Publications

We propose Pathfinder, a variational method for approximately sampling from differentiable log densities. Starting from a random initialization, Pathfinder locates normal approximations to the target density along a quasi-Newton optimization path, with local covariance estimated using the inverse Hessian estimates produced by the optimizer. Pathfinder returns draws from the approximation with the lowest estimated Kullback-Leibler (KL) divergence to the true posterior. We evaluate Pathfinder on a wide range of posterior distributions, demonstrating that its approximate draws are better than those from automatic differentiation variational inference (ADVI) and comparable to those produced by short chains of dynamic Hamiltonian Monte Carlo (HMC), as measured by 1-Wasserstein distance. Compared to ADVI and short dynamic HMC runs, Pathfinder requires one to two orders of magnitude fewer log density and gradient evaluations, with greater reductions for more challenging posteriors. Importance resampling over multiple runs of Pathfinder improves the diversity of approximate draws, reducing 1-Wasserstein distance further and providing a measure of robustness to optimization failures on plateaus, saddle points, or in minor modes. The Monte Carlo KL divergence estimates are embarrassingly parallelizable in the core Pathfinder algorithm, as are multiple runs in the resampling version, further increasing Pathfinder's speed advantage with multiple cores.

We employ machine learning to decode the composition of unknown gas mixtures from the output of an array of four electrochemical sensors. The sensors use metal oxide electrodes paired with a ceramic electrolyte, yttria-stabilized zirconia (YSZ), to produce voltage responses to the presence of gases in complex mixtures. The voltages from the sensor array serve as inputs to a machine learning pipeline which first carries out multi-class classification of mixtures into types based on which gases are present at non-zero concentrations, and subsequently predicts gas concentrations given the mixture type. Thus, our model is able to take a single reading from the sensor array in response to gas mixtures involving NO, NO2, C3H8, and NH3, and output a highly accurate prediction of which gases are present in the mixture, along with the concentrations of each constituent gas. Our computational framework can be easily expanded to include additional gases and additional mixture types, allowing it to be used in numerous automotive, industrial and environmental monitoring settings.

Continuum kinetic theories provide an important tool for the analysis and simulation of particle suspensions. When those particles are anisotropic, the addition of a particle orientation vector to the kinetic description yields a dimensional theory which becomes intractable to simulate, especially in three dimensions or near states where the particles are highly aligned. Coarse-grained theories that track only moments of the particle distribution functions provide a more efficient simulation framework, but require closure assumptions. For the particular case where the particles are apolar, the Bingham closure has been found to agree well with the underlying kinetic theory; yet the closure is non-trivial to compute, requiring the solution of an often nearly-singular nonlinear equation at every spatial discretization point at every timestep. In this paper, we present a robust, accurate, and efficient numerical scheme for evaluating the Bingham closure, with a controllable error/efficiency tradeoff. To demonstrate the utility of the method, we carry out high-resolution simulations of a coarse-grained continuum model for a suspension of active particles in parameter regimes inaccessible to kinetic theories. Analysis of these simulations reveals that inaccurately computing the closure can act to effectively limit spatial resolution in the coarse-grained fields. Pushing these simulations to the high spatial resolutions enabled by our method reveals a coupling between vorticity and topological defects in the suspension director field, as well as signatures of energy transfer between scales in this active fluid model.

Neurons from layer II of the entorhinal cortex (ECII) are the first to accumulate tau protein aggregates and degenerate during prodromal Alzheimer’s disease. Here, we use a data-driven functional genomics approach to model ECII neurons in silico and identify the proto-oncogene DEK as a potential driver of tau pathology. By modulating DEK levels in EC neurons in vitro and in vivo, we first validate the accuracy and cell-type specificity of our network predictions. We then show that Dek silencing changes the inducibility of immediate early genes and alters neuron excitability, leading to dysregulation of neuronal plasticity genes. We further find that loss of function of DEK leads to tau accumulation in the soma of ECII neurons, reactivity of surrounding microglia, and eventually microglia-mediated neuron loss. This study validates a pathological gene discovery tool that opens new therapeutic avenues and sheds light on a novel pathway driving tau pathology in vulnerable neurons.

An ensemble of chemical abundances probing different nucleosynthetic channels can be leveraged to build a comprehensive understanding of the chemical and structural evolution of the Galaxy. Using GALAH DR3 data, we seek to trace the enrichment by the supernovae Ia, supernovae II, asymptotic giant branch stars, and neutron-star mergers and/or collapsars nucleosynthetic sources by studying the [Fe/H], [α/Fe], [Ba/Fe], and [Eu/Fe] chemical compositions of ∼50 000 red giant stars, respectively. Employing small [Fe/H]–[α/Fe] cells, which serve as an effective reference-frame of supernovae contributions, we characterize the abundance-age profiles for [Ba/Fe] and [Eu/Fe]. Our results disclose that these age–abundance relations vary across the [Fe/H]–[α/Fe] plane. Within cells, we find negative age–[Ba/Fe] relations and flat age–[Eu/Fe] relations. Across cells, we see the slope of the age–[Ba/Fe] relations evolve smoothly and the [Eu/Fe] relations vary in amplitude. We subsequently model our empirical findings in a theoretical setting using the flexible Chempy Galactic chemical evolution (GCE) code, using the mean [Fe/H], [Mg/Fe], [Ba/Fe], and age values for stellar populations binned in [Fe/H], [Mg/Fe], and age space. We find that within a one-zone framework, an ensemble of GCE model parameters vary to explain the data. Using present day orbits from Gaia EDR3 measurements we infer that the GCE model parameters, which set the observed chemical abundance distributions, vary systematically across mean orbital radii. Under our modelling assumptions, the observed chemical abundances are consistent with a small gradient in the high-mass end of the initial mass function (IMF) across the disc, where the IMF is more top heavy towards the inner disc and more bottom heavy in the outer disc.

This paper describes the first all-sky search for long-duration, quasi-monochromatic gravitational-wave signals emitted by ultralight scalar boson clouds around spinning black holes using data from the third observing run of Advanced LIGO. We analyze the frequency range from 20~Hz to 610~Hz, over a small frequency derivative range around zero, and use multiple frequency resolutions to be robust towards possible signal frequency wanderings. Outliers from this search are followed up using two different methods, one more suitable for nearly monochromatic signals, and the other more robust towards frequency fluctuations. We do not find any evidence for such signals and set upper limits on the signal strain amplitude, the most stringent being ≈10−25 at around 130~Hz. We interpret these upper limits as both an "exclusion region" in the boson mass/black hole mass plane and the maximum detectable distance for a given boson mass, based on an assumption of the age of the black hole/boson cloud system.

The ensemble of chemical element abundance measurements for stars, along with precision distances and orbit properties, provides high-dimensional data to study the evolution of the Milky Way. With this third data release of the Galactic Archaeology with HERMES (GALAH) survey, we publish 678 423 spectra for 588 571 mostly nearby stars (81.2 percent of stars are within <2 kpc), observed with the HERMES spectrograph at the Anglo-Australian Telescope. This release (hereafter GALAH+ DR3) includes all observations from GALAH Phase 1 (bright, main, and faint survey, 70 percent), K2-HERMES (17 percent), TESS-HERMES (5 percent), and a subset of ancillary observations (8 percent) including the bulge and >75 stellar clusters. We derive stellar parameters Teff, log g, [Fe/H], vmic, vbroad, and vrad using our modified version of the spectrum synthesis code Spectroscopy Made Easy (SME) and 1D MARCS model atmospheres. We break spectroscopic degeneracies in our spectrum analysis with astrometry from Gaia DR2 and photometry from 2MASS. We report abundance ratios [X/Fe] for 30 different elements (11 of which are based on non-LTE computations) covering five nucleosynthetic pathways. We describe validations for accuracy and precision, flagging of peculiar stars/measurements and recommendations for using our results. Our catalogue comprises 65 percent dwarfs, 34 percent giants, and 1 percent other/unclassified stars. Based on unflagged chemical composition and age, we find 62 percent young low-α⁠, 9 percent young high-α⁠, 27 percent old high-α⁠, and 2 percent stars with [Fe/H] ≤ −1. Based on kinematics, 4 percent are halo stars. Several Value-Added-Catalogues, including stellar ages and dynamics, updated after Gaia eDR3, accompany this release and allow chrono-chemodynamic analyses, as we showcase.

Labeled protein-based biomaterials have become popular for various biomedical applications such as tissue-engineered, therapeutic, and diagnostic scaffolds. Labeling of protein biomaterials, including with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles, has enabled a wide variety of imaging and therapeutic techniques. These USPIO-based biomaterials are widely studied in magnetic resonance imaging (MRI), thermotherapy, and magnetically-driven drug delivery, which provide a method for direct and non-invasive monitoring of implants or drug delivery agents. Where most developments have been made using polymers or collagen hydrogels, shown here is the use of a rationally designed protein as the building block for a meso-scale fiber. While USPIOs have been chemically conjugated to antibodies, glycoproteins, and tissue-engineered scaffolds for targeting or improved biocompatibility and stability, these constructs have predominantly served as diagnostic agents and often involve harsh conditions for USPIO synthesis. Here, we present an engineered protein–iron oxide hybrid material comprised of an azide-functionalized coiled-coil protein with small molecule binding capacity conjugated via bioorthogonal azide–alkyne cycloaddition to an alkyne-bearing iron oxide templating peptide, CMms6, for USPIO biomineralization under mild conditions. The coiled-coil protein, dubbed Q, has been previously shown to form nanofibers and, upon small molecule binding, further assembles into mesofibers via encapsulation and aggregation. The resulting hybrid material is capable of doxorubicin encapsulation as well as sensitive weighted MRI darkening for strong imaging capability that is uniquely derived from a coiled-coil protein.

The alignment of planetary orbits with respect to the stellar rotation preserves information on their dynamical histories. Measuring this angle for young planets help illuminate the mechanisms that create misaligned orbits for older planets, as different processes could operate over timescales ranging from a few Myr to a Gyr. We present spectroscopic transit observations of the young exoplanet V1298 Tau b; we update the age of V1298 Tau to be 28±4 Myr based on Gaia EDR3 measurements. We observed a partial transit with Keck/HIRES and LBT/PEPSI, and detected the radial velocity anomaly due to the Rossiter-McLaughlin effect. V1298 Tau~b has a prograde, well-aligned orbit, with λ=4+7∘−10. By combining the spectroscopically-measured vsini⋆ and the phtometrically-measured rotation period of the host star we also find that the orbit is aligned in 3D, ψ=8+4∘−7 deg. Finally, we combine our obliquity constraints with a previous measurement for the interior planet V1298 Tau c to constrain the mutual inclination between the two planets to be imut=0∘±19∘. This measurements adds to the growing number of well-aligned planets at young ages, hinting that misalignments may be generated over timescales of longer than tens of Myr. The number of measurements, however, is still small, and this population may not be representative of the older planets that have been observed to date. We also present the derivation of the relationship between imut, λ, and i for two planets.

We present a spectrally accurate embedded boundary method for solving linear, inhomogeneous, elliptic partial differential equations (PDE) in general smooth geometries, focusing in this manuscript on the Poisson, modified Helmholtz, and Stokes equations. Unlike several recently proposed methods which rely on function extension, we propose a method which instead utilizes function `intension', or the smooth truncation of known function values. Similar to those methods based on extension, once the inhomogeneity is truncated we may solve the PDE using any of the many simple, fast, and robust solvers that have been developed for regular grids on simple domains. Function intension is inherently stable, as are all steps in the proposed solution method, and can be used on domains which do not readily admit extensions. We pay a price in exchange for improved stability and flexibility: in addition to solving the PDE on the regular domain, we must additionally (1) solve the PDE on a small auxiliary domain that is fitted to the boundary, and (2) ensure consistency of the solution across the interface between this auxiliary domain and the rest of the physical domain. We show how these tasks may be accomplished efficiently (in both the asymptotic and practical sense), and compare convergence to several recent high-order embedded boundary schemes.