Contribution of Underlying Connective Tissue Cells to Taste Buds in Mouse Tongue and Soft Palate

Taste buds, the sensory organs for taste, have been described as arising solely from the surrounding epithelium, which is in distinction from other sensory receptors that are known to originate from neural precursors, i.e., neural ectoderm that includes neural crest (NC). Our previous study suggested a potential contribution of NC derived cells to early immature fungiform taste buds in late embryonic (E18.5) and young postnatal (P1-10) mice. In the present study we demonstrated the contribution of the underlying connective tissue (CT) to mature taste buds in mouse tongue and soft palate. Three independent mouse models were used for fate mapping of NC and NC derived connective tissue cells: (1) P0-Cre/R26-tdTomato (RFP) to label NC, NC derived Schwann cells and derivatives; (2) Dermo1-Cre/RFP to label mesenchymal cells and derivatives; and (3) Vimentin-CreER/mGFP to label Vimentin-expressing CT cells and derivatives upon tamoxifen treatment. Both P0-Cre/RFP and Dermo1-Cre/RFP labeled cells were abundant in mature taste buds in lingual taste papillae and soft palate, but not in the surrounding epithelial cells. Concurrently, labeled cells were extensively distributed in the underlying CT. RFP signals were seen in the majority of taste buds and all three types (I, II, III) of differentiated taste bud cells, with the neuronal-like type III cells labeled at a greater proportion. Further, Vimentin-CreER labeled cells were found in the taste buds of 3-month-old mice whereas Vimentin immunoreactivity was only seen in the CT. Taken together, our data demonstrate a previously unrecognized origin of taste bud cells from the underlying CT, a conceptually new finding in our knowledge of taste bud cell derivation, i.e., from both the surrounding epithelium and the underlying CT that is primarily derived from NC

Calibration of the NuSTAR High Energy Focusing X-ray Telescope

We present the calibration of the \textit{Nuclear Spectroscopic Telescope Array} (\nustar) X-ray satellite. We used the Crab as the primary effective area calibrator and constructed a piece-wise linear spline function to modify the vignetting response. The achieved residuals for all off-axis angles and energies, compared to the assumed spectrum, are typically better than $\pm 2$\% up to 40\,keV and 5--10\,\% above due to limited counting statistics. An empirical adjustment to the theoretical 2D point spread function (PSF) was found using several strong point sources, and no increase of the PSF half power diameter (HPD) has been observed since the beginning of the mission. We report on the detector gain calibration, good to 60\,eV for all grades, and discuss the timing capabilities of the observatory, which has an absolute timing of $\pm$ 3\,ms. Finally we present cross-calibration results from two campaigns between all the major concurrent X-ray observatories (\textit{Chandra}, \textit{Swift}, \textit{Suzaku} and \textit{XMM-Newton}), conducted in 2012 and 2013 on the sources 3C\,273 and PKS\,2155-304, and show that the differences in measured flux is within $\sim$10\% for all instruments with respect to \nustar

NuSTAR Spectroscopy of Multi-Component X-ray Reflection from NGC 1068

We report on observations of NGC1068 with NuSTAR, which provide the best constraints to date on its $>10$~keV spectral shape. We find no strong variability over the past two decades, consistent with its Compton-thick AGN classification. The combined NuSTAR, Chandra, XMM-Newton, and Swift-BAT spectral dataset offers new insights into the complex reflected emission. The critical combination of the high signal-to-noise NuSTAR data and a spatial decomposition with Chandra allow us to break several model degeneracies and greatly aid physical interpretation. When modeled as a monolithic (i.e., a single N_H) reflector, none of the common Compton-reflection models are able to match the neutral fluorescence lines and broad spectral shape of the Compton reflection. A multi-component reflector with three distinct column densities (e.g., N_H~1.5e23, 5e24, and 1e25 cm^{-2}) provides a more reasonable fit to the spectral lines and Compton hump, with near-solar Fe abundances. In this model, the higher N_H components provide the bulk of the Compton hump flux while the lower N_H component produces much of the line emission, effectively decoupling two key features of Compton reflection. We note that ~30% of the neutral Fe Kalpha line flux arises from >2" (~140 pc), implying that a significant fraction of the <10 keV reflected component arises from regions well outside of a parsec-scale torus. These results likely have ramifications for the interpretation of poorer signal-to-noise observations and/or more distant objects [Abridged].Comment: Submitted to ApJ; 23 pages (ApJ format); 11 figures and 3 tables; Comments welcomed

Large-area Si(Li) Detectors for X-ray Spectrometry and Particle Tracking for the GAPS Experiment

Large-area lithium-drifted silicon (Si(Li)) detectors, operable 150{\deg}C above liquid nitrogen temperature, have been developed for the General Antiparticle Spectrometer (GAPS) balloon mission and will form the first such system to operate in space. These 10 cm-diameter, 2.5 mm-thick multi-strip detectors have been verified in the lab to provide <4 keV FWHM energy resolution for X-rays as well as tracking capability for charged particles, while operating in conditions (~-40{\deg}C and ~1 Pa) achievable on a long-duration balloon mission with a large detector payload. These characteristics enable the GAPS silicon tracker system to identify cosmic antinuclei via a novel technique based on exotic atom formation, de-excitation, and annihilation. Production and large-scale calibration of ~1000 detectors has begun for the first GAPS flight, scheduled for late 2021. The detectors developed for GAPS may also have other applications, for example in heavy nuclei identification

Peering through the Dust: NuSTAR Observations of Two FIRST-2MASS Red Quasars

Some reddened quasars appear to be transitional objects in the merger-induced black hole growth/galaxy evolution paradigm, where a heavily obscured nucleus starts to be unveiled by powerful quasar winds evacuating the surrounding cocoon of dust and gas. Hard X-ray observations are able to peer through this gas and dust, revealing the properties of circumnuclear obscuration. Here, we present NuSTAR and XMM-Newton/Chandra observations of FIRST-2MASS selected red quasars F2M 0830+3759 and F2M 1227+3214. We find that though F2M 0830+3759 is moderately obscured (N_(H,Z) = 2.1 ± 0.2 × 10^(22) cm^(−2)) and F2M 1227+3214 is mildly absorbed (N_(H,Z) = 3.4^(+0.8)_(−0.7) × 10^(21) cm^(−2)) along the line-of-sight, heavier global obscuration may be present in both sources, with N_(H,S) = 3.7^(+4.1)_(−2.6) × 10^(23) cm^(−2) and < 5.5 × 10^(23) cm^(−2), for F2M 0830+3759 and F2M 1227+3214, respectively. F2M 0830+3759 also has an excess of soft X-ray emission below 1 keV which is well accommodated by a model where 7% of the intrinsic AGN X-ray emission is scattered into the line-of-sight. While F2M 1227+3214 has a dust-to-gas ratio (E(B − V )/N_H) consistent with the Galactic value, the E(B−V )/NH value for F2M 0830+3759 is lower than the Galactic standard, consistent with the paradigm that the dust resides on galactic scales while the X-ray reprocessing gas originates within the dust-sublimation zone of the broad-line-region. The X-ray and 6.1μm luminosities of these red quasars are consistent with the empirical relations derived for high-luminosity, unobscured quasars, extending the parameter space of obscured AGN previously observed by NuSTAR to higher luminosities

3C 273 with NuSTAR: Unveiling the Active Galactic Nucleus

We present results from a 244 ks NuSTAR observation of 3C 273 obtained during a cross-calibration campaign with the Chandra, INTEGRAL, Suzaku, Swift, and XMM-Newton observatories. We show that the spectrum, when fit with a power-law model using data from all observatories except INTEGRAL over the 1–78 keV band, leaves significant residuals in the NuSTAR data between 30 and 78 keV. The NuSTAR 3–78 keV spectrum is well described by an exponentially cutoff power law (Γ = 1.646 ± 0.006, E_(cutoff) = 202_(-34)^(+51) keV) with a weak reflection component from cold, dense material. There is also evidence for a weak (EW = 23 ± 11 eV) neutral iron line. We interpret these features as arising from coronal emission plus reflection off an accretion disk or distant material. Beyond 80 keV INTEGRAL data show clear excess flux relative to an extrapolation of the active galactic nucleus model fit to NuSTAR. This high-energy power law is consistent with the presence of a beamed jet, which begins to dominate over emission from the inner accretion flow at 30–40 keV. Modeling the jet locally (in the NuSTAR + INTEGRAL band) as a power law, we find that the coronal component is fit by Γ_(AGN) = 1.638 ± 0.045, E_(cutoff) = 47 ± 15 keV, and jet photon index by Γ_(jet) = 1.05 ± 0.4. We also consider Fermi/LAT observations of 3C 273, and here the broadband spectrum of the jet can be described by a log-parabolic model, peaking at ~2 MeV. Finally, we investigate the spectral variability in the NuSTAR band and find an inverse correlation between flux and Γ

The variable hard x-ray emission of NGC 4945 as observed by NUSTAR

We present a broadband (~0.5-79 keV) spectral and temporal analysis of multiple NuSTAR observations combined with archival Suzaku and Chandra data of NGC4945, the brightest extragalactic source at 100 keV. We observe hard X-ray (> 10 keV) flux and spectral variability, with flux variations of a factor 2 on timescales of 20 ksec. A variable primary continuum dominates the high energy spectrum (>10 keV) in all the states, while the reflected/scattered flux which dominates at E< 10 keV stays approximately constant. From modelling the complex reflection/transmission spectrum we derive a Compton depth along the line of sight of tau_Thomson ~ 2.9, and a global covering factor for the circumnuclear gas of ~ 0.15. This agrees with the constraints derived from the high energy variability, which implies that most of the high energy flux is transmitted, rather that Compton-scattered. This demonstrates the effectiveness of spectral analysis in constraining the geometric properties of the circumnuclear gas, and validates similar methods used for analyzing the spectra of other bright, Compton-thick AGN. The lower limits on the e-folding energy are between 200-300 keV, consistent with previous BeppoSAX, Suzaku and Swift BAT observations. The accretion rate, estimated from the X-ray luminosity and assuming a bolometric correction typical of type 2 AGN, is in the range ~0.1-0.3 lambda_Edd depending on the flux state. The substantial observed X-ray luminosity variability of NGC4945 implies that large errors can arise from using single-epoch X-ray data to derive L/L_Edd values for obscured AGNs.Comment: Accepted for publication in Ap

Catching Element Formation In The Act

Gamma-ray astronomy explores the most energetic photons in nature to address some of the most pressing puzzles in contemporary astrophysics. It encompasses a wide range of objects and phenomena: stars, supernovae, novae, neutron stars, stellar-mass black holes, nucleosynthesis, the interstellar medium, cosmic rays and relativistic-particle acceleration, and the evolution of galaxies. MeV gamma-rays provide a unique probe of nuclear processes in astronomy, directly measuring radioactive decay, nuclear de-excitation, and positron annihilation. The substantial information carried by gamma-ray photons allows us to see deeper into these objects, the bulk of the power is often emitted at gamma-ray energies, and radioactivity provides a natural physical clock that adds unique information. New science will be driven by time-domain population studies at gamma-ray energies. This science is enabled by next-generation gamma-ray instruments with one to two orders of magnitude better sensitivity, larger sky coverage, and faster cadence than all previous gamma-ray instruments. This transformative capability permits: (a) the accurate identification of the gamma-ray emitting objects and correlations with observations taken at other wavelengths and with other messengers; (b) construction of new gamma-ray maps of the Milky Way and other nearby galaxies where extended regions are distinguished from point sources; and (c) considerable serendipitous science of scarce events -- nearby neutron star mergers, for example. Advances in technology push the performance of new gamma-ray instruments to address a wide set of astrophysical questions.Comment: 14 pages including 3 figure

Estrogen/progesterone Receptor and HER2 Discordance Between Primary Tumor and Brain Metastases in Breast Cancer and Its Effect on Treatment and Survival

BACKGROUND: Breast cancer treatment is based on estrogen receptors (ERs), progesterone receptors (PRs), and human epidermal growth factor receptor 2 (HER2). At the time of metastasis, receptor status can be discordant from that at initial diagnosis. The purpose of this study was to determine the incidence of discordance and its effect on survival and subsequent treatment in patients with breast cancer brain metastases (BCBM). METHODS: A retrospective database of 316 patients who underwent craniotomy for BCBM between 2006 and 2017 was created. Discordance was considered present if the ER, PR, or HER2 status differed between the primary tumor and the BCBM. RESULTS: The overall receptor discordance rate was 132/316 (42%), and the subtype discordance rate was 100/316 (32%). Hormone receptors (HR, either ER or PR) were gained in 40/160 (25%) patients with HR-negative primary tumors. HER2 was gained in 22/173 (13%) patients with HER2-negative primary tumors. Subsequent treatment was not adjusted for most patients who gained receptors-nonetheless, median survival (MS) improved but did not reach statistical significance (HR, 17-28 mo, P = 0.12; HER2, 15-19 mo, P = 0.39). MS for patients who lost receptors was worse (HR, 27-18 mo, P = 0.02; HER2, 30-18 mo, P = 0.08). CONCLUSIONS: Receptor discordance between primary tumor and BCBM is common, adversely affects survival if receptors are lost, and represents a missed opportunity for use of effective treatments if receptors are gained. Receptor analysis of BCBM is indicated when clinically appropriate. Treatment should be adjusted accordingly. KEY POINTS: 1. Receptor discordance alters subtype in 32% of BCBM patients.2. The frequency of receptor gain for HR and HER2 was 25% and 13%, respectively.3. If receptors are lost, survival suffers. If receptors are gained, consider targeted treatment