal pulse about 1,800 years ago, lasting approximately 200 years. About 3 × 10(-3) solar masses of material were ejected at a velocity of 14.3 km s(-1) and at a rate around 30 times higher than the pre-pulse mass-loss rate. This shows that about three times more mass was returned to the interstellar medium during and immediately after the pulse than previously thought.
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DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Context. We describe the new Swedish-ESO PI Instrument for APEX (SEPIA) receiver, which was designed and built by the Group for Advanced Receiver Development (GARD), at Onsala Space Observatory (OSO) ...in collaboration with ESO. It was installed and commissioned at the APEX telescope during 2015 with an ALMA Band 5 receiver channel and updated with a new frequency channel (ALMA Band 9) in February 2016. Aim. This manuscript aims to provide, for observers who use the SEPIA receiver, a reference in terms of the hardware description, optics and performance as well as the commissioning results. Methods. Out of three available receiver cartridge positions in SEPIA, the two current frequency channels, corresponding to ALMA Band 5, the RF band 158–211 GHz, and Band 9, the RF band 600–722 GHz, provide state-of-the-art dual polarization receivers. The Band 5 frequency channel uses 2SB SIS mixers with an average SSB noise temperature around 45 K with IF (intermediate frequency) band 4–8 GHz for each sideband providing total 4 × 4 GHz IF band. The Band 9 frequency channel uses DSB SIS mixers with a noise temperature of 75–125 K with IF band 4–12 GHz for each polarization. Results. Both current SEPIA receiver channels are available to all APEX observers.
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Aims. The sulphur compounds SO and SO2 have not been widely studied in the circumstellar envelopes of asymptotic giant branch (AGB) stars. By presenting and modelling a large number of SO and SO2 ...lines in the low mass-loss rate M-type AGB star R Dor, and modelling the available lines of those molecules in a further four M-type AGB stars, we aim to determine their circumstellar abundances and distributions. Methods. We use a detailed radiative transfer analysis based on the accelerated lambda iteration method to model circumstellar SO and SO2 line emission. We use molecular data files for both SO and SO2 that are more extensive than those previously available. Results. Using 17 SO lines and 98 SO2 lines to constrain our models for R Dor, we find an SO abundance of (6.7 ± 0.9) × 10-6 and an SO2 abundance of 5 × 10-6 with both species having high abundances close to the star. We also modelled 34SO and found an abundance of (3.1 ± 0.8) × 10-7, giving an 32SO/34SO ratio of 21.6 ± 8.5. We derive similar results for the circumstellar SO and SO2 abundances and their distributions for the low mass-loss rate object W Hya. For the higher mass-loss rate stars, we find shell-like SO distributions with peak abundances that decrease and peak abundance radii that increase with increasing mass-loss rate. The positions of the peak SO abundance agree very well with the photodissociation radii of H2O. We also modelled SO2 in two higher mass-loss rate stars but our models for these were less conclusive. Conclusions. We conclude that for the low mass-loss rate stars, the circumstellar SO and SO2 abundances are much higher than predicted by chemical models of the extended stellar atmosphere. These two species may also account for all the available sulphur. For the higher mass-loss rate stars we find evidence that SO is most efficiently formed in the circumstellar envelope, most likely through the photodissociation of H2O and the subsequent reaction between S and OH. The S-bearing parent molecule does not appear to be H2S. The SO2 models for the higher mass-loss rate stars are less conclusive, but suggest an origin close to the star for this species. This is not consistent with current chemical models. The combined circumstellar SO and SO2 abundances are significantly lower than that of sulphur for these higher mass-loss rate objects.
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Context. The outflows of oxygen-rich asymptotic giant branch (AGB) stars are thought to be driven by radiation pressure due to the scattering of photons on relatively large grains, with sizes of ...tenths of microns. The details of the formation of dust in the extended atmospheres of these stars and, therefore, the mass-loss process, is still not well understood. Aims. We aim to constrain the distribution of the gas and the composition and properties of the dust grains that form in the inner circumstellar environment of the archetypal Mira variable o Cet. Methods. We obtained quasi-simultaneous observations using ALMA and SPHERE/ZIMPOL on the Very Large Telescope (VLT) to probe the distribution of gas and large dust grains, respectively. Results. The polarized light images show dust grains around Mira A, but also around the companion, Mira B, and a dust trail that connects the two sources. The ALMA observations show that dust around Mira A is contained in a high-gas-density region with a significant fraction of the grains that produce the polarized light located at the edge of this region. Hydrodynamical and wind-driving models show that dust grains form efficiently behind shock fronts caused by stellar pulsation or convective motions. The distance at which we observe the density decline (a few tens of au) is, however, significantly larger than expected for stellar-pulsation-induced shocks. Other possibilities for creating the high-gas-density region are a recent change in the mass-loss rate of Mira A or interactions with Mira B. We are not able to determine which of these scenarios is correct. We constrained the gas density, temperature, and velocity within a few stellar radii from the star by modelling the CO v = 1, J = 3−2 line. We find a mass (~3.8 ± 1.3) × 10−4 M⊙ to be contained between the stellar millimetre photosphere, R⋆338 GHz $R^{\textrm{338~GHz}}_{\star}$ R⋆338 GHz , and 4 R⋆338 GHz $4~R^{\textrm{338~GHz}}_{\star}$ 4 R⋆338 GHz . Our best-fit models with lower masses also reproduce the 13CO v = 0, J = 3−2 line emission from this region well. We find TiO2 and AlO abundances corresponding to 4.5% and <0.1% of the total titanium and aluminium expected for a gas with solar composition. The low abundance of AlO allows for a scenario in which Al depletion into dust happens already very close to the star, as expected from thermal dust emission observations and theoretical calculations of Mira variables. The relatively large abundance of aluminium for a gas with solar composition allows us to constrain the presence of aluminium oxide grains based on the scattered light observations and on the gas densities we obtain. These models imply that aluminium oxide grains could account for a significant fraction of the total aluminium atoms in this region only if the grains have sizes ≲0.02 μm. This is an order of magnitude smaller than the maximum sizes predicted by dust-formation and wind-driving models. Conclusions. The study we present highlights the importance of coordinated observations using different instruments to advance our understanding of dust nucleation, dust growth, and wind driving in AGB stars.
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Context.
The
N
K
a
K
c
= 4
04
−3
13
transitions of ortho-CH
2
between 68 and 71 GHz were first detected toward the Orion-KL and W51 Main star-forming regions. Given their high upper level energies ...(225 K) above the ground state, they were naturally thought to arise in dense, hot molecular cores near newly formed stars. However, this has not been confirmed by further observations of these lines and their origin has remained unclear. Generally, there is a scarcity of observational data for CH
2
and, while it is an important compound in the astrochemical context, its actual occurrence in astronomical sources is poorly constrained.
Aims.
In this work, we aim to investigate the nature of the elusive CH
2
emission, address its association with hot cores, and examine alternative possibilities for its origin. Owing to its importance in carbon chemistry, we also extend the search for CH
2
lines by observing an assortment of regions, guided by the hypothesis that the observed CH
2
emission is likely to arise from the hot gas environment of photodissociation regions (PDRs).
Methods.
We carried out our observations first using the Kitt Peak 12 m telescope to verify the original detection of CH
2
toward different positions in the central region of the Orion Molecular Cloud 1. These were followed-up by deep integrations using the higher angular resolution of the Onsala 20 m telescope. We also searched for the
N
K
a
K
c
= 2
12
−3
03
transitions of para-CH
2
between 440–445 GHz toward the Orion giant molecular cloud complex using the APEX 12 m telescope. We also obtained auxiliary data for carbon recombination lines with the Effelsberg 100 m telescope and employing archival far infrared data.
Results.
The present study, along with other recent observations of the Orion region reported here, rule out the possibility of an association with gas that is both hot and dense. We find that the distribution of the CH
2
emission closely follows that of the CII 158
μ
m emission, while CH
2
is undetected toward the hot core itself. The observations suggest, rather, that its extended emission arises from hot but dilute layers of PDRs and not from the denser parts of such regions as in the case of the Orion Bar. This hypothesis was corroborated by comparisons of the observed CH
2
line profiles with those of carbon radio recombination lines (CRRLs), which are well-known PDR tracers. In addition, we report the detection of the 70 GHz fine- and hyperfine structure components of ortho-CH
2
toward the W51 E, W51 M, W51 N, W49 N, W43, W75 N, DR21, and S140 star-forming regions, and three of the
N
K
a
K
c
= 4
04
−3
13
fine- and hyperfine structure transitions between 68–71 GHz toward W3 IRS5. While we have no information on the spatial distribution of CH
2
in these regions, aside from that in W51, we again see a correspondence between the profiles of CH
2
lines and those of CRRLs. We see a stronger CH
2
emission toward the extended HII region W51 M rather than toward the much more massive and denser W51 E and N regions, which strongly supports the origin of CH
2
in extended dilute gas. We also report the non-detection of the 2
12
−3
03
transitions of para-CH
2
toward Orion. Furthermore, using a non-LTE radiative transfer analysis, we can constrain the gas temperatures and H
2
density to (163 ± 26) K and (3.4 ± 0.3) × 10
3
cm
−3
, respectively, for the 68–71 GHz ortho-CH
2
transitions toward W3 IRS5, for which we have a data set of the highest quality. This analysis confirms our hypothesis that CH
2
originates inwarm and dilute PDR layers. Our analysis suggests that for the excitation conditions under the physical conditions that prevail in such an environment, these lines are masering, with weak level inversion. The resulting amplification of the lines’ spontaneousemission greatly aids in their detection.
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The Spectral and Photometric Imaging REceiver (SPIRE), is the Herschel Space Observatory`s submillimetre camera and spectrometer. It contains a three-band imaging photometer operating at 250, 350 and ...500 μm, and an imaging Fourier-transform spectrometer (FTS) which covers simultaneously its whole operating range of 194–671 μm (447–1550 GHz). The SPIRE detectors are arrays of feedhorn-coupled bolometers cooled to 0.3 K. The photometer has a field of view of 4´× 8´, observed simultaneously in the three spectral bands. Its main operating mode is scan-mapping, whereby the field of view is scanned across the sky to achieve full spatial sampling and to cover large areas if desired. The spectrometer has an approximately circular field of view with a diameter of 2.6´. The spectral resolution can be adjusted between 1.2 and 25 GHz by changing the stroke length of the FTS scan mirror. Its main operating mode involves a fixed telescope pointing with multiple scans of the FTS mirror to acquire spectral data. For extended source measurements, multiple position offsets are implemented by means of an internal beam steering mirror to achieve the desired spatial sampling and by rastering of the telescope pointing to map areas larger than the field of view. The SPIRE instrument consists of a cold focal plane unit located inside the Herschel cryostat and warm electronics units, located on the spacecraft Service Module, for instrument control and data handling. Science data are transmitted to Earth with no on-board data compression, and processed by automatic pipelines to produce calibrated science products. The in-flight performance of the instrument matches or exceeds predictions based on pre-launch testing and modelling: the photometer sensitivity is comparable to or slightly better than estimated pre-launch, and the spectrometer sensitivity is also better by a factor of 1.5–2.
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Context.
Isotopologue line intensity ratios of circumstellar molecules have been widely used to trace the photospheric elemental isotopic ratios of evolved stars. However, depending on the molecular ...species and the physical conditions of the environment, the isotopologue ratio in the circumstellar envelope (CSE) may deviate considerably from the stellar atmospheric value.
Aims.
In this paper, we aim to examine how the
12
CO/
13
CO and H
12
CN/H
13
CN abundance ratios vary radially due to chemical reactions in the outflows of asymptotic giant branch (AGB) stars and the effect of excitation and optical depth on the resulting line intensity ratios. We study both carbon-rich (C-type) and oxygen-rich (O-type) CSEs.
Methods.
We performed chemical modeling to derive radial abundance distributions of our selected species in the CSEs over a wide range of mass-loss rates (10
−8
<
Ṁ
< 10
−4
M
⊙
yr
−1
). We used these as input in a non-local thermodynamic equilibrium radiative transfer code to derive the line intensities of several ground-state rotational transitions. We also test the influence of stellar parameters, physical conditions in the outflows, the intensity of the interstellar radiation field, and the importance of considering the chemical networks in our model results.
Results.
We quantified deviations from the atmospheric value for typical outflows. We find that the circumstellar value of
12
CO/
13
CO can deviate from its atmospheric value by up to 25–94% and 6–60% for C- and O-type CSEs, respectively, in radial ranges that depend on the mass-loss rate. We show that variations of the intensity of the interstellar radiation field and the gas kinetic temperature can significantly influence the CO isotopologue abundance ratio in the outer CSEs of both C-type and O-type. On the contrary, the H
12
CN/H
13
CN abundance ratio is stable throughout the CSEs for all tested mass-loss rates. The radiative transfer modeling shows that the integrated line intensity ratio
I
12
CO
/
I
13
CO
of different rotational transitions varies significantly for stars with mass-loss rates in the range from 10
−7
to 10
−6
M
⊙
yr
−1
due to combined chemical and excitation effects. In contrast, the excitation conditions for the HCN isotopologues are the same for both isotopologues.
Conclusions.
We demonstrate the importance of using the isotopologue abundance profiles from detailed chemical models as inputs to radiative transfer models in the interpretation of isotopologue observations. Previous studies of circumstellar CO isotopologue ratios are based on multi-transition data for individual sources and it is difficult to estimate the errors in the reported values due to assumptions that are not entirely correct according to this study. If anything, previous studies may have overestimated the circumstellar
12
CO/
13
CO abundance ratio. The use of the HCN molecule as a tracer of C isotope ratios is affected by fewer complicating problems, but we note that the corrections for high optical depths are very large in the case of high-mass-loss-rate C-type CSEs; and in O-type CSEs the H
13
CN lines may be too weak to detect.
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