Messier 87 (M 87) is one of the nearest radio galaxies with a prominent jet extending from sub-pc to kpc scales. Because of its proximity and the large mass of its central black hole (BH), it is one ...of the best radio sources for the study of jet formation. We study the physical conditions near the jet base at projected separations from the BH of ~7–100 Schwarzschild radii (Rsch). Global mm-VLBI Array (GMVA) observations at 86 GHz (λ = 3.5 mm) provide an angular resolution of ~50 μas, which corresponds to a spatial resolution of only 7 Rsch and reach the small spatial scale. We use five GMVA data sets of M 87 obtained from 2004 to 2015 and present new high angular resolution VLBI maps at 86 GHz. In particular, we focus on the analysis of the brightness temperature, the jet ridge lines, and the ratio of jet to counter-jet. The imaging reveals a parabolically expanding limb-brightened jet which emanates from a resolved VLBI core of ~(8–13) Rsch in size. The observed brightness temperature of the core at any epoch is ~(1–3) × 1010 K, which is below the equipartition brightness temperature and suggests magnetic energy dominance at the jet base. We estimate the diameter of the jet at its base to be ~5 Rsch assuming a self-similar jet structure. This suggests that the sheath of the jet may be anchored in the very inner portion of the accretion disk. The image stacking reveals faint emission at the center of the edge-brightened jet on sub-pc scales. We discuss its physical implication within the context of the spine-sheath structure of the jet.
Summary Objective Disruptions of extracellular matrix (ECM) homeostasis are key events in the pathogenesis of osteoarthritis (OA). MicroRNA-140 (miRNA-140) is expressed specifically in cartilage and ...regulates ECM-degrading enzymes. Our objective in this study was to determine if intra-articular injection of miRNA-140 can attenuate OA progression in rats. Design miRNA-140 levels in human normal and OA cartilage derived chondrocytes and synovial fluid were assessed by polymerase chain reaction (PCR). After primary human chondrocytes were transfected with miRNA-140 mimic or inhibitor, PCR and western blotting were performed to quantify Collagen II, MMP-13, and ADAMTS-5 expression. An OA model was induced surgically in rats, and subsequently treated with one single intra-articular injection of miRNA-140 agomir. At 4, 8, and 12 weeks after surgery, OA progression were evaluated macroscopically, histologically, and immunohistochemically in these rats. Results miRNA-140 levels were significantly reduced in human OA cartilage derived chondrocytes and synovial fluid compared with normal chondrocytes and synovial fluid. Overexpressing miRNA-140 in primary human chondrocytes promoted Collagen II expression and inhibited MMP-13 and ADAMTS-5 expression. miRNA-140 levels in rat cartilage were significantly higher in the miRNA-140 agomir group than in the control group. Moreover, behavioural scores, chondrocyte numbers, cartilage thickness and Collagen II expression levels in cartilage were significantly higher, while pathological scores and MMP-13 and ADAMTS-5 expression levels were significantly lower in the miRNA-140 agomir group than in the control group. Conclusion Intra-articular injection of miRNA-140 can alleviate OA progression by modulating ECM homeostasis in rats, and may have potential as a new therapy for OA.
We report results from a deep polarization imaging of the nearby radio galaxy 3C 84 (NGC 1275). The source was observed with the Global Millimeter VLBI Array (GMVA) at 86 GHz at an ultrahigh angular ...resolution of 50 μas (corresponding to ∼200Rs). We also add complementary multiwavelength data from the Very Long Baseline Array (VLBA; 15 and 43 GHz) and from the Atacama Large Millimeter/submillimeter Array (ALMA; 97.5, 233.0 and 343.5 GHz). At 86 GHz, we measured a fractional linear polarization of ∼2% in the VLBI core region. The polarization morphology suggests that the emission is associated with an underlying limb-brightened jet. The fractional linear polarization is lower at 43 and 15 GHz (∼0.3−0.7% and <0.1%, respectively). This suggests an increasing linear polarization degree toward shorter wavelengths on VLBI scales. We also obtain a large rotation measure (RM) of ∼105–6 rad m2 in the core at ≳43 GHz. Moreover, the VLBA 43 GHz observations show a variable RM in the VLBI core region during a small flare in 2015. Faraday depolarization and Faraday conversion in an inhomogeneous and mildly relativistic plasma could explain the observed linear polarization characteristics and the previously measured frequency dependence of the circular polarization. Our Faraday depolarization modeling suggests that the RM most likely originates from an external screen with a highly uniform RM distribution. To explain the large RM value, the uniform RM distribution and the RM variability, we suggest that the Faraday rotation is caused by a boundary layer in a transversely stratified jet. Based on the RM and the synchrotron spectrum of the core, we provide an estimate for the magnetic field strength and the electron density of the jet plasma.
Searching for space-time variations of the constants of Nature is a promising way to search for new physics beyond general relativity and the standard model motivated by unification theories and ...models of dark matter and dark energy. We propose a new way to search for a variation of the fine-structure constant using measurements of late-type evolved giant stars from the S star cluster orbiting the supermassive black hole in our Galactic Center. A measurement of the difference between distinct absorption lines (with different sensitivity to the fine structure constant) from a star leads to a direct estimate of a variation of the fine structure constant between the star's location and Earth. Using spectroscopic measurements of five stars, we obtain a constraint on the relative variation of the fine structure constant below 10^{-5}. This is the first time a varying constant of nature is searched for around a black hole and in a high gravitational potential. This analysis shows new ways the monitoring of stars in the Galactic Center can be used to probe fundamental physics.
Palbociclib and Letrozole in Advanced Breast Cancer Finn, Richard S; Martin, Miguel; Rugo, Hope S ...
New England journal of medicine/The New England journal of medicine,
11/2016, Letnik:
375, Številka:
20
Journal Article
Recenzirano
Odprti dostop
Among women with previously untreated hormone-receptor–positive advanced breast cancer, the addition of the cyclin-dependent kinase inhibitor palbociclib to letrozole therapy resulted in longer ...progression-free survival than that with letrozole alone.
Hormone-receptor–positive breast cancer represents the largest therapeutic subtype of the disease, accounting for 60 to 65% of all malignant neoplasms of the breast. For more than 50 years, the treatment of hormone-receptor–positive disease has been focused on targeting the estrogen-receptor signaling pathway.
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However, both new and acquired resistance to hormonal blockade occurs in a large subset of these cancers, and new approaches are needed.
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The cyclin-dependent kinases (CDKs) are a large family of serine–threonine kinases that play an important role in regulating cell-cycle progression. The interaction of cyclin D with CDK4 and CDK6 facilitates the hyperphosphorylation of the retinoblastoma (Rb) . . .
DNA damage triggers diverse cancers, particularly hepatocellular carcinoma (HCC), but the intrinsic link between DNA damage and tumorigenesis remains unclear. Because of its role as an epigenetic and ...transcriptional regulator, histone deacetylase 3 (HDAC3) is essential for DNA damage control and is often aberrantly expressed in human HCC. In this study, we used individual class I HDAC member-deficient mice to demonstrate that K9 in histone H3 (H3K9), which is the critical site for the assembly of DNA damage response complexes, is exclusively targeted by HDAC3. Ablation of HDAC3 disrupted the deacetylation and consequent trimethylation of H3K9 (H3K9me3), the first step in double-strand break repair, and led to the accumulation of damaged DNA. Simultaneously, hyperacetylated H3K9 (H3K9ac) served as a transcriptional activator and enhanced multiple signaling pathways to promote tumorigenesis. Together, these results show that HDAC3 targets the H3K9ac/H3K9me3 transition to serve as a critical regulator that controls both DNA damage repair and the transcription of many tumor-related genes. Moreover, these findings provide novel insights into the link between DNA damage and transcriptional reprogramming in tumorigenesis. SIGNIFICANCE: These findings show that HDAC3 exclusively regulates H3K9ac in response to DNA damage, and loss of HDAC3 activity shifts the balance from DNA damage control to protumorigenic transcriptional activity.
Abstract There are expected to be ∼10 8 isolated black holes (BHs) in the Milky Way. OGLE-2011-BLG-0462/MOA-2011-BLG-191 (OB110462) is the only such BH with a mass measurement to date. However, its ...mass is disputed: Lam et al. measured a lower mass of 1.6–4.4 M ⊙ , while Sahu et al. and Mróz et al. measured a higher mass of 5.8–8.7 M ⊙ . We reanalyze OB110462, including new data from the Hubble Space Telescope (HST) and rereduced Optical Gravitational Lensing Experiment (OGLE) photometry. We also rereduce and reanalyze the HST data set with newly available software. We find significantly different (∼1 mas) HST astrometry than Lam et al. in the unmagnified epochs due to the amount of positional bias induced by a bright star ∼0.″4 from OB110462. After modeling the updated photometric and astrometric data sets, we find the lens of OB110462 is a 6.0 − 1.0 + 1.2 M ⊙ BH. Future observations with the Nancy Grace Roman Space Telescope, which will have an astrometric precision comparable or better to HST but a field of view 100× larger, will be able to measure hundreds of isolated BH masses via microlensing. This will enable the measurement of the BH mass distribution and improve understanding of massive stellar evolution and BH formation channels.
Stars with short orbital periods at the center of our Galaxy offer a powerful probe of a supermassive black hole. Over the past 17 years, the W. M. Keck Observatory has been used to image the ...galactic center at the highest angular resolution possible today. By adding to this data set and advancing methodologies, we have detected S0-102, a star orbiting our Galaxy's supermassive black hole with a period of just 11.5 years. S0-102 doubles the number of known stars with full phase coverage and periods of less than 20 years. It thereby provides the opportunity, with future measurements, to resolve degeneracies in the parameters describing the central gravitational potential and to test Einstein's theory of general relativity in an unexplored regime.
The supermassive black hole at the center of the Milky Way plays host to a massive, young cluster that may have formed in one of the most inhospitable environments in the Galaxy. We present new ...measurements of the global properties of this cluster, including the initial mass function (IMF), age, and cluster mass. These results are based on Keck laser-guide-star adaptive optics observations used to identify the young stars and measure their K p-band luminosity function as presented in Do et al. The exact age of the cluster is difficult to determine since our results show two distinct age solutions (3.9 Myr and 2.8 Myr) due to model degeneracies in the relative number of Wolf-Rayet and OB stars. The young cluster at the Galactic center is one of the few definitive examples of an IMF that deviates significantly from the near-universal IMFs found in the solar neighborhood.
We present new proper motions from the 10 m Keck telescopes for a puzzling population of massive, young stars located within 35 (0.14 pc) of the supermassive black hole at the Galactic center. Our ...proper motion measurements have uncertainties of only 0.07 mas yr-1 (3 km s-1), which is 7 times better than previous proper motion measurements for these stars, and enables us to measure accelerations as low as 0.2 mas yr-2 (7 km s-1 yr-1). Using these measurements, line-of-sight velocities from the literature, and three-dimensional velocities for additional young stars in the central parsec, we constrain the true orbit of each individual star and directly test the hypothesis that the massive stars reside in two stellar disks as has been previously proposed. Analysis of the stellar orbits reveals only one of the previously proposed disks of young stars using a method that is capable of detecting disks containing at least seven stars. The detected disk contains 50% of the young stars, is inclined by ~115° from the plane of the sky, and is oriented at a position angle of ~100° east of north. Additionally, the on-disk and off-disk populations have similar K-band luminosity functions and radial distributions that decrease at larger radii as r -2. The disk has an out-of-the-disk velocity dispersion of 28 ± 6 km s-1, which corresponds to a half-opening angle of 7° ± 2°, and several candidate disk members have eccentricities greater than 0.2. Our findings suggest that the young stars may have formed in situ but in a more complex geometry than a simple, thin circular disk.
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