Identification of plant-derived alkaloids with therapeutic potential for myotonic dystrophy type I

Myotonic dystrophy type I (DM1) is a disabling neuromuscular disease with no causal treatment available. This disease is caused by expanded CTG trinucleotide repeats in the 3 UTR of the dystrophia myotonica protein kinase gene. On the RNA level, expanded (CUG)n repeats form hairpin structures that sequester splicing factors such as muscleblind-like 1 (MBNL1). Lack of availableMBNL1leads to misregulated alternative splicing of many target pre-mRNAs, leading to the multisystemic symptoms in DM1. Many studies aiming to identify small molecules that target the (CUG)n-MBNL1 complex focused on synthetic molecules. In an effort to identify new small molecules that liberate sequesteredMBNL1from (CUG)n RNA, we focused specifically on small molecules of natural origin. Natural products remain an important source for drugs and play a significant role in providing novel leads and pharmacophores for medicinal chemistry. In a new DM1 mechanism-based biochemical assay, we screened a collection of isolated natural compounds and a library of over 2100 extracts from plants and fungal strains. HPLC-based activity profiling in combination with spectroscopic methods were used to identify the active principles in the extracts. The bioactivity of the identified compounds was investigated in a human cell model and in a mouse model of DM1.We identified several alkaloids, including the -carboline harmine and the isoquinoline berberine, that ameliorated certain aspects of theDM1pathology in these models. Alkaloids as a compound class may have potential for drug discovery in other RNA-mediated diseases

The effect of pair-instability mass loss on black-hole mergers

Context. Mergers of two stellar-origin black holes are a prime source of gravitational waves and are under intensive investigation. One crucial ingredient in their modeling has been neglected: pair-instability pulsation supernovae with associated severe mass loss may suppress the formation of massive black holes, decreasing black-hole-merger rates for the highest black-hole masses. Aims. We demonstrate the effects of pair-instability pulsation supernovae on merger rate and mass using populations of double black-hole binaries formed through the isolated binary classical evolution channel. Methods. The mass loss from pair-instability pulsation supernova is estimated based on existing hydrodynamical calculations. This mass loss is incorporated into the StarTrack population synthesis code. StarTrack is used to generate double black-hole populations with and without pair-instability pulsation supernova mass loss. Results. The mass loss associated with pair-instability pulsation supernovae limits the Population I/II stellar-origin black-hole mass to 50 M⊙, in tension with earlier predictions that the maximum black-hole mass could be as high as 100 M⊙. In our model, neutron stars form with mass 1−2 M⊙. We then encounter the first mass gap at 2−5 M⊙ with the compact object absence due to rapid supernova explosions, followed by the formation of black holes with mass 5−50 M⊙, with a second mass gap at 50−135 M⊙ created by pair-instability pulsation supernovae and by pair-instability supernovae. Finally, black holes with masses above 135 M⊙ may potentially form to arbitrarily high mass limited only by the extent of the initial mass function and the strength of stellar winds. Suppression of double black-hole-merger rates by pair-instability pulsation supernovae is negligible for our evolutionary channel. Our standard evolutionary model, with the inclusion of pair-instability pulsation supernovae and pair-instability supernovae, is fully consistent with the Laser Interferometric Gravitational-wave Observatory (LIGO) observations of black-hole mergers: GW150914, GW151226, and LVT151012. The LIGO results are inconsistent with high (≳ 400 km s-1) black hole (BH) natal kicks. We predict the detection of several, and up to as many as ~60, BH-BH mergers with a total mass of 10−150 M⊙ (most likely range: 20−80 M⊙) in the forthcoming ~60 effective days of the LIGO O2 observations, assuming the detectors reach the optimistic target O2 sensitivity

Point Source Polarimetry with the Gemini Planet Imager: Sensitivity Characterization with T5.5 Dwarf Companion HD 19467 B

Detecting polarized light from self-luminous exoplanets has the potential to provide key information about rotation, surface gravity, cloud grain size, and cloud coverage. While field brown dwarfs with detected polarized emission are common, no exoplanet or substellar companion has yet been detected in polarized light. With the advent of high contrast imaging spectro-polarimeters such as GPI and SPHERE, such a detection may now be possible with careful treatment of instrumental polarization. In this paper, we present 28 minutes of H-band GPI polarimetric observations of the benchmark T5.5 companion HD 19467 B. We detect no polarization signal from the target, and place an upper limit on the degree of linear polarization of p_(CL99.73%) ⩽ 2.4%. We discuss our results in the context of T dwarf cloud models and photometric variability

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

Improving and Assessing Planet Sensitivity of the GPI Exoplanet Survey with a Forward Model Matched Filter

We present a new matched filter algorithm for direct detection of point sources in the immediate vicinity of bright stars. The stellar Point Spread Function (PSF) is first subtracted using a Karhunen-Lo\'eve Image Processing (KLIP) algorithm with Angular and Spectral Differential Imaging (ADI and SDI). The KLIP-induced distortion of the astrophysical signal is included in the matched filter template by computing a forward model of the PSF at every position in the image. To optimize the performance of the algorithm, we conduct extensive planet injection and recovery tests and tune the exoplanet spectra template and KLIP reduction aggressiveness to maximize the Signal-to-Noise Ratio (SNR) of the recovered planets. We show that only two spectral templates are necessary to recover any young Jovian exoplanets with minimal SNR loss. We also developed a complete pipeline for the automated detection of point source candidates, the calculation of Receiver Operating Characteristics (ROC), false positives based contrast curves, and completeness contours. We process in a uniform manner more than 330 datasets from the Gemini Planet Imager Exoplanet Survey (GPIES) and assess GPI typical sensitivity as a function of the star and the hypothetical companion spectral type. This work allows for the first time a comparison of different detection algorithms at a survey scale accounting for both planet completeness and false positive rate. We show that the new forward model matched filter allows the detection of $50\%$ fainter objects than a conventional cross-correlation technique with a Gaussian PSF template for the same false positive rate.Comment: ApJ accepte

GPI spectra of HR 8799 c, d, and e from 1.5 to 2.4μ\mum with KLIP Forward Modeling

We explore KLIP forward modeling spectral extraction on Gemini Planet Imager coronagraphic data of HR 8799, using PyKLIP and show algorithm stability with varying KLIP parameters. We report new and re-reduced spectrophotometry of HR 8799 c, d, and e in H & K bands. We discuss a strategy for choosing optimal KLIP PSF subtraction parameters by injecting simulated sources and recovering them over a range of parameters. The K1/K2 spectra for HR 8799 c and d are similar to previously published results from the same dataset. We also present a K band spectrum of HR 8799 e for the first time and show that our H-band spectra agree well with previously published spectra from the VLT/SPHERE instrument. We show that HR 8799 c and d show significant differences in their H & K spectra, but do not find any conclusive differences between d and e or c and e, likely due to large error bars in the recovered spectrum of e. Compared to M, L, and T-type field brown dwarfs, all three planets are most consistent with mid and late L spectral types. All objects are consistent with low gravity but a lack of standard spectra for low gravity limit the ability to fit the best spectral type. We discuss how dedicated modeling efforts can better fit HR 8799 planets' near-IR flux and discuss how differences between the properties of these planets can be further explored.Comment: Accepted to AJ, 25 pages, 16 Figure

Performance of the Gemini Planet Imager Non-Redundant Mask and spectroscopy of two close-separation binaries HR 2690 and HD 142527

The Gemini Planet Imager (GPI) contains a 10-hole non-redundant mask (NRM), enabling interferometric resolution in complement to its coronagraphic capabilities. The NRM operates both in spectroscopic (integral field spectrograph, henceforth IFS) and polarimetric configurations. NRM observations were taken between 2013 and 2016 to characterize its performance. Most observations were taken in spectroscopic mode with the goal of obtaining precise astrometry and spectroscopy of faint companions to bright stars. We find a clear correlation between residual wavefront error measured by the AO system and the contrast sensitivity by comparing phase errors in observations of the same source, taken on different dates. We find a typical 5-$\sigma$ contrast sensitivity of $2-3~\times~10^{-3}$ at $\sim\lambda/D$. We explore the accuracy of spectral extraction of secondary components of binary systems by recovering the signal from a simulated source injected into several datasets. We outline data reduction procedures unique to GPI's IFS and describe a newly public data pipeline used for the presented analyses. We demonstrate recovery of astrometry and spectroscopy of two known companions to HR 2690 and HD 142527. NRM+polarimetry observations achieve differential visibility precision of $\sigma\sim0.4\%$ in the best case. We discuss its limitations on Gemini-S/GPI for resolving inner regions of protoplanetary disks and prospects for future upgrades. We summarize lessons learned in observing with NRM in spectroscopic and polarimetric modes.Comment: Accepted to AJ, 22 pages, 14 figure

Characterizing 51 Eri b from 1-5 μ\mum: a partly-cloudy exoplanet

We present spectro-photometry spanning 1-5 $\mu$m of 51 Eridani b, a 2-10 M$_\text{Jup}$ planet discovered by the Gemini Planet Imager Exoplanet Survey. In this study, we present new $K1$ (1.90-2.19 $\mu$m) and $K2$ (2.10-2.40 $\mu$m) spectra taken with the Gemini Planet Imager as well as an updated $L_P$ (3.76 $\mu$m) and new $M_S$ (4.67 $\mu$m) photometry from the NIRC2 Narrow camera. The new data were combined with $J$ (1.13-1.35 $\mu$m) and $H$ (1.50-1.80 $\mu$m) spectra from the discovery epoch with the goal of better characterizing the planet properties. 51 Eri b photometry is redder than field brown dwarfs as well as known young T-dwarfs with similar spectral type (between T4-T8) and we propose that 51 Eri b might be in the process of undergoing the transition from L-type to T-type. We used two complementary atmosphere model grids including either deep iron/silicate clouds or sulfide/salt clouds in the photosphere, spanning a range of cloud properties, including fully cloudy, cloud free and patchy/intermediate opacity clouds. Model fits suggest that 51 Eri b has an effective temperature ranging between 605-737 K, a solar metallicity, a surface gravity of $\log$(g) = 3.5-4.0 dex, and the atmosphere requires a patchy cloud atmosphere to model the SED. From the model atmospheres, we infer a luminosity for the planet of -5.83 to -5.93 ($\log L/L_{\odot}$), leaving 51 Eri b in the unique position as being one of the only directly imaged planet consistent with having formed via cold-start scenario. Comparisons of the planet SED against warm-start models indicates that the planet luminosity is best reproduced by a planet formed via core accretion with a core mass between 15 and 127 M$_{\oplus}$.Comment: 27 pages, 19 figures, Accepted for publication in The Astronomical Journa