In men with prostate cancer on PSA screening, radical treatments led to half the incidence of metastasis and local progression as active monitoring without affecting disease-specific or overall ...survival.
NUT midline carcinoma (NMC) is an aggressive type of squamous cell carcinoma that is defined by the presence of BRD-NUT fusion oncogenes, which encode chimeric proteins that block differentiation and ...maintain tumor growth. BRD-NUT oncoproteins contain two bromodomains whose binding to acetylated histones is required for the blockade of differentiation in NMC, but the mechanisms by which BRD-NUT act remain uncertain. Here, we provide evidence that MYC is a key downstream target of BRD4-NUT. Expression profiling of NMCs shows that the set of genes whose expression is maintained by BRD4-NUT is highly enriched for MYC upregulated genes, and MYC and BRD4-NUT protein expression is strongly correlated in primary NMCs. More directly, we find that BRD4-NUT associates with the MYC promoter and is required to maintain MYC expression in NMC cell lines. Moreover, both siRNA knockdown of MYC and a dominant-negative form of MYC, omomyc, induce differentiation of NMC cells. Conversely, differentiation of NMC cells induced by knockdown of BRD4-NUT is abrogated by enforced expression of MYC. Together, these findings suggest that MYC is a downstream target of BRD4-NUT that is required for maintenance of NMC cells in an undifferentiated, proliferative state. Our findings support a model in which dysregulation of MYC by BRD-NUT fusion proteins has a central role in the pathogenesis of NMC.
During the past several decades, there has been a steady increase in the frequency of opportunistic invasive fungal infections (IFIs) in immunocompromised patients. However, there is substantial ...controversy concerning optimal diagnostic criteria for these IFIs. Therefore, members of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group formed a consensus committee to develop standard definitions for IFIs for clinical research. On the basis of a review of literature and an international consensus, a set of research-oriented definitions for the IFIs most often seen and studied in immunocompromised patients with cancer is proposed. Three levels of probability are proposed: "proven," "probable," and "possible." The definitions are intended for use in the context of clinical and/or epidemiological research, not for clinical decision making.
The Southern Parkes Large-Area Survey in Hydroxyl (SPLASH) is a sensitive, unbiased, and fully sampled survey of the southern Galactic plane and Galactic Centre in all four ground-state transitions ...of the hydroxyl (OH) radical. The survey provides a deep census of 1612-, 1665-, 1667-, and 1720-MHz OH absorption and emission from the Galactic interstellar medium, and is also an unbiased search for maser sources in these transitions. We present here first results from the SPLASH pilot region, which covers Galactic longitudes 334° to 344° and latitudes ±2°. Diffuse OH is widely detected in all four transitions, with optical depths that are always small (averaged over the Parkes beam), and with departures from local thermodynamic equilibrium common even in the 1665- and 1667-MHz main lines. To a 3σ sensitivity of ∼30 mK, we find no evidence of OH envelopes extending beyond the CO-bright regions of molecular cloud complexes, and conclude that the similarity of the OH excitation temperature and the level of the continuum background is at least partly responsible for this. We detect masers and maser candidates in all four transitions, approximately 50 per cent of which are new detections. This implies that SPLASH will produce a substantial increase in the known population of ground-state OH masers in the southern Galactic plane.
Voriconazole, a triazole antifungal agent, demonstrates wide interpatient variability in serum concentrations, due in part to variant CYP2C19 alleles. Individuals who are CYP2C19 ultrarapid ...metabolizers have decreased trough voriconazole concentrations, delaying achievement of target blood concentrations; whereas poor metabolizers have increased trough concentrations and are at increased risk of adverse drug events. We summarize evidence from the literature supporting this association and provide therapeutic recommendations for the use of voriconazole for treatment based on CYP2C19 genotype (updates at https://cpicpgx.org/guidelines/ and www.pharmgkb.org).
ABSTRACT G0.253+0.016 is a molecular clump that appears to be on the verge of forming a high-mass cluster: its extremely low dust temperature, high mass, and high density, combined with its lack of ...prevalent star formation, make it an excellent candidate for an Arches-like cluster in a very early stage of formation. Here we present new Atacama Large Millimeter/Sub-millimeter Array observations of its small-scale (∼0.07 pc) 3 mm dust continuum and molecular line emission from 17 different species that probe a range of distinct physical and chemical conditions. The data reveal a complex network of emission features with a complicated velocity structure: there is emission on all spatial scales, the morphology of which ranges from small, compact regions to extended, filamentary structures that are seen in both emission and absorption. The dust column density is well traced by molecules with higher excitation energies and critical densities, consistent with a clump that has a denser interior. A statistical analysis supports the idea that turbulence shapes the observed gas structure within G0.253+0.016. We find a clear break in the turbulent power spectrum derived from the optically thin dust continuum emission at a spatial scale of ∼0.1 pc, which may correspond to the spatial scale at which gravity has overcome the thermal pressure. We suggest that G0.253+0.016 is on the verge of forming a cluster from hierarchical, filamentary structures that arise from a highly turbulent medium. Although the stellar distribution within high-mass Arches-like clusters is compact, centrally condensed, and smooth, the observed gas distribution within G0.253+0.016 is extended, with no high-mass central concentration, and has a complex, hierarchical structure. If this clump gives rise to a high-mass cluster and its stars are formed from this initially hierarchical gas structure, then the resulting cluster must evolve into a centrally condensed structure via a dynamical process.
Despite the simplicity of theoretical models of supersonically turbulent, isothermal media, their predictions successfully match the observed gas structure and star formation activity within ...low-pressure (P/k < 10 super(5) K cm super(-3)) molecular clouds in the solar neighborhood. However, it is unknown whether or not these theories extend to clouds in high-pressure (P/k > 10 super(7)K cm super(-3)) environments, like those in the Galaxy's inner 200 pc central molecular zone (CMZ) and in the early universe. Here, we present Atacama Large Millimeter/submillimeter Array 3 mm dust continuum emission within a cloud, GO.253+0.016, which is immersed in the high-pressure environment of the CMZ. While the log-normal shape and dispersion of its column density probability distribution function (PDF) are strikingly similar to those of solar neighborhood clouds, there is one important quantitative difference: its mean column density is one to two orders of magnitude higher. Both the similarity and difference in the PDF compared to those derived from solar neighborhood clouds match predictions of turbulent cloud models given the high-pressure environment of the CMZ. The PDF shows a small deviation from log-normal at high column densities confirming the youth of GO.253+0.016. Its lack of star formation is consistent with the theoretically predicted, environmentally dependent volume density threshold for star formation which is orders of magnitude higher than that derived for solar neighborhood clouds. Our results provide the first empirical evidence that the current theoretical understanding of molecular cloud structure derived from the solar neighborhood also holds in high-pressure environments. We therefore suggest that these theories may be applicable to understand star formation in the early universe.
ABSTRACT Star formation is primarily controlled by the interplay between gravity, turbulence, and magnetic fields. However, the turbulence and magnetic fields in molecular clouds near the Galactic ...center may differ substantially compared to spiral-arm clouds. Here we determine the physical parameters of the central molecular zone (CMZ) cloud G0.253+0.016, its turbulence, magnetic field, and filamentary structure. Using column density maps based on dust-continuum emission observations with ALMA+Herschel, we identify filaments and show that at least one dense core is located along them. We measure the filament width and the sonic scale of the turbulence, and find . A strong velocity gradient is seen in the HNCO intensity-weighted velocity maps obtained with ALMA+Mopra. The gradient is likely caused by large-scale shearing of G0.253+0.016, producing a wide double-peaked velocity probability distribution function (PDF). After subtracting the gradient to isolate the turbulent motions, we find a nearly Gaussian velocity PDF typical for turbulence. We measure the total and turbulent velocity dispersion, and , respectively. Using magnetohydrodynamical turbulence simulations, we find that G0.253+0.016's turbulent magnetic field is only of the ordered field component. Combining these measurements, we reconstruct the dominant turbulence driving mode in G0.253+0.016 and find a driving parameter of , indicating solenoidal (divergence-free) driving. We compare this to spiral-arm clouds, which typically have a significant compressive (curl-free) driving component ( ). Motivated by previous reports of strong shearing motions in the CMZ, we speculate that shear causes the solenoidal driving in G0.253+0.016 and show that this reduces the star-formation rate by a factor of 6.9 compared to typical nearby clouds.
The Solar Orbiter magnetometer Horbury, T. S.; O’Brien, H.; Carrasco Blazquez, I. ...
Astronomy and astrophysics (Berlin),
10/2020, Letnik:
642
Journal Article
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The magnetometer instrument on the Solar Orbiter mission is designed to measure the magnetic field local to the spacecraft continuously for the entire mission duration. The need to characterise not ...only the background magnetic field but also its variations on scales from far above to well below the proton gyroscale result in challenging requirements on stability, precision, and noise, as well as magnetic and operational limitations on both the spacecraft and other instruments. The challenging vibration and thermal environment has led to significant development of the mechanical sensor design. The overall instrument design, performance, data products, and operational strategy are described.
We have conducted a Galactic plane survey of methanol masers at 6668 MHz using a seven-beam receiver on the Parkes telescope. Here we present results from the first part, which provides sensitive ...unbiased coverage of a large region around the Galactic Centre. Details are given for 183 methanol maser sites in the longitude range 345° through the Galactic Centre to 6°. Within 6° of the Galactic Centre, we found 88 maser sites, of which more than half (48) are new discoveries. The masers are confined to a narrow Galactic latitude range, indicative of many sources at the Galactic Centre distance and beyond, and confined to a thin disc population; there is no high-latitude population that might be ascribed to the Galactic bulge. Within 2° of the Galactic Centre the maser velocities all lie between −60 and +77 km s−1, a range much smaller than the 540 km s−1 range observed in CO. Elsewhere, the maser with highest positive velocity (+107 km s−1) occurs, surprisingly, near longitude 355° and is probably attributable to the Galactic bar. The maser with the most negative velocity (−127 km s−1) is near longitude 346°, within the longitude–velocity locus of the near side of the ‘3-kpc arm’. It has the most extreme velocity of a clear population of masers associated with the near and far sides of the 3-kpc arm. Closer to the Galactic Centre the maser space density is generally low, except within 0.25 kpc of the Galactic Centre itself, the ‘Galactic Centre zone’, where it is 50 times higher, which is hinted at by the longitude distribution, and confirmed by the unusual velocities.
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