Inference of single-cell phylogenies from lineage tracing data using Cassiopeia.

The pairing of CRISPR/Cas9-based gene editing with massively parallel single-cell readouts now enables large-scale lineage tracing. However, the rapid growth in complexity of data from these assays has outpaced our ability to accurately infer phylogenetic relationships. First, we introduce Cassiopeia-a suite of scalable maximum parsimony approaches for tree reconstruction. Second, we provide a simulation framework for evaluating algorithms and exploring lineage tracer design principles. Finally, we generate the most complex experimental lineage tracing dataset to date, 34,557 human cells continuously traced over 15 generations, and use it for benchmarking phylogenetic inference approaches. We show that Cassiopeia outperforms traditional methods by several metrics and under a wide variety of parameter regimes, and provide insight into the principles for the design of improved Cas9-enabled recorders. Together, these should broadly enable large-scale mammalian lineage tracing efforts. Cassiopeia and its benchmarking resources are publicly available at www.github.com/YosefLab/Cassiopeia

Multiple episodes of star formation in the CN15/16/17 molecular complex

We have started a campaign to identify massive star clusters inside bright molecular bubbles towards the Galactic Center. The CN15/16/17 molecular complex is the first example of our study. The region is characterized by the presence of two young clusters, DB10 and DB11, visible in the NIR, an ultra-compact HII region identified in the radio, several young stellar objects visible in the MIR, a bright diffuse nebulosity at 8\mu m coming from PAHs and sub-mm continuum emission revealing the presence of cold dust. Given its position on the sky (l=0.58, b=-0.85) and its kinematic distance of ~7.5 kpc, the region was thought to be a very massive site of star formation in proximity of the CMZ. The cluster DB11 was estimated to be as massive as 10^4 M_sun. However the region's properties were known only through photometry and its kinematic distance was very uncertain given its location at the tangential point. We aimed at better characterizing the region and assess whether it could be a site of massive star formation located close to the Galactic Center. We have obtained NTT/SofI JHKs photometry and long slit K band spectroscopy of the brightest members. We have additionally collected data in the radio, sub-mm and mid infrared, resulting in a quite different picture of the region. We have confirmed the presence of massive early B type stars and have derived a spectro-photometric distance of ~1.2 kpc, much smaller than the kinematic distance. Adopting this distance we obtain clusters masses of M(DB10) ~ 170 M_sun and M(DB11) ~ 275 M_sun. This is consistent with the absence of any O star, confirmed by the excitation/ionization status of the nebula. No HeI diffuse emission is detected in our spectroscopic observations at 2.113\mu m, which would be expected if the region was hosting more massive stars. Radio continuum measurements are also consistent with the region hosting at most early B stars.Comment: Accepted for publication in Astronomy and Astrophysics. Fig. 1 and 3 presented in reduced resolutio

A New Radioligand Binding Assay to Measure the Concentration of Drugs in Rodent Brain Ex Vivo

ABSTRACT We have developed a new radioligand binding assay method to measure the concentration of nonradiolabeled drugs in the brain ex vivo. This new method fuses the concepts of standard competition and saturation binding assays and uses a transformed version of the Cheng-Prusoff equation (Biochem Pharmacol 22: 3099 -3108, 1973) to calculate the drug concentration. After testing the validity of this method, we demonstrated its utility by measuring the brain concentration of sazetidine-A, a newly developed nicotinic receptor ligand, and its elimination rate after a single subcutaneous administration. Our results indicate that sazetidine-A reaches brain concentrations that are known to occupy and desensitize the majority of neuronal nicotinic acetylcholine receptor binding sites. Furthermore, using this method, we estimated the half-life of sazetidine-A in the rat brain to be ϳ65 min. It is important to note that the method described here to measure sazetidine-A in brain should be generalizable to other drugs acting at any receptor that can be reliably measured with a radiolabeled ligand

Tidal friction in close-in satellites and exoplanets. The Darwin theory re-visited

This report is a review of Darwin's classical theory of bodily tides in which we present the analytical expressions for the orbital and rotational evolution of the bodies and for the energy dissipation rates due to their tidal interaction. General formulas are given which do not depend on any assumption linking the tidal lags to the frequencies of the corresponding tidal waves (except that equal frequency harmonics are assumed to span equal lags). Emphasis is given to the cases of companions having reached one of the two possible final states: (1) the super-synchronous stationary rotation resulting from the vanishing of the average tidal torque; (2) the capture into a 1:1 spin-orbit resonance (true synchronization). In these cases, the energy dissipation is controlled by the tidal harmonic with period equal to the orbital period (instead of the semi-diurnal tide) and the singularity due to the vanishing of the geometric phase lag does not exist. It is also shown that the true synchronization with non-zero eccentricity is only possible if an extra torque exists opposite to the tidal torque. The theory is developed assuming that this additional torque is produced by an equatorial permanent asymmetry in the companion. The results are model-dependent and the theory is developed only to the second degree in eccentricity and inclination (obliquity). It can easily be extended to higher orders, but formal accuracy will not be a real improvement as long as the physics of the processes leading to tidal lags is not better known.Comment: 30 pages, 7 figures, corrected typo

Constraining Ceres' interior from its Rotational Motion

Context. Ceres is the most massive body of the asteroid belt and contains about 25 wt.% (weight percent) of water. Understanding its thermal evolution and assessing its current state are major goals of the Dawn Mission. Constraints on internal structure can be inferred from various observations. Especially, detailed knowledge of the rotational motion can help constrain the mass distribution inside the body, which in turn can lead to information on its geophysical history. Aims. We investigate the signature of the interior on the rotational motion of Ceres and discuss possible future measurements performed by the spacecraft Dawn that will help to constrain Ceres' internal structure. Methods. We compute the polar motion, precession-nutation, and length-of-day variations. We estimate the amplitudes of the rigid and non-rigid response for these various motions for models of Ceres interior constrained by recent shape data and surface properties. Results. As a general result, the amplitudes of oscillations in the rotation appear to be small, and their determination from spaceborne techniques will be challenging. For example, the amplitudes of the semi-annual and annual nutations are around ~364 and ~140 milli-arcseconds, and they show little variation within the parametric space of interior models envisioned for Ceres. This, combined with the very long-period of the precession motion, requires very precise measurements. We also estimate the timescale for Ceres' orientation to relax to a generalized Cassini State, and we find that the tidal dissipation within that object was probably too small to drive any significant damping of its obliquity since formation. However, combining the shape and gravity observations by Dawn offers the prospect to identify departures of non-hydrostaticity at the global and regional scale, which will be instrumental in constraining Ceres' past and current thermal state. We also discuss the existence of a possible Chandler mode in the rotational motion of Ceres, whose potential excitation by endogenic and/or exogenic processes may help detect the presence of liquid reservoirs within the asteroid.Comment: submitted to Astronomy and Astrophysic

The Europa Clipper Gravity and Radio Science Investigation

The primary objective of the Europa Clipper mission is to assess the habitability of Europa, an overarching goal that rests on improving our understanding of Europa’s interior structure, composition, and geologic activity. Here we describe the Gravity and Radio Science (G/RS) investigation. The primary measurement, the gravitational tidal Love number k2 , will be an independent diagnostic of the presence of a global subsurface ocean, but G/RS will make a number of other key measurements related to Europa’s deep interior, silicate mantle-ocean interface, ice shell, ionosphere, and plasma environment. Although radio science is common to many missions, Europa Clipper’s orbit and spacecraft configuration during flybys present special challenges for the design of this experiment. The information obtained through G/RS will be complementary to the measurements by the other instruments onboard Europa Clipper, and their combined analysis will refine the geophysical understanding of Europa necessary to best assess its potential habitability

Stability of Terrestrial Planets in the Habitable Zone of Gl 777 A, HD 72659, Gl 614, 47 Uma and HD 4208

We have undertaken a thorough dynamical investigation of five extrasolar planetary systems using extensive numerical experiments. The systems Gl 777 A, HD 72659, Gl 614, 47 Uma and HD 4208 were examined concerning the question of whether they could host terrestrial like planets in their habitable zones (=HZ). First we investigated the mean motion resonances between fictitious terrestrial planets and the existing gas giants in these five extrasolar systems. Then a fine grid of initial conditions for a potential terrestrial planet within the HZ was chosen for each system, from which the stability of orbits was then assessed by direct integrations over a time interval of 1 million years. The computations were carried out using a Lie-series integration method with an adaptive step size control. This integration method achieves machine precision accuracy in a highly efficient and robust way, requiring no special adjustments when the orbits have large eccentricities. The stability of orbits was examined with a determination of the Renyi entropy, estimated from recurrence plots, and with a more straight forward method based on the maximum eccentricity achieved by the planet over the 1 million year integration. Additionally, the eccentricity is an indication of the habitability of a terrestrial planet in the HZ; any value of e>0.2 produces a significant temperature difference on a planet's surface between apoapse and periapse. The results for possible stable orbits for terrestrial planets in habitable zones for the five systems are summarized as follows: for Gl 777 A nearly the entire HZ is stable, for 47 Uma, HD 72659 and HD 4208 terrestrial planets can survive for a sufficiently long time, while for Gl 614 our results exclude terrestrial planets moving in stable orbits within the HZ.Comment: 14 pages, 18 figures submitted to A&

Modeling magnetospheric fields in the Jupiter system

The various processes which generate magnetic fields within the Jupiter system are exemplary for a large class of similar processes occurring at other planets in the solar system, but also around extrasolar planets. Jupiter's large internal dynamo magnetic field generates a gigantic magnetosphere, which is strongly rotational driven and possesses large plasma sources located deeply within the magnetosphere. The combination of the latter two effects is the primary reason for Jupiter's main auroral ovals. Jupiter's moon Ganymede is the only known moon with an intrinsic dynamo magnetic field, which generates a mini-magnetosphere located within Jupiter's larger magnetosphere including two auroral ovals. Ganymede's magnetosphere is qualitatively different compared to the one from Jupiter. It possesses no bow shock but develops Alfv\'en wings similar to most of the extrasolar planets which orbit their host stars within 0.1 AU. New numerical models of Jupiter's and Ganymede's magnetospheres presented here provide quantitative insight into the processes that maintain these magnetospheres. Jupiter's magnetospheric field is approximately time-periodic at the locations of Jupiter's moons and induces secondary magnetic fields in electrically conductive layers such as subsurface oceans. In the case of Ganymede, these secondary magnetic fields influence the oscillation of the location of its auroral ovals. Based on dedicated Hubble Space Telescope observations, an analysis of the amplitudes of the auroral oscillations provides evidence that Ganymede harbors a subsurface ocean. Callisto in contrast does not possess a mini-magnetosphere, but still shows a perturbed magnetic field environment. Callisto's ionosphere and atmospheric UV emission is different compared to the other Galilean satellites as it is primarily been generated by solar photons compared to magnetospheric electrons.Comment: Chapter for Book: Planetary Magnetis

Ice Lines, Planetesimal Composition and Solid Surface Density in the Solar Nebula

To date, there is no core accretion simulation that can successfully account for the formation of Uranus or Neptune within the observed 2-3 Myr lifetimes of protoplanetary disks. Since solid accretion rate is directly proportional to the available planetesimal surface density, one way to speed up planet formation is to take a full accounting of all the planetesimal-forming solids present in the solar nebula. By combining a viscously evolving protostellar disk with a kinetic model of ice formation, we calculate the solid surface density in the solar nebula as a function of heliocentric distance and time. We find three effects that strongly favor giant planet formation: (1) a decretion flow that brings mass from the inner solar nebula to the giant planet-forming region, (2) recent lab results (Collings et al. 2004) showing that the ammonia and water ice lines should coincide, and (3) the presence of a substantial amount of methane ice in the trans-Saturnian region. Our results show higher solid surface densities than assumed in the core accretion models of Pollack et al. (1996) by a factor of 3 to 4 throughout the trans-Saturnian region. We also discuss the location of ice lines and their movement through the solar nebula, and provide new constraints on the possible initial disk configurations from gravitational stability arguments.Comment: Version 2: reflects lead author's name and affiliation change, contains minor changes to text from version 1. 12 figures, 7 tables, accepted for publication in Icaru

The BepiColombo Laser Altimeter (BELA) during Near-Earth Commissioning Phase (NECP)

The ESA/JAXA joint mission BepiColombo to Mercury was launched successfully on October 20, 2018 (UTC) from Kourou, French Guiana. Currently BepiColombo is on its nominal 7-years cruise to the innermost planet. BepiColombo consists of two spacecraft, the Mercury Planetary Orbiter (MPO) and the Mercury Magnetospheric Orbiter (MMO), both targeted for different orbits around Mercury after arrival in December 2025. The BepiColombo Laser Altimeter (BELA) is one of ten payloads on the MPO. After launch the spacecraft and the instruments entered the Near-Earth Commissioning Phase (NECP), including a first switch-on of BELA on November24, 2018. Here we report on the status of the instrument based on the analysis of NECP data and on data from a second switch-on, planned for June 2019