The goal of the Herschel open time key programme ``TNOs are Cool!'' is to derive the physical and thermal properties for a large sample of Centaurs and trans-Neptunian objects (TNOs), including ...resonant, classical, detached and scattered disk objects. We present results for seven targets either observed in PACS point-source, or in mini scan-map mode. Spitzer-MIPS observations were included for three objects. The sizes of these targets range from 100 km to almost 1000 km, five have low geometric albedos below 10%, (145480) 2005 TB190 has a higher albedo above 15%. Classical thermal models driven by an intermediate beaming factor of eta = 1.2 or eta-values adjusted to the observed colour temperature fit the multi-band observations well in most cases. More sophisticated thermophysical models give very similar diameter and albedo values for thermal inertias in the range 0-25 J m-2 s-0.5 K-1, consistent with very low heat conductivities at temperatures far away from the Sun. The early experience with observing and model strategies will allow us to derive physical and thermal properties for our complete Herschel TNO sample of 140 targets as a benchmark for understanding the solar system debris disk, and extra-solar ones as well.
High-resolution far-infrared and sub-millimetre spectroscopy of water lines is an important tool to understand the physical and chemical properties of cometary atmospheres. We present observations of ...several rotational ortho- and para-water transitions in comet C/2008 Q3 (Garradd) performed with HIFI on Herschel. These observations have provided the first detection of the 212–101 (1669 GHz) ortho and 111–000 (1113 GHz) para transitions of water in a cometary spectrum. In addition, the ground-state transition 110–101 at 557 GHz is detected and mapped. By detecting several water lines quasi-simultaneously and mapping their emission we can constrain the excitation parameters in the coma. Synthetic line profiles are computed using excitation models which include excitation by collisions, solar infrared radiation, and radiation trapping. We obtain the gas kinetic temperature, constrain the electron density profile, and estimate the coma expansion velocity by analyzing the map and line shapes. We derive water production rates of 1.7–2.8 × 1028 s-1 over the range rh = 1.83–1.85 AU.
Pulmonary hypertension (PH) is associated with structural remodeling of pulmonary arteries (PAs) because of excessive proliferation of fibroblasts, endothelial cells, and smooth muscle cells (SMCs). ...The peptide hormone angiotensin II (ANG II) contributes to pulmonary vascular remodeling, in part, through its ability to trigger extracellular signal-regulated kinase (ERK1/2) activation. Here, we demonstrate that the ERK1/2 phosphatase, dual-specificity phosphatase 5 (DUSP5), functions as a negative regulator of ANG II-mediated SMC proliferation and PH. In contrast to wild-type controls, Dusp5 null mice infused with ANG II developed PH and right ventricular (RV) hypertrophy. PH in Dusp5 null mice was associated with thickening of the medial layer of small PAs, suggesting an in vivo role for DUSP5 as a negative regulator of ANG II-dependent SMC proliferation. Consistent with this, overexpression of DUSP5 blocked ANG II-mediated proliferation of cultured human pulmonary artery SMCs (hPASMCs) derived from patients with idiopathic PH or from failed donor controls. Collectively, the data support a role for DUSP5 as a feedback inhibitor of ANG II-mediated ERK signaling and PASMC proliferation and suggest that disruption of this circuit leads to adverse cardiopulmonary remodeling.
Dual-specificity phosphatases (DUSPs) serve critical roles in the regulation of mitogen-activated protein kinases, but their functions in the cardiovascular system remain poorly defined. Here, we provide evidence that DUSP5, which resides in the nucleus and specifically dephosphorylates extracellular signal-regulated kinase (ERK1/2), blocks pulmonary vascular smooth muscle cell proliferation. In response to angiotensin II infusion, mice lacking DUSP5 develop pulmonary hypertension and right ventricular cardiac hypertrophy. These findings illustrate DUSP5-mediated suppression of ERK signaling in the lungs as a protective mechanism.
The goal of the Herschel open time key programme “TNOs are Cool!” is to derive the physical and thermal properties for a large sample of Centaurs and trans-Neptunian objects (TNOs), including ...resonant, classical, detached and scattered disk objects. We present results for seven targets either observed in PACS point-source, or in mini scan-map mode. Spitzer-MIPS observations were included for three objects. The sizes of these targets range from 100 km to almost 1000 km, five have low geometric albedos below 10%, (145480) 2005 TB190 has a higher albedo above 15%. Classical thermal models driven by an intermediate beaming factor of η = 1.2 or η-values adjusted to the observed colour temperature fit the multi-band observations well in most cases. More sophisticated thermophysical models give very similar diameter and albedo values for thermal inertias in the range 0–25 J m-2 s-0.5 K-1, consistent with very low heat conductivities at temperatures far away from the Sun. The early experience with observing and model strategies will allow us to derive physical and thermal properties for our complete Herschel TNO sample of 140 targets as a benchmark for understanding the solar system debris disk, and extra-solar ones as well.
The spatiotemporal regulation of the Ras/ERK pathway is critical in determining the physiological and pathophysiological outcome of signaling. Dual-specificity mitogen-activated protein kinase (MAPK) ...phosphatases (DUSPs or MKPs) are key regulators of pathway activity and may also localize ERK to distinct subcellular locations. Here we present methods largely based on the use of high content microscopy to both visualize and quantitate the subcellular distribution of activated (p-ERK) and total ERK in populations of mouse embryonic fibroblasts derived from mice lacking DUSP5, a nuclear ERK-specific MKP. Such methods in combination with rescue experiments using adenoviral vectors encoding wild-type and mutant forms of DUSP5 have allowed us to visualize specific defects in ERK regulation in these cells thus confirming the role of this phosphatase as both a nuclear regulator of ERK activity and localization.
Blazar OJ287 exhibits large thermal flares at least twice every 12 years. The times of these flares have been predicted successfully using the model of a quasi-Keplerian eccentric black hole binary ...where the secondary impacts the accretion disk of the primary, creating the thermal flares. New measurements of the historical light curve have been combined with the observations of the 2015 November/December flare to identify the impact record since year 1886, and to constrain the orbit of the binary. The orbital solution shows that the binary period, now 12.062 years, is decreasing at the rate of 36 days per century. This corresponds to an energy loss to gravitational waves that is 6.5 ± 4 % less than the rate predicted by the standard quadrupolar gravitational wave (GW) emission. We show that the difference is due to higher order gravitational radiation reaction terms that include the dominant order tail contributions.
The RAS–RAF–MEK–ERK pathway has been intensively studied in oncology, with RAS known to be mutated in ∼30% of all human cancers. The recent emergence of ERK1/2 inhibitors and their ongoing clinical ...investigation demands a better understanding of ERK1/2 behavior following small-molecule inhibition. Although fluorescent fusion proteins and fluorescent antibodies are well-established methods of visualizing proteins, we show that ERK1/2 can be visualized via a less-invasive approach based on a two-step process using inverse electron demand Diels–Alder cycloaddition. Our previously reported trans-cyclooctene-tagged covalent ERK1/2 inhibitor was used in a series of imaging experiments following a click reaction with a tetrazine-tagged fluorescent dye. Although limitations were encountered with this approach, endogenous ERK1/2 was successfully imaged in cells, and “on-target” staining was confirmed by over-expressing DUSP5, a nuclear ERK1/2 phosphatase that anchors ERK1/2 in the nucleus.
The D/H ratio in cometary water is believed to be an important indicator of the conditions under which icy planetesimals formed and can provide clues to the contribution of comets to the delivery of ...water and other volatiles to Earth. Available measurements suggest that there is isotopic diversity in the comet population. The Herschel Space Observatory revealed an ocean-like ratio in the Jupiter-family comet 103P/Hartley 2, whereas most values measured in Oort-cloud comets are twice as high as the ocean D/H ratio. We present here a new measurement of the D/H ratio in the water of an Oort-cloud comet. HDO, H2O, and \hbox{$\mathrm{H}_2^{18}\mathrm{O}$}H218O lines were observed with high signal-to-noise ratio in comet C/2009 P1 (Garradd) using the Herschel HIFI instrument. Spectral maps of two water lines were obtained to constrain the water excitation. The D/H ratio derived from the measured H216O and HDO production rates is (2.06 ± 0.22) × 10-4. This result shows that the D/H in the water of Oort-cloud comets is not as high as previously thought, at least for a fraction of the population, hence the paradigm of a single, archetypal D/H ratio for all Oort-cloud comets is no longer tenable. Nevertheless, the value measured in C/2009 P1 (Garradd) is significantly higher than the Earth’s ocean value of 1.558 × 10-4. The measured 16O/18O ratio of 523 ± 32 is, however, consistent with the terrestrial value.
We have obtained the first continuous disk averaged spectrum of Mars from 450 to 1550 Ghz using the Herschel-SPIRE Fourier-transform spectrometer. The spectrum was obtained at a constant resolution ...of 1.4 GHz across the whole band. The flux from the planet is such that the instrument was operated in “bright source” mode to prevent saturation of the detectors. This was the first successful use of this mode and in this work we describe the method used for observing Mars together with a detailed discussion of the data reduction techniques required to calibrate the spectrum. We discuss the calibration accuracy obtained and describe the first comparison with surface and atmospheric models. In addition to a direct photometric measurement of the planet the spectrum contains the characteristic transitions of 12CO from J 5–4 to J 13–12 as well as numerous H2O transitions. Together these allow the comparison to global atmospheric models allowing the mean mixing ratios of water and 12CO to be investigated. We find that it is possible to match the observed depth of the absorption features in the spectrum with a fixed water mixing ratio of 1×10-4 and a 12CO mixing ratio of 9×10-4.
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