Tyrosine kinase fusion oncogenes that occur as a result of chromosomal translocations have been shown to activate proliferative and antiapoptotic pathways in leukemic cells, but the importance of ...autocrine and paracrine expression of hematopoietic cytokines in leukemia pathogenesis is not understood. Evidence that leukemic transformation may be, at least in part, cytokine dependent includes data from primary human leukemia cells, cell culture experiments, and murine models of leukemia. This report demonstrates that interleukin (IL)-3 plasma levels are elevated in myeloproliferative disease (MPD) caused by the TEL/tyrosine kinase fusions TEL/platelet-derived growth factor beta receptor (PDGFβR), TEL/Janus kinase 2 (JAK2), and TEL/neurotrophin-3 receptor (TRKC). Plasma granulocyte-macrophage colony-stimulating factor (GM-CSF) levels were elevated by TEL/PDGFβR and TEL/JAK2. However, all of the fusions tested efficiently induced MPD in mice genetically deficient for both GM-CSF and IL-3, demonstrating that these cytokines are not necessary for the development of disease in this model system. Furthermore, in experiments using normal marrow transduced with TEL/PDGFβR retrovirus mixed with marrow transduced with an enhanced green fluorescent protein (EGFP) retrovirus, the MPD induced in these mice demonstrated minimal stimulation of normal myelopoiesis by the TEL/PDGFβR-expressing cells. In contrast, recipients of mixed GM-CSF–transduced and EGFP-transduced marrow exhibited significant paracrine expansion of EGFP-expressing cells. Collectively, these data demonstrate that, although cytokine levels are elevated in murine bone marrow transplant models of leukemia using tyrosine kinase fusion oncogenes, GM-CSF and IL-3 are not required for myeloproliferation by any of the oncogenes tested.
Radial velocity monitoring has revealed the presence of moving broad emission lines in some quasars, potentially indicating the presence of a sub-parsec binary system. Phase-referenced, near-infrared ...interferometric observations could map out the binary orbit by measuring the photocenter difference between a broad emission line and the hot dust continuum. We show that astrometric data over several years may be able to detect proper motions and accelerations, confirming the presence of a binary and constraining system parameters. The brightness, redshifts, and astrometric sizes of current candidates are well matched to the capabilities of the upgraded VLTI/GRAVITY+ instrument, and we identify a first sample of 10 possible candidates. The astrometric signature depends on the morphology and evolution of hot dust emission in supermassive black hole binary systems. Measurements of the photocenter offset may reveal binary motion whether the hot dust emission region is fixed to the inner edge of the circumbinary disk, or moves in response to the changing irradiation pattern from an accreting secondary black hole.
GRAVITY+ is the upgrade of GRAVITY and the Very Large Telescope Interferometer (VLTI) with wide-separation fringe tracking, new adaptive optics, and laser guide stars on all four 8~m Unit Telescopes ...(UTs), for ever fainter, all-sky, high contrast, milliarcsecond interferometry. Here we present the design and first results of the first phase of GRAVITY+, called GRAVITY Wide. GRAVITY Wide combines the dual-beam capabilities of the VLTI and the GRAVITY instrument to increase the maximum separation between the science target and the reference star from 2 arcseconds with the 8 m UTs up to several 10 arcseconds, limited only by the Earth's turbulent atmosphere. This increases the sky-coverage of GRAVITY by two orders of magnitude, opening up milliarcsecond resolution observations of faint objects, and in particular the extragalactic sky. The first observations in 2019 - 2022 include first infrared interferometry of two redshift \(z\sim2\) quasars, interferometric imaging on the binary system HD 105913A, and repeated observations of multiple star systems in the Orion Trapezium Cluster. We find the coherence loss between the science object and fringe-tracking reference star well described by the turbulence of the Earth's atmosphere. We confirm that the larger apertures of the UTs result in higher visibilities for a given separation due to larger overlap of the projected pupils on sky and give predictions for visibility loss as a function of separation to be used for future planning.
Large-amplitude Sgr A* near-infrared flares result from energy injection into electrons near the black hole event horizon. Astrometry data show continuous rotation of the emission region during ...bright flares, and corresponding rotation of the linear polarization angle. One broad class of physical flare models invokes magnetic reconnection. Here we show that such a scenario can arise in a general relativistic magnetohydrodynamic simulation of a magnetically arrested disc. Saturation of magnetic flux triggers eruption events, where magnetically dominated plasma is expelled from near the horizon and forms a rotating, spiral structure. Dissipation occurs via reconnection at the interface of the magnetically dominated plasma and surrounding fluid. This dissipation is associated with large increases in near-infrared emission in models of Sgr A*, with durations and amplitudes consistent with the observed flares. Such events occur at roughly the timescale to re-accumulate the magnetic flux from the inner accretion disc, 10h for Sgr A*. We study near-infrared observables from one sample event to show that the emission morphology tracks the boundary of the magnetically dominated region. As the region rotates around the black hole, the near-infrared centroid and linear polarization angle both undergo continuous rotation, similar to the behavior seen in Sgr A* flares.
The centre of our Galaxy is by far the closest galactic nucleus to theEarth. Not surprisingly, Sgr A*, the super-massive black hole candidate lyingat its gravitational centre, is the black hole (BH) ...candidate which offersthe best spatial resolution in terms of Schwarzschild radius tpRs, thanksto the good compromise between its mass (≃3.6×106 M⊙)and distance (≃8 kpc). For a 3.6×106 M⊙ BH,tpRs=14 R⊙ (≃8 umuas at 8 kpc). This is still twoorders of magnitudes smaller than the spatial resolution offered by theVLTI, but it is the right scale for studies involving only astrometry withPRIMA. We will show how this property can be used to tremendously improvethe knowledge of the central mass distribution, constrain the properties ofthe BH, and even directly probe the space-time around this object.
These protoplanetary disks in T Tauri stars play a central role in star and planet formation. We spatially resolve at sub-au scales the innermost regions of a sample of T Tauri's disks to better ...understand their morphology and composition. We extended our homogeneous data set of 27 Herbig stars and collected near-IR K-band observations of 17 T Tauri stars, spanning effective temperatures and luminosities in the ranges of ~4000-6000 K and ~0.4-10 Lsun. We focus on the continuum emission and develop semi-physical geometrical models to fit the interferometric data and search for trends between the properties of the disk and the central star. The best-fit models of the disk's inner rim correspond to wide rings. We extend the Radius-luminosity relation toward the smallest luminosities (0.4-10 Lsun) and find the R~L^(1/2) trend is no longer valid, since the K-band sizes measured with GRAVITY are larger than the predicted sizes from sublimation radius computation. No clear correlation between the K-band half-flux radius and the mass accretion rate is seen. Having magnetic truncation radii in agreement with the K-band GRAVITY sizes would require magnetic fields as strong as a few kG, which should have been detected, suggesting that accretion is not the main process governing the location of the half-flux radius of the inner dusty disk. Our measurements agree with models that take into account the scattered light. The N-to-K band size ratio may be a proxy for disentangling disks with silicate features in emission from disks with weak and/or in absorption silicate features. When comparing inclinations and PA of the inner disks to those of the outer disks (ALMA) in nine objects of our sample, we detect misalignments for four objects.
The diffuse Extragalactic Background Light (EBL) contains unique information about the epochs of formation and the history of evolution of galaxies. Unfortunately, direct measurements are subject to ...large systematic uncertainties due to the difficulties in the accurate model-based subtraction of the bright foregrounds. An alternative approach is based on the detection and identification of EBL absorption features in high-energy spectra of objects of known redshift. Here we exploit this method on the blazars H 2356-309 (z=0.165) and 1ES 1101-232 (z=0.186), newly discovered at TeV energies by the H.E.S.S. Collaboration. They are the most distant sources with measured spectra known so far at these energies. Their hard spectra provide the most stringent upper limit to date on the EBL in the Opt--NIR band, which appears significantly lower than expected from the current "direct" estimates and very close to the absolute lower limit represented by the integrated light of resolved galaxies. In addition to important cosmological implications, this result shows that the intergalactic space is more transparent to gamma-rays than previously thought, expanding the horizon of the TeV Universe.
We report on a survey of the inner part of the Galactic Plane in very high energy gamma-rays, with the H.E.S.S. Cherenkov telescope system. The Galactic Plane between +-30deg in longitude and +-3deg ...in latitude relative to the Galactic Centre was observed in 500 pointings for a total of 230 hours, reaching an average flux sensitivity of 2% of the Crab Nebula at energies above 200 GeV. Fourteen previously unknown sources were detected at a significance level greater than 4 sigma after accounting for all trials involved in the search. Initial results on the eight most significant of these sources were already reported elsewhere. Here we present detailed spectral and morphological information for all the new sources, along with a discussion on possible counterparts in other wavelength bands. The distribution in Galactic latitude of the detected sources appears to be consistent with a scale height in the Galactic disk for the parent population smaller than 100 pc, consistent with expectations for supernova remnants and/or pulsar wind nebulae.
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