We present Atacama Large Millimeter Array 850 m continuum observations of the Orion Nebula Cluster that provide the highest angular resolution (∼0 1 40 au) and deepest sensitivity (∼0.1 mJy) of the ...region to date. We mosaicked a field containing ∼225 optical or near-IR-identified young stars, ∼60 of which are also optically identified "proplyds." We detect continuum emission at 850 m toward ∼80% of the proplyd sample, and ∼50% of the larger sample of previously identified cluster members. Detected objects have fluxes of ∼0.5-80 mJy. We remove submillimeter flux due to free-free emission in some objects, leaving a sample of sources detected in dust emission. Under standard assumptions of isothermal, optically thin disks, submillimeter fluxes correspond to dust masses of ∼0.5-80 Earth masses. We measure the distribution of disk sizes, and find that disks in this region are particularly compact. Such compact disks are likely to be significantly optically thick. The distributions of submillimeter flux and inferred disk size indicate smaller, lower-flux disks than in lower-density star-forming regions of similar age. Measured disk flux is correlated weakly with stellar mass, contrary to studies in other star-forming regions that found steeper correlations. We find a correlation between disk flux and distance from the massive star θ1 Ori C, suggesting that disk properties in this region are influenced strongly by the rich cluster environment.
As Arctic regions warm and frozen soils thaw, the large organic carbon pool stored in permafrost becomes increasingly vulnerable to decomposition or transport. The transfer of newly mobilized carbon ...to the atmosphere and its potential influence upon climate change will largely depend on the degradability of carbon delivered to aquatic ecosystems. Dissolved organic carbon (DOC) is a key regulator of aquatic metabolism, yet knowledge of the mechanistic controls on DOC biodegradability is currently poor due to a scarcity of long-term data sets, limited spatial coverage of available data, and methodological diversity. Here, we performed parallel biodegradable DOC (BDOC) experiments at six Arctic sites (16 experiments) using a standardized incubation protocol to examine the effect of methodological differences commonly used in the literature. We also synthesized results from 14 aquatic and soil leachate BDOC studies from across the circum-arctic permafrost region to examine pan-arctic trends in BDOC. An increasing extent of permafrost across the landscape resulted in higher DOC losses in both soil and aquatic systems. We hypothesize that the unique composition of (yedoma) permafrost-derived DOC combined with limited prior microbial processing due to low soil temperature and relatively short flow path lengths and transport times, contributed to a higher overall terrestrial and freshwater DOC loss. Additionally, we found that the fraction of BDOC decreased moving down the fluvial network in continuous permafrost regions, i.e. from streams to large rivers, suggesting that highly biodegradable DOC is lost in headwater streams. We also observed a seasonal (January-December) decrease in BDOC in large streams and rivers, but saw no apparent change in smaller streams or soil leachates. We attribute this seasonal change to a combination of factors including shifts in carbon source, changing DOC residence time related to increasing thaw-depth, increasing water temperatures later in the summer, as well as decreasing hydrologic connectivity between soils and surface water as the thaw season progresses. Our results suggest that future climate warming-induced shifts of continuous permafrost into discontinuous permafrost regions could affect the degradation potential of thaw-released DOC, the amount of BDOC, as well as its variability throughout the Arctic summer. We lastly recommend a standardized BDOC protocol to facilitate the comparison of future work and improve our knowledge of processing and transport of DOC in a changing Arctic.
This paper evaluates the current status of global modeling of the organic aerosol (OA) in the troposphere and analyzes the differences between models as well as between models and observations. ...Thirty-one global chemistry transport models (CTMs) and general circulation models (GCMs) have participated in this intercomparison, in the framework of AeroCom phase II. The simulation of OA varies greatly between models in terms of the magnitude of primary emissions, secondary OA (SOA) formation, the number of OA species used (2 to 62), the complexity of OA parameterizations (gas-particle partitioning, chemical aging, multiphase chemistry, aerosol microphysics), and the OA physical, chemical and optical properties. The diversity of the global OA simulation results has increased since earlier AeroCom experiments, mainly due to the increasing complexity of the SOA parameterization in models, and the implementation of new, highly uncertain, OA sources. Diversity of over one order of magnitude exists in the modeled vertical distribution of OA concentrations that deserves a dedicated future study. Furthermore, although the OA / OC ratio depends on OA sources and atmospheric processing, and is important for model evaluation against OA and OC observations, it is resolved only by a few global models. The median global primary OA (POA) source strength is 56 Tg a−1 (range 34–144 Tg a−1) and the median SOA source strength (natural and anthropogenic) is 19 Tg a−1 (range 13–121 Tg a−1). Among the models that take into account the semi-volatile SOA nature, the median source is calculated to be 51 Tg a−1 (range 16–121 Tg a−1), much larger than the median value of the models that calculate SOA in a more simplistic way (19 Tg a−1; range 13–20 Tg a−1, with one model at 37 Tg a−1). The median atmospheric burden of OA is 1.4 Tg (24 models in the range of 0.6–2.0 Tg and 4 between 2.0 and 3.8 Tg), with a median OA lifetime of 5.4 days (range 3.8–9.6 days). In models that reported both OA and sulfate burdens, the median value of the OA/sulfate burden ratio is calculated to be 0.77; 13 models calculate a ratio lower than 1, and 9 models higher than 1. For 26 models that reported OA deposition fluxes, the median wet removal is 70 Tg a−1 (range 28–209 Tg a−1), which is on average 85% of the total OA deposition. Fine aerosol organic carbon (OC) and OA observations from continuous monitoring networks and individual field campaigns have been used for model evaluation. At urban locations, the model–observation comparison indicates missing knowledge on anthropogenic OA sources, both strength and seasonality. The combined model–measurements analysis suggests the existence of increased OA levels during summer due to biogenic SOA formation over large areas of the USA that can be of the same order of magnitude as the POA, even at urban locations, and contribute to the measured urban seasonal pattern. Global models are able to simulate the high secondary character of OA observed in the atmosphere as a result of SOA formation and POA aging, although the amount of OA present in the atmosphere remains largely underestimated, with a mean normalized bias (MNB) equal to −0.62 (−0.51) based on the comparison against OC (OA) urban data of all models at the surface, −0.15 (+0.51) when compared with remote measurements, and −0.30 for marine locations with OC data. The mean temporal correlations across all stations are low when compared with OC (OA) measurements: 0.47 (0.52) for urban stations, 0.39 (0.37) for remote stations, and 0.25 for marine stations with OC data. The combination of high (negative) MNB and higher correlation at urban stations when compared with the low MNB and lower correlation at remote sites suggests that knowledge about the processes that govern aerosol processing, transport and removal, on top of their sources, is important at the remote stations. There is no clear change in model skill with increasing model complexity with regard to OC or OA mass concentration. However, the complexity is needed in models in order to distinguish between anthropogenic and natural OA as needed for climate mitigation, and to calculate the impact of OA on climate accurately.
Alternative Lengthening of Telomeres (ALT) is a telomere maintenance pathway utilised in 15% of cancers. ALT cancers are strongly associated with inactivating mutations in ATRX; yet loss of ATRX ...alone is insufficient to trigger ALT, suggesting that additional cooperating factors are involved. We identify H3.3
and IDH1/2 mutations as two such factors in ATRX-mutated glioblastomas. Both mutations are capable of inactivating histone demethylases, and we identify KDM4B as the key demethylase inactivated in ALT. Mouse embryonic stem cells inactivated for ATRX, TP53, TERT and KDM4B (KDM4B knockout or H3.3
) show characteristic features of ALT. Conversely, KDM4B over-expression in ALT cancer cells abrogates ALT-associated features. In this work, we demonstrate that inactivation of KDM4B, through H3.3
or IDH1/2 mutations, acts in tandem with ATRX mutations to promote ALT in glioblastomas.
Evaluation of the aerosol schemes in current climate models is dependent upon the available observational data. In-situ observations from flight campaigns can provide valuable data about the vertical ...distribution of aerosol that is difficult to obtain from satellite or ground-based platforms, although they are localised in space and time. Using single-particle soot-photometer (SP2) measurements from the HIAPER Pole-to-Pole Observations (HIPPO) campaign, which consists of many vertical profiles over a large region of the Pacific, we evaluate the meridional and vertical distribution of black carbon (BC) aerosol simulated by the HadGEM3-UKCA and ECHAM5-HAM2 models. Both models show a similar pattern of overestimating the BC column burden compared to that derived from the observations, in many areas by an order of magnitude. However, by sampling the simulated BC mass mixing ratio along the flight track and comparing to the observations, we show that this discrepancy has a rather different vertical structure in the two models: in HadGEM3-UKCA the discrepancy is dominated by excess aerosol in the tropical upper troposphere, while in ECHAM5-HAM2 areas of discrepancy are spread across many different latitudes and altitudes. Using this methodology, we conduct sensitivity tests on two specific elements of the models: biomass-burning emissions and scavenging by convective precipitation. We show that, by coupling the convective scavenging more tightly with convective transport, both the column burden and vertical distribution of BC in HadGEM3-UKCA are much improved with respect to the observations, with a substantial and statistically significant increase in correlation - this demonstrates the importance of a realistic representation of this process. In contrast, updating from GFED2 to GFED3.1 biomass-burning emissions makes a more modest improvement in both models, which is not statistically significant. By comparing our results with a more traditional approach using regional- and monthly-mean vertical profile curves, we show that the point-by-point analysis allows the model improvements to be demonstrated more clearly. We also demonstrate the important role that nudged simulations (where the large-scale model dynamics are continuously relaxed towards a reanalysis) can play in this type of evaluation, allowing statistically significant differences between configurations of the aerosol scheme to be seen where the differences between the corresponding free-running simulations would not be significant.
Intrachromosomal amplification of chromosome 21 (iAMP21) defines a distinct cytogenetic subgroup of childhood B-cell precursor acute lymphoblastic leukaemia (BCP-ALL). To date, fluorescence in situ ...hybridisation (FISH), with probes specific for the RUNX1 gene, provides the only reliable detection method (five or more RUNX1 signals per cell). Patients with iAMP21 are older (median age 9 years) with a low white cell count. Previously, we demonstrated a high relapse risk when these patients were treated as standard risk. Recent studies have shown improved outcome on intensive therapy. In view of these treatment implications, accurate identification is essential. Here we have studied the cytogenetics and outcome of 530 iAMP21 patients that highlighted the association of specific secondary chromosomal and genetic changes with iAMP21 to assist in diagnosis, including the gain of chromosome X, loss or deletion of chromosome 7, ETV6 and RB1 deletions. These iAMP21 patients when treated as high risk showed the same improved outcome as those in trial-based studies regardless of the backbone chemotherapy regimen given. This study reinforces the importance of intensified treatment to reduce the risk of relapse in iAMP21 patients. This now well-defined patient subgroup should be recognised by World Health Organisation (WHO) as a distinct entity of BCP-ALL.
Skeletal muscle conveys several of the health-promoting effects of exercise; yet the underlying mechanisms are not fully elucidated. Studying skeletal muscle is challenging due to its different fiber ...types and the presence of non-muscle cells. This can be circumvented by isolation of single muscle fibers. Here, we develop a workflow enabling proteomics analysis of pools of isolated muscle fibers from freeze-dried human muscle biopsies. We identify more than 4000 proteins in slow- and fast-twitch muscle fibers. Exercise training alters expression of 237 and 172 proteins in slow- and fast-twitch muscle fibers, respectively. Interestingly, expression levels of secreted proteins and proteins involved in transcription, mitochondrial metabolism, Ca
signaling, and fat and glucose metabolism adapts to training in a fiber type-specific manner. Our data provide a resource to elucidate molecular mechanisms underlying muscle function and health, and our workflow allows fiber type-specific proteomic analyses of snap-frozen non-embedded human muscle biopsies.
ABSTRACT
In this paper, we present the X-ray analysis of Sloan Digital Sky Survey DR8 redMaPPer (SDSSRM) clusters using data products from the XMM Cluster Survey (XCS). In total, 1189 SDSSRM clusters ...fall within the XMM–Newton footprint. This has yielded 456 confirmed detections accompanied by X-ray luminosity (LX) measurements. Of these clusters, 381 have an associated X-ray temperature measurement (TX). This represents one of the largest samples of coherently derived cluster TX values to date. Our analysis of the X-ray observable to richness scaling relations has demonstrated that scatter in the TX–λ relation is roughly a third of that in the LX–λ relation, and that the LX–λ scatter is intrinsic, i.e. will not be significantly reduced with larger sample sizes. Analysis of the scaling relation between LX and TX has shown that the fits are sensitive to the selection method of the sample, i.e. whether the sample is made up of clusters detected ‘serendipitously’ compared to those deliberately targeted by XMM. These differences are also seen in the LX–λ relation and, to a lesser extent, in the TX–λ relation. Exclusion of the emission from the cluster core does not make a significant impact on the findings. A combination of selection biases is a likely, but yet unproven, reason for these differences. Finally, we have also used our data to probe recent claims of anisotropy in the LX–TX relation across the sky. We find no evidence of anistropy, but stress this may be masked in our analysis by the incomplete declination coverage of the SDSS.
Context.
High-precision pulsar timing requires accurate corrections for dispersive delays of radio waves, parametrized by the dispersion measure (DM), particularly if these delays are variable in ...time. In a previous paper, we studied the solar wind (SW) models used in pulsar timing to mitigate the excess of DM that is annually induced by the SW and found these to be insufficient for high-precision pulsar timing. Here we analyze additional pulsar datasets to further investigate which aspects of the SW models currently used in pulsar timing can be readily improved, and at what levels of timing precision SW mitigation is possible.
Aims.
Our goals are to verify: (a) whether the data are better described by a spherical model of the SW with a time-variable amplitude, rather than a time-invariant one as suggested in literature, and (b) whether a temporal trend of such a model’s amplitudes can be detected.
Methods.
We use the pulsar timing technique on low-frequency pulsar observations to estimate the DM and quantify how this value changes as the Earth moves around the Sun. Specifically, we monitor the DM in weekly to monthly observations of 14 pulsars taken with parts of the LOw-Frequency ARray (LOFAR) across time spans of up to 6 years. We develop an informed algorithm to separate the interstellar variations in the DM from those caused by the SW and demonstrate the functionality of this algorithm with extensive simulations. Assuming a spherically symmetric model for the SW density, we derive the amplitude of this model for each year of observations.
Results.
We show that a spherical model with a time-variable amplitude models the observations better than a spherical model with a constant amplitude, but that both approaches leave significant SW-induced delays uncorrected in a number of pulsars in the sample. The amplitude of the spherical model is found to be variable in time, as opposed to what has been previously suggested.
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