No Conclusive Evidence for Transits of Proxima b in MOST photometry

The analysis of Proxima Centauri's radial velocities recently led Anglada-Escud\'e et al. (2016) to claim the presence of a low mass planet orbiting the Sun's nearest star once every 11.2 days. Although the a-priori probability that Proxima b transits its parent star is just 1.5%, the potential impact of such a discovery would be considerable. Independent of recent radial velocity efforts, we observed Proxima Centauri for 12.5 days in 2014 and 31 days in 2015 with the MOST space telescope. We report here that we cannot make a compelling case that Proxima b transits in our precise photometric time series. Imposing an informative prior on the period and phase, we do detect a candidate signal with the expected depth. However, perturbing the phase prior across 100 evenly spaced intervals reveals one strong false-positive and one weaker instance. We estimate a false-positive rate of at least a few percent and a much higher false-negative rate of 20-40%, likely caused by the very high flare rate of Proxima Centauri. Comparing our candidate signal to HATSouth ground-based photometry reveals that the signal is somewhat, but not conclusively, disfavored (1-2 sigmas) leading us to argue that the signal is most likely spurious. We expect that infrared photometric follow-up could more conclusively test the existence of this candidate signal, owing to the suppression of flare activity and the impressive infrared brightness of the parent star.Comment: Accepted to ApJ. Posterior samples, MOST photometry and HATSouth photometry are all available at https://github.com/CoolWorlds/Proxim

Spectroscopy, MOST Photometry, and Interferometry of MWC 314: Is it an LBV or an interacting binary?

MWC 314 is a bright candidate luminous blue variable that resides in a fairly close binary system, with an orbital period of 60.753$\pm$0.003 d. We observed MWC 314 with a combination of optical spectroscopy, broad-band ground- and space-based photometry, as well as with long baseline, near-infrared interferometry. We have revised the single-lined spectroscopic orbit and explored the photometric variability. The orbital light curve displays two minima each orbit that can be partially explained in terms of the tidal distortion of the primary that occurs around the time of periastron. The emission lines in the system are often double-peaked and stationary in their kinematics, indicative of a circumbinary disc. We find that the stellar wind or circumbinary disc is partially resolved in the K\prime-band with the longest baselines of the CHARA Array. From this analysis, we provide a simple, qualitative model in an attempt to explain the observations. From the assumption of Roche Lobe overflow and tidal synchronisation at periastron, we estimate the component masses to be M1 $\approx 5$ M$_\odot$ and M2$\approx 15$ M$_\odot$, which indicates a mass of the LBV that is extremely low. In addition to the orbital modulation, we discovered two pulsational modes with the MOST satellite. These modes are easily supported by a low-mass hydrogen-poor star, but cannot be easily supported by a star with the parameters of an LBV. The combination of these results provides evidence that the primary star was likely never a normal LBV, but rather is the product of binary interactions. As such, this system presents opportunities for studying mass-transfer and binary evolution with many observational techniques.Comment: 26 pages, 7 figures, 5 tables, 2 appendices with 7 additional tables and 2 additional figures. Accepted for publication in MNRA

Updated Planetary Mass Constraints of the Young V1298 Tau System Using MAROON-X

The early K-type T-Tauri star, V1298 Tau ($V=10\,{\rm mag}$, ${\rm age}\approx20-30\,{\rm Myr}$) hosts four transiting planets with radii ranging from $4.9-9.6\,R_\oplus$. The three inner planets have orbital periods of $\approx8-24\,{\rm d}$ while the outer planet's period is poorly constrained by single transits observed with \emph{K2} and \emph{TESS}. Planets b, c, and d are proto-sub-Neptunes that may be undergoing significant mass loss. Depending on the stellar activity and planet masses, they are expected to evolve into super-Earths/sub-Neptunes that bound the radius valley. Here we present results of a joint transit and radial velocity (RV) modelling analysis, which includes recently obtained \emph{TESS} photometry and MAROON-X RV measurements. Assuming circular orbits, we obtain a low-significance ($\approx2\sigma$) RV detection of planet c implying a mass of $19.8_{-8.9}^{+9.3}\,M_\oplus$ and a conservative $2\sigma$ upper limit of $<39\,M_\oplus$. For planets b and d, we derive $2\sigma$ upper limits of $M_{\rm b}<159\,M_\oplus$ and $M_{\rm d}<41\,M_\oplus$. For planet e, plausible discrete periods of $P_{\rm e}>55.4\,{\rm d}$ are ruled out at a $3\sigma$ level while seven solutions with $43.3<P_{\rm e}/{\rm d}<55.4$ are consistent with the most probable $46.768131\pm000076\,{\rm d}$ solution within $3\sigma$. Adopting the most probable solution yields a $2.6\sigma$ RV detection with mass a of $0.66\pm0.26\,M_{\rm Jup}$. Comparing the updated mass and radius constraints with planetary evolution and interior structure models shows that planets b, d, and e are consistent with predictions for young gas-rich planets and that planet c is consistent with having a water-rich core with a substantial ($\sim5\%$ by mass) H$_2$ envelope.Comment: 18 pages, 13 figures, accepted for publication in A

Uncovering spatiotemporal patterns of atrophy in progressive supranuclear palsy using unsupervised machine learning

To better understand the pathological and phenotypic heterogeneity of progressive supranuclear palsy and the links between the two, we applied a novel unsupervised machine learning algorithm (Subtype and Stage Inference) to the largest MRI data set to date of people with clinically diagnosed progressive supranuclear palsy (including progressive supranuclear palsy-Richardson and variant progressive supranuclear palsy syndromes). Our cohort is comprised of 426 progressive supranuclear palsy cases, of which 367 had at least one follow-up scan, and 290 controls. Of the progressive supranuclear palsy cases, 357 were clinically diagnosed with progressive supranuclear palsy-Richardson, 52 with a progressive supranuclear palsy-cortical variant (progressive supranuclear palsy-frontal, progressive supranuclear palsy-speech/language, or progressive supranuclear palsy-corticobasal), and 17 with a progressive supranuclear palsy-subcortical variant (progressive supranuclear palsy-parkinsonism or progressive supranuclear palsy-progressive gait freezing). Subtype and Stage Inference was applied to volumetric MRI features extracted from baseline structural (T1-weighted) MRI scans and then used to subtype and stage follow-up scans. The subtypes and stages at follow-up were used to validate the longitudinal consistency of subtype and stage assignments. We further compared the clinical phenotypes of each subtype to gain insight into the relationship between progressive supranuclear palsy pathology, atrophy patterns, and clinical presentation. The data supported two subtypes, each with a distinct progression of atrophy: a 'subcortical' subtype, in which early atrophy was most prominent in the brainstem, ventral diencephalon, superior cerebellar peduncles, and the dentate nucleus, and a 'cortical' subtype, in which there was early atrophy in the frontal lobes and the insula alongside brainstem atrophy. There was a strong association between clinical diagnosis and the Subtype and Stage Inference subtype with 82% of progressive supranuclear palsy-subcortical cases and 81% of progressive supranuclear palsy-Richardson cases assigned to the subcortical subtype and 82% of progressive supranuclear palsy-cortical cases assigned to the cortical subtype. The increasing stage was associated with worsening clinical scores, whilst the 'subcortical' subtype was associated with worse clinical severity scores compared to the 'cortical subtype' (progressive supranuclear palsy rating scale and Unified Parkinson's Disease Rating Scale). Validation experiments showed that subtype assignment was longitudinally stable (95% of scans were assigned to the same subtype at follow-up) and individual staging was longitudinally consistent with 90% remaining at the same stage or progressing to a later stage at follow-up. In summary, we applied Subtype and Stage Inference to structural MRI data and empirically identified two distinct subtypes of spatiotemporal atrophy in progressive supranuclear palsy. These image-based subtypes were differentially enriched for progressive supranuclear palsy clinical syndromes and showed different clinical characteristics. Being able to accurately subtype and stage progressive supranuclear palsy patients at baseline has important implications for screening patients on entry to clinical trials, as well as tracking disease progression

Amphipathic helices target perilipins 1-3 to lipid droplets

Perilipins (PLINs) play a key role in energy storage by orchestrating the activity of lipases on the surface of lipid droplets. Failure of this activity results in severe metabolic disease in humans. Unlike all other lipid droplet-associated proteins, PLINs localize almost exclusively to the phospholipid monolayer surrounding the droplet. To understand how they sense and associate with the unique topology of the droplet surface, we studied the localization of human PLINs inSaccharomyces cerevisiae,demonstrating that the targeting mechanism is highly conserved and that 11-mer repeat regions are sufficient for droplet targeting. Mutations designed to disrupt folding of this region into amphipathic helices (AHs) significantly decreased lipid droplet targetingin vivoandin vitro Finally, we demonstrated a substantial increase in the helicity of this region in the presence of detergent micelles, which was prevented by an AH-disrupting missense mutation. We conclude that highly conserved 11-mer repeat regions of PLINs target lipid droplets by folding into AHs on the droplet surface, thus enabling PLINs to regulate the interface between the hydrophobic lipid core and its surrounding hydrophilic environment.This work was supported by grants from The Wellcome Trust (091551 and 107064 to DBS), the U.K. NIHR Cambridge Biomedical Research Centre, the Medical Research Council (G0701446 to SS and a Doctoral training grant awarded to the University of Cambridge for ERR), core facilities at the MRC Metabolic Diseases Unit (MC_UU_12012/5) and by the Innovative Medicines Initiative Joint Undertaking, EMIF-Metabolism award.This is the final version of the article. It first appeared from ASBMB via https://doi.org/10.1074/jbc.M115.69104

Stratifying the Presymptomatic Phase of Genetic Frontotemporal Dementia by Serum NfL and pNfH: A Longitudinal Multicentre Study

Objective: Although the presymptomatic stages of frontotemporal dementia (FTD) provide a unique chance to delay or even prevent neurodegeneration by early intervention, they remain poorly defined. Leveraging a large multicenter cohort of genetic FTD mutation carriers, we provide a biomarker-based stratification and biomarker cascade of the likely most treatment-relevant stage within the presymptomatic phase: the conversion stage. Methods: We longitudinally assessed serum levels of neurofilament light (NfL) and phosphorylated neurofilament heavy (pNfH) in the Genetic FTD Initiative (GENFI) cohort (n = 444), using single-molecule array technique. Subjects comprised 91 symptomatic and 179 presymptomatic subjects with mutations in the FTD genes C9orf72, GRN, or MAPT, and 174 mutation-negative within-family controls. Results: In a biomarker cascade, NfL increase preceded the hypothetical clinical onset by 15 years and concurred with brain atrophy onset, whereas pNfH increase started close to clinical onset. The conversion stage was marked by increased NfL, but still normal pNfH levels, while both were increased at the symptomatic stage. Intra-individual change rates were increased for NfL at the conversion stage and for pNfH at the symptomatic stage, highlighting their respective potential as stage-dependent dynamic biomarkers within the biomarker cascade. Increased NfL levels and NfL change rates allowed identification of presymptomatic subjects converting to symptomatic disease and capture of proximity-to-onset. We estimate stage-dependent sample sizes for trials aiming to decrease neurofilament levels or change rates. Interpretation: Blood NfL and pNfH provide dynamic stage-dependent stratification and, potentially, treatment response biomarkers in presymptomatic FTD, allowing demarcation of the conversion stage. The proposed biomarker cascade might pave the way towards a biomarker-based precision medicine approach to genetic FTD. ANN NEUROL 2022;91:33–47

The Pandora SmallSat: Multiwavelength Characterization of Exoplanets and their Host Stars

Pandora is a SmallSat mission concept, selected as part of NASA’s Astrophysics Pioneers Program, designed to study the atmospheres of exoplanets using transmission spectroscopy. Transmission spectroscopy of transiting exoplanets provides our best opportunity to identify the makeup of planetary atmospheres in the coming decade. Stellar brightness variations due to star spots, however, can seep into these measurements and contaminate the observed spectra. Pandora is designed to disentangle star and planet signals in transmission spectra and reliably characterize the planetary atmospheres. Pandora will collect long-duration photometric observations with a visible-light channel, and simultaneous spectra with a near-IR channel, where water is a strong molecular absorber. The broad wavelength coverage will provide constraints on spot covering fractions of the stars and determine the impact of these active regions on the planetary spectra. Pandora will observe at least 20 exoplanets with sizes ranging from Earth-size to Jupiter-size, with host stars spanning mid-K to late-M spectral types. The project is made possible by leveraging investments in other projects, including an all-aluminum 0.45-meter Cassegrain telescope design, and an IR sensor chip assembly from the James Webb Space Telescope. The mission will last five years from initial formulation to closeout, with one-year of science operations. Launch is planned for the mid-2020s as a secondary payload in Sun-synchronous low-Earth orbit. By design, Pandora has a diverse team, with over half of mission leadership roles filled by early career scientists and engineers, demonstrating the high value of SmallSats for developing the next generation of space mission leaders