A coordinated phosphorylation cascade initiated by MSK1 directs RAR alpha recruitment to target gene promoters

The nuclear retinoic acid (RA) receptor alpha (RARα) is a transcriptional transregulator that controls the expression of specific gene subsets through binding at response elements and dynamic interactions with coregulators, which are coordinated by the ligand. Here, we highlighted a novel paradigm in which the transcription of RARα-target genes is controlled by phosphorylation cascades initiated by the rapid RA activation of the p38MAPK/MSK1 pathway. We demonstrate that MSK1 phosphorylates RARα at S369 located in the Ligand Binding Domain, allowing the binding of TFIIH and thereby phosphorylation of the N-terminal domain at S77 by cdk7/cyclin H. MSK1 also phosphorylates Histone H3 at S10. Finally, the phosphorylation cascade initiated by MSK1 is required for the recruitment of RARα/TFIIH complexes to response elements and subsequently for RARα target genes activation. Cancer cells characterized by a deregulated p38MAPK/MSK1 pathway, do not respond to RA, outlining the essential contribution of the RA-triggered phosphorylation cascade in RA signaling

UC-262 GTRI: IT Web Management Project

This project is meant to develop a baseline web application that will support development of future tools for managing an IT department (licensing, asset tracking, budget management, self-service software/configuration, issue management/tickets, etc.) As well as provide a free IT Management tool that an IT manager can easily access and use.  Having an IT management tool to aid with different things such as tracking, budget management and more is very essential to efficiently run an IT department. There are various tools to assist with that which exist today. However, as pointed out by our client GTRI, a lot of them are poorly designed. Hence, our project seeks to help solve this issue by developing a baseline web application that will support development of future tools for managing an IT department and provide functionalitie

How to produce a diagnostic opinion at a distance? New forms of tele-expertise use in France and their transformational effects on healthcare practices in dermatology

How to produce a diagnostic opinion at a distance, without seeing and examining patients? This is the challenge of tele-expertise (TLX), defined first in legal terms, as one of the five telemedicine acts in France. It consists of a particular form of healthcare practice in which a physician, known as the “requester”, solicits remotely the opinion of another practitioner, a specialist known as the “requested”, by sharing with him/her clinical information and photographs that he/she produces for this purpose, based on the medical examination of the patient. This practice is certainly not new; it is inherent to any medical activity where it develops outside of any legislative and regulatory framework, between practitioners who already know each other more or less well. So the novelty of the recent forms of TLX as a legally recognized medical act in its own right, relies mainly on the development of secure file exchange platforms within territorialized care networks, the systematization of these practices beyond the networks of acquaintances and their coverage by the health insurance. The purpose of this article is to describe the various usages of this new form of TLX, as well as to understand how they contribute to the in-depth transformation of care practices and organizations. It suggests doing so in the specific case of dermatology, through a qualitative study based on semi-directive interviews approximately with fifty French dermatologists, mainly requested experts, practicing TLX both in the context of private practice and in a hospital setting. The results of this empirical study are presented in three parts. First, we will consider the specificity of dermatological practice and describe the particular ways in which TLX is being implemented in this field, as a new framework. Then, we will report on the multiples efforts and skills needed to produce a diagnostic opinion remotely. We will lastly present various uses that dermatologists develop of TLX in different socio-organizational configurations. We will finally discuss how these uses transform the usual practices of dermatologists, not only by creating a new type of activity, but also by allowing them to participate differently in the organization of care pathways

Does the Debris Disk around HD 32297 Contain Cometary Grains?

We present an adaptive optics imaging detection of the HD 32297 debris disk at L' (3.8 \microns) obtained with the LBTI/LMIRcam infrared instrument at the LBT. The disk is detected at signal-to-noise per resolution element ~ 3-7.5 from ~ 0.3-1.1" (30-120 AU). The disk at L' is bowed, as was seen at shorter wavelengths. This likely indicates the disk is not perfectly edge-on and contains highly forward scattering grains. Interior to ~ 50 AU, the surface brightness at L' rises sharply on both sides of the disk, which was also previously seen at Ks band. This evidence together points to the disk containing a second inner component located at $\lesssim$ 50 AU. Comparing the color of the outer (50 $< r$/AU $< 120$) portion of the disk at L' with archival HST/NICMOS images of the disk at 1-2 \microns allows us to test the recently proposed cometary grains model of Donaldson et al. 2013. We find that the model fails to match the disk's surface brightness and spectrum simultaneously (reduced chi-square = 17.9). When we modify the density distribution of the model disk, we obtain a better overall fit (reduced chi-square = 2.9). The best fit to all of the data is a pure water ice model (reduced chi-square = 1.06), but additional resolved imaging at 3.1 \microns is necessary to constrain how much (if any) water ice exists in the disk, which can then help refine the originally proposed cometary grains model.Comment: Accepted to ApJ January 13, 2014. 12 pages (emulateapj style), 9 figures, 1 tabl

Placental Passage of Protopine in an Ex Vivo Human Perfusion System

The placental passage of protopine was investigated with a human ex vivo placental perfusion model. The model was first validated with diazepam and citalopram, 2 compounds known to cross the placental barrier, and antipyrine as a positive control. All compounds were quantified by partially validated U(H)PLC-MS/MS bioanalytical methods. Protopine was transferred from the maternal to the fetal circuit, with a steady-state reached after 90 min. The study compound did not affect placental viability or functionality, as glucose consumption, lactate production, and beta-human chorionic gonadotropin, and leptin release remained constant. Histopathological evaluation of all placental specimens showed unremarkable, age-appropriate parenchymal maturation with no pathologic findings

High contrast imaging at the LBT: the LEECH exoplanet imaging survey

In Spring 2013, the LEECH (LBTI Exozodi Exoplanet Common Hunt) survey began its $\sim$130-night campaign from the Large Binocular Telescope (LBT) atop Mt Graham, Arizona. This survey benefits from the many technological achievements of the LBT, including two 8.4-meter mirrors on a single fixed mount, dual adaptive secondary mirrors for high Strehl performance, and a cold beam combiner to dramatically reduce the telescope's overall background emissivity. LEECH neatly complements other high-contrast planet imaging efforts by observing stars at L' (3.8 $\mu$m), as opposed to the shorter wavelength near-infrared bands (1-2.4 $\mu$m) of other surveys. This portion of the spectrum offers deep mass sensitivity, especially around nearby adolescent ($\sim$0.1-1 Gyr) stars. LEECH's contrast is competitive with other extreme adaptive optics systems, while providing an alternative survey strategy. Additionally, LEECH is characterizing known exoplanetary systems with observations from 3-5$\mu$m in preparation for JWST.Comment: 12 pages, 5 figures. Proceedings of the SPIE, 9148-2

Constraints on the architecture of the HD 95086 planetary system with the Gemini Planet Imager

We present astrometric monitoring of the young exoplanet HD 95086 b obtained with the Gemini Planet Imager between 2013 and 2016. A small but significant position angle change is detected at constant separation; the orbital motion is confirmed with literature measurements. Efficient Monte Carlo techniques place preliminary constraints on the orbital parameters of HD 95086 b. With 68% confidence, a semimajor axis of 61.7^{+20.7}_{-8.4} au and an inclination of 153.0^{+9.7}_{-13.5} deg are favored, with eccentricity less than 0.21. Under the assumption of a co-planar planet-disk system, the periastron of HD 95086 b is beyond 51 au with 68% confidence. Therefore HD 95086 b cannot carve the entire gap inferred from the measured infrared excess in the SED of HD 95086. We use our sensitivity to additional planets to discuss specific scenarios presented in the literature to explain the geometry of the debris belts. We suggest that either two planets on moderately eccentric orbits or three to four planets with inhomogeneous masses and orbital properties are possible. The sensitivity to additional planetary companions within the observations presented in this study can be used to help further constrain future dynamical simulations of the planet-disk system.Comment: Accepted for publication in ApJ

The LEECH Exoplanet Imaging Survey: Limits on Planet Occurrence Rates Under Conservative Assumptions

We present the results of the largest $L^{\prime}$ ($3.8~\mu$m) direct imaging survey for exoplanets to date, the Large Binocular Telescope Interferometer (LBTI) Exozodi Exoplanet Common Hunt (LEECH). We observed 98 stars with spectral types from B to M. Cool planets emit a larger share of their flux in $L^{\prime}$ compared to shorter wavelengths, affording LEECH an advantage in detecting low-mass, old, and cold-start giant planets. We emphasize proximity over youth in our target selection, probing physical separations smaller than other direct imaging surveys. For FGK stars, LEECH outperforms many previous studies, placing tighter constraints on the hot-start planet occurrence frequency interior to $\sim20$ au. For less luminous, cold-start planets, LEECH provides the best constraints on giant-planet frequency interior to $\sim20$ au around FGK stars. Direct imaging survey results depend sensitively on both the choice of evolutionary model (e.g., hot- or cold-start) and assumptions (explicit or implicit) about the shape of the underlying planet distribution, in particular its radial extent. Artificially low limits on the planet occurrence frequency can be derived when the shape of the planet distribution is assumed to extend to very large separations, well beyond typical protoplanetary dust-disk radii ($\lesssim50$ au), and when hot-start models are used exclusively. We place a conservative upper limit on the planet occurrence frequency using cold-start models and planetary population distributions that do not extend beyond typical protoplanetary dust-disk radii. We find that $\lesssim90\%$ of FGK systems can host a 7 to 10 $M_{\mathrm{Jup}}$ planet from 5 to 50 au. This limit leaves open the possibility that planets in this range are common.Comment: 31 pages, 13 figures, accepted to A

Automated data processing architecture for the Gemini Planet Imager Exoplanet Survey

The Gemini Planet Imager Exoplanet Survey (GPIES) is a multi-year direct imaging survey of 600 stars to discover and characterize young Jovian exoplanets and their environments. We have developed an automated data architecture to process and index all data related to the survey uniformly. An automated and flexible data processing framework, which we term the Data Cruncher, combines multiple data reduction pipelines together to process all spectroscopic, polarimetric, and calibration data taken with GPIES. With no human intervention, fully reduced and calibrated data products are available less than an hour after the data are taken to expedite follow-up on potential objects of interest. The Data Cruncher can run on a supercomputer to reprocess all GPIES data in a single day as improvements are made to our data reduction pipelines. A backend MySQL database indexes all files, which are synced to the cloud, and a front-end web server allows for easy browsing of all files associated with GPIES. To help observers, quicklook displays show reduced data as they are processed in real-time, and chatbots on Slack post observing information as well as reduced data products. Together, the GPIES automated data processing architecture reduces our workload, provides real-time data reduction, optimizes our observing strategy, and maintains a homogeneously reduced dataset to study planet occurrence and instrument performance.Comment: 21 pages, 3 figures, accepted in JATI

Dynamical Mass Measurement of the Young Spectroscopic Binary V343 Normae AaAb Resolved With the Gemini Planet Imager

We present new spatially resolved astrometry and photometry from the Gemini Planet Imager of the inner binary of the young multiple star system V343 Normae, which is a member of the beta Pictoris moving group. V343 Normae comprises a K0 and mid-M star in a ~4.5 year orbit (AaAb) and a wide 10" M5 companion (B). By combining these data with archival astrometry and radial velocities we fit the orbit and measure individual masses for both components of M_Aa = 1.10 +/- 0.10 M_sun and M_Ab = 0.290 +/- 0.018 M_sun. Comparing to theoretical isochrones, we find good agreement for the measured masses and JHK band magnitudes of the two components consistent with the age of the beta Pic moving group. We derive a model-dependent age for the beta Pic moving group of 26 +/- 3 Myr by combining our results for V343 Normae with literature measurements for GJ 3305, which is another group member with resolved binary components and dynamical masses.Comment: 12 pages, 7 figures. Accepted to A