The Post-Pericenter Evolution of the Galactic Center Source G2

In early 2014 the fast-moving near-infrared source G2 reached its closest approach to the supermassive black hole Sgr A* in the Galactic Center. We report on the evolution of the ionized gaseous component and the dusty component of G2 immediately after this event, revealed by new observations obtained in 2015 and 2016 with the SINFONI integral field spectrograph and the NACO imager at the ESO VLT. The spatially resolved dynamics of the Br$\gamma$ line emission can be accounted for by the ballistic motion and tidal shearing of a test-particle cloud that has followed a highly eccentric Keplerian orbit around the black hole for the last 12 years. The non-detection of a drag force or any strong hydrodynamic interaction with the hot gas in the inner accretion zone limits the ambient density to less than a few 10$^3$ cm$^{-3}$ at the distance of closest approach (1500 $R_s$), assuming G2 is a spherical cloud moving through a stationary and homogeneous atmosphere. The dust continuum emission is unresolved in L'-band, but stays consistent with the location of the Br$\gamma$ emission. The total luminosity of the Br$\gamma$ and L' emission has remained constant to within the measurement uncertainty. The nature and origin of G2 are likely related to that of the precursor source G1, since their orbital evolution is similar, though not identical. Both object are also likely related to a trailing tail structure, which is continuously connected to G2 over a large range in position and radial velocity.Comment: 17 pages, 12 figures; accepted for publication in Ap

Optical Distortion in the NACO Imager

In this research note, we present a set of distortion solutions that may be used to correct geometric optical distortion in images taken with the S13 camera of the NACO adaptive optics imager.Comment: published in the RNAA

Overexpression of Inosine 5′-Monophosphate Dehydrogenase Type II Mediates Chemoresistance to Human Osteosarcoma Cells

overexpression in osteosarcoma patients with poor response to chemotherapy. The aim of this study was to provide evidence for direct involvement of IMPDH2 in the development of chemoresistance..IMPDH2 is directly involved in the development of chemoresistance in osteosarcoma cells, suggesting that targeting of IMPDH2 by RNAi or more effective pharmacological inhibitors in combination with chemotherapy might be a promising means of overcoming chemoresistance in osteosarcomas with high IMPDH2 expression

Sgr A* near-infrared flares from reconnection events in a magnetically arrested disc

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.Comment: revised version, MNRAS, in pres

A Regression-based K nearest neighbor algorithm for gene function prediction from heterogeneous data

BACKGROUND: As a variety of functional genomic and proteomic techniques become available, there is an increasing need for functional analysis methodologies that integrate heterogeneous data sources. METHODS: In this paper, we address this issue by proposing a general framework for gene function prediction based on the k-nearest-neighbor (KNN) algorithm. The choice of KNN is motivated by its simplicity, flexibility to incorporate different data types and adaptability to irregular feature spaces. A weakness of traditional KNN methods, especially when handling heterogeneous data, is that performance is subject to the often ad hoc choice of similarity metric. To address this weakness, we apply regression methods to infer a similarity metric as a weighted combination of a set of base similarity measures, which helps to locate the neighbors that are most likely to be in the same class as the target gene. We also suggest a novel voting scheme to generate confidence scores that estimate the accuracy of predictions. The method gracefully extends to multi-way classification problems. RESULTS: We apply this technique to gene function prediction according to three well-known Escherichia coli classification schemes suggested by biologists, using information derived from microarray and genome sequencing data. We demonstrate that our algorithm dramatically outperforms the naive KNN methods and is competitive with support vector machine (SVM) algorithms for integrating heterogenous data. We also show that by combining different data sources, prediction accuracy can improve significantly. CONCLUSION: Our extension of KNN with automatic feature weighting, multi-class prediction, and probabilistic inference, enhance prediction accuracy significantly while remaining efficient, intuitive and flexible. This general framework can also be applied to similar classification problems involving heterogeneous datasets

Phenotype of autosomal dominant spastic paraplegia linked to chromosome 2

Summary We report the clinical features of 12 families with autosomal dominant spastic paraplegia (ADSP) linked to the SPG4 locus on chromosome 2p, the major locus for this disorder that accounts for ∼40% of the families. Among 93 gene carriers, 32 (34%) were unaware of symptoms but were clinically affected. Haplotype reconstruction showed that 90% of the asymptomatic gene carriers presented increased reflexes and/or extensor plantar responses independent of age at examination. The mean age at onset was 29 years, ranging from 1 to 63 years. Intra- as well as inter-familial variability of age at onset was important, but did not result from anticipation. Phenotype—genotype correlations and comparison with SPG3 and SPG5 families indicated that despite the variability of age at onset, SPG4 is a single genetic entity but no clinical features distinguish individual SPG4 patients from those with SPG3 or SPG5 mutation

First direct detection of an exoplanet by optical interferometry; Astrometry and K-band spectroscopy of HR8799 e

To date, infrared interferometry at best achieved contrast ratios of a few times $10^{-4}$ on bright targets. GRAVITY, with its dual-field mode, is now capable of high contrast observations, enabling the direct observation of exoplanets. We demonstrate the technique on HR8799, a young planetary system composed of four known giant exoplanets. We used the GRAVITY fringe tracker to lock the fringes on the central star, and integrated off-axis on the HR8799e planet situated at 390 mas from the star. Data reduction included post-processing to remove the flux leaking from the central star and to extract the coherent flux of the planet. The inferred K band spectrum of the planet has a spectral resolution of 500. We also derive the astrometric position of the planet relative to the star with a precision on the order of 100$\,\mu$as. The GRAVITY astrometric measurement disfavors perfectly coplanar stable orbital solutions. A small adjustment of a few degrees to the orbital inclination of HR 8799 e can resolve the tension, implying that the orbits are close to, but not strictly coplanar. The spectrum, with a signal-to-noise ratio of $\approx 5$ per spectral channel, is compatible with a late-type L brown dwarf. Using Exo-REM synthetic spectra, we derive a temperature of $1150\pm50$\,K and a surface gravity of $10^{4.3\pm0.3}\,$cm/s$^{2}$. This corresponds to a radius of $1.17^{+0.13}_{-0.11}\,R_{\rm Jup}$ and a mass of $10^{+7}_{-4}\,M_{\rm Jup}$, which is an independent confirmation of mass estimates from evolutionary models. Our results demonstrate the power of interferometry for the direct detection and spectroscopic study of exoplanets at close angular separations from their stars.Comment: published in A&

Multiwavelength Variability of Sagittarius A* in 2019 July

We report timing analysis of near-infrared (NIR), X-ray, and sub-millimeter (submm) data during a three-day coordinated campaign observing Sagittarius A*. Data were collected at 4.5 micron with the Spitzer Space Telescope, 2-8 keV with the Chandra X-ray Observatory, 3-70 keV with NuSTAR, 340 GHz with ALMA, and at 2.2 micron with the GRAVITY instrument on the Very Large Telescope Interferometer. Two dates show moderate variability with no significant lags between the submm and the infrared at 99% confidence. July 18 captured a moderately bright NIR flare (F_K ~ 15 mJy) simultaneous with an X-ray flare (F ~ 0.1 cts/s) that most likely preceded bright submm flux (F ~ 5.5 Jy) by about +34 (+14 -33) minutes at 99% confidence. The uncertainty in this lag is dominated by the fact that we did not observe the peak of the submm emission. A synchrotron source cooled through adiabatic expansion can describe a rise in the submm once the synchrotron-self-Compton NIR and X-ray peaks have faded. This model predicts high GHz and THz fluxes at the time of the NIR/X-ray peak and electron densities well above those implied from average accretion rates for Sgr A*. However, the higher electron density postulated in this scenario would be in agreement with the idea that 2019 was an extraordinary epoch with a heightened accretion rate. Since the NIR and X-ray peaks can also be fit by a non-thermal synchrotron source with lower electron densities, we cannot rule out an unrelated chance coincidence of this bright submm flare with the NIR/X-ray emission.Comment: Accepted for publication in The Astrophysical Journa

Replication and Virus-Induced Transcriptome of HAdV-5 in Normal Host Cells versus Cancer Cells - Differences of Relevance for Adenoviral Oncolysis

Adenoviruses (Ads), especially HAdV-5, have been genetically equipped with tumor-restricted replication potential to enable applications in oncolytic cancer therapy. Such oncolytic adenoviruses have been well tolerated in cancer patients, but their anti-tumor efficacy needs to be enhanced. In this regard, it should be considered that cancer cells, dependent on their tissue of origin, can differ substantially from the normal host cells to which Ads are adapted by complex virus-host interactions. Consequently, viral replication efficiency, a key determinant of oncolytic activity, might be suboptimal in cancer cells. Therefore, we have analyzed both the replication kinetics of HAdV-5 and the virus-induced transcriptome in human bronchial epithelial cells (HBEC) in comparison to cancer cells. This is the first report on genome-wide expression profiling of Ads in their native host cells. We found that E1A expression and onset of viral genome replication are most rapid in HBEC and considerably delayed in melanoma cells. In squamous cell lung carcinoma cells, we observed intermediate HAdV-5 replication kinetics. Infectious particle production, viral spread and lytic activity of HAdV-5 were attenuated in melanoma cells versus HBEC. Expression profiling at the onset of viral genome replication revealed that HAdV-5 induced the strongest changes in the cellular transcriptome in HBEC, followed by lung cancer and melanoma cells. We identified prominent regulation of genes involved in cell cycle and DNA metabolism, replication and packaging in HBEC, which is in accord with the necessity to induce S phase for viral replication. Strikingly, in melanoma cells HAdV-5 triggered opposing regulation of said genes and, in contrast to lung cancer cells, no weak S phase induction was detected when using the E2F promoter as reporter. Our results provide a rationale for improving oncolytic adenoviruses either by adaptation of viral infection to target tumor cells or by modulating tumor cell functions to better support viral replication