Publications

One of the great challenges in biology is to understand the mechanisms by which morphogenetic processes arise from molecular activities. We investigated this problem in the context of actomyosin-based cortical flow in C. elegans zygotes, where large-scale flows emerge from the collective action of actomyosin filaments and actin binding proteins (ABPs). Large-scale flow dynamics can be captured by active gel theory by considering force balances and conservation laws in the actomyosin cortex. However, which molecular activities contribute to flow dynamics and large-scale physical properties such as viscosity and active torque is largely unknown. By performing a candidate RNAi screen of ABPs and actomyosin regulators we demonstrate that perturbing distinct molecular processes can lead to similar flow phenotypes. This is indicative for a 'morphogenetic degeneracy' where multiple molecular processes contribute to the same large-scale physical property. We speculate that morphogenetic degeneracies contribute to the robustness of bulk biological matter in development.

With contemporary infrared spectroscopic surveys like APOGEE, red-giant stars can be observed to distances and extinctions at which Gaia parallaxes are not highly informative. Yet the combination of effective temperature, surface gravity, composition, and age - all accessible through spectroscopy - determines a giant's luminosity. Therefore spectroscopy plus photometry should enable precise spectrophotometric distance estimates. Here we use the APOGEE-Gaia-2MASS-WISE overlap to train a data-driven model to predict parallaxes for red-giant branch stars with 0

We measure the circular velocity curve vc(R) of the Milky Way with the highest precision to date across Galactocentric distances of 5≤R≤25 kpc. Our analysis draws on the 6-dimensional phase-space coordinates of ≳23,000 luminous red-giant stars, for which we previously determined precise parallaxes using a data-driven model that combines spectral data from APOGEE with photometric information from WISE, 2MASS, and Gaia. We derive the circular velocity curve with the Jeans equation assuming an axisymmetric gravitational potential. At the location of the Sun we determine the circular velocity with its formal uncertainty to be vc(R⊙)=(229.0±0.2)kms−1 with systematic uncertainties at the ∼5% level. We find that the velocity curve is gently but significantly declining at (−1.7±0.1)kms−1kpc−1, with a systematic uncertainty of 0.46kms−1kpc−1, beyond the inner 5 kpc. We exclude the inner 5 kpc from our analysis due to the presence of the Galactic bar, which strongly influences the kinematic structure and requires modeling in a non-axisymmetric potential. Combining our results with external measurements of the mass distribution for the baryonic components of the Milky Way from other studies, we estimate the Galaxy's dark halo mass within the virial radius to be Mvir=(7.25±0.26)⋅1011M⊙ and a local dark matter density of ρdm(R⊙)=0.30±0.03GeVcm−3.

Effective discovery of causal disease genes must overcome the statistical challenges of quantitative genetics studies and the practical limitations of human biology experiments. Here we developed diseaseQUEST, an integrative approach that combines data from human genome-wide disease studies with in silico network models of tissue- and cell-type-specific function in model organisms to prioritize candidates within functionally conserved processes and pathways. We used diseaseQUEST to predict candidate genes for 25 different diseases and traits, including cancer, longevity, and neurodegenerative diseases. Focusing on Parkinson's disease (PD), a diseaseQUEST-directed Caenhorhabditis elegans behavioral screen identified several candidate genes, which we experimentally verified and found to be associated with age-dependent motility defects mirroring PD clinical symptoms. Furthermore, knockdown of the top candidate gene, bcat-1, encoding a branched chain amino acid transferase, caused spasm-like 'curling' and neurodegeneration in C. elegans, paralleling decreased BCAT1 expression in PD patient brains. diseaseQUEST is modular and generalizable to other model organisms and human diseases of interest.

Artificial neural networks that learn to perform Principal Component Analysis (PCA) and related tasks using strictly local learning rules have been previously derived based on the principle of similarity matching: similar pairs of inputs should map to similar pairs of outputs. However, the operation of these networks (and of similar networks) requires a fixed-point iteration to determine the output corresponding to a given input, which means that dynamics must operate on a faster time scale than the variation of the input. Further, during these fast dynamics such networks typically "disable" learning, updating synaptic weights only once the fixed-point iteration has been resolved. Here, we derive a network for PCA-based dimensionality reduction that avoids this fast fixed-point iteration. The key novelty of our approach is a modification of the similarity matching objective to encourage near-diagonality of a synaptic weight matrix. We then approximately invert this matrix using a Taylor series approximation, replacing the previous fast iterations. In the offline setting, our algorithm corresponds to a dynamical system, the stability of which we rigorously analyze. In the online setting (i.e., with stochastic gradients), we map our algorithm to a familiar neural network architecture and give numerical results showing that our method converges at a competitive rate. The computational complexity per iteration of our online algorithm is linear in the total degrees of freedom, which is in some sense optimal.

Pulsar timing arrays (PTAs) can be used to detect and study gravitational waves in the nanohertz band (i.e., wavelengths of order light-years). This requires high-precision, decades-long data sets from sensitive, instrumentally stable telescopes. NANOGrav and its collaborators in the International Pulsar Timing Array consortium are on the verge of the first detection of the stochastic background produced by supermassive binary black holes, which form via the mergers of massive galaxies. By providing Northern hemisphere sky coverage with exquisite sensitivity and higher frequency coverage compared to the SKA, a Next-Generation Very Large Array (ngVLA) will be a fundamental component in the next phase of nanohertz GW astrophysics, enabling detailed characterization of the stochastic background and the detection of individual sources contributing to the background, as well as detections of (or stringent constraints on) cosmic strings and other exotica. Here we summarize the scientific goals of PTAs and the technical requirements for the ngVLA to play a significant role in the characterization of the nanohertz gravitational wave universe.

We derive analytic, closed form, numerically stable solutions for the total flux received from a spherical planet, moon or star during an occultation if the specific intensity map of the body is expressed as a sum of spherical harmonics. Our expressions are valid to arbitrary degree and may be computed recursively for speed. The formalism we develop here applies to the computation of stellar transit light curves, planetary secondary eclipse light curves, and planet-planet/planet-moon occultation light curves, as well as thermal (rotational) phase curves. In this paper we also introduce STARRY, an open-source package written in C++ and wrapped in Python that computes these light curves. The algorithm in STARRY is six orders of magnitude faster than direct numerical integration and several orders of magnitude more precise. STARRY also computes analytic derivatives of the light curves with respect to all input parameters for use in gradient-based optimization and inference, such as Hamiltonian Monte Carlo (HMC), allowing users to quickly and efficiently fit observed light curves to infer properties of a celestial body's surface map.

It has been demonstrated that the time variability of a star's brightness at different frequencies can be used to infer its surface gravity, radius, mass, and age. With large samples of light curves now available from Kepler and K2, and upcoming surveys like TESS, we wish to quantify the overall information content of this data and identify where the information resides. As a first look into this question, we ask which stellar parameters we can predict from the brightness variations in red-giant stars data and to what precision, using a data-driven, nonparametric model. We demonstrate that the long-cadence (30 minute) Kepler light curves for 2000 red-giant stars can be used to predict their ${T}_{\mathrm{eff}}$ and $\mathrm{log}g$. Our inference makes use of a data-driven model of a part of the autocorrelation function (ACF) of the light curve, where we posit a polynomial relationship between stellar parameters and the ACF pixel values. We find that this model, trained using 1000 stars, can be used to recover the temperature ${T}_{\mathrm{eff}}$ to <100 K, the surface gravity to <0.1 dex, and the asteroseismic power-spectrum parameters ${\nu }_{\max }$ and ${\rm{\Delta }}\nu $ to <11 μHz and <0.9 μHz (lesssim15%). We recover ${T}_{\mathrm{eff}}$ from range of time lags 0.045 < ${T}_{\mathrm{lag}}$ < 370 days and the $\mathrm{log}g$, ${\nu }_{\max }$, and ${\rm{\Delta }}\nu $ from the range 0.045 < ${T}_{\mathrm{lag}}$ < 35 days. We do not discover any information about stellar metallicity in this model of the ACF. The information content of the data about each parameter is empirically quantified using this method, enabling comparisons to theoretical expectations about convective granulation.

We have recently proposed a nonequilibrium Green’s function (NEGF) approach to include Auger decay processes in the ultrafast charge dynamics of photoionized molecules. Within the so-called generalized Kadanoff–Baym ansatz the fundamental unknowns of the NEGF equations are the reduced one-particle density matrix of bound electrons and the occupations of the continuum states. Both unknowns are one-time functions like the density in time-dependent functional theory (TDDFT). In this work, we assess the accuracy of the approach against configuration interaction (CI) calculations in one-dimensional model systems. Our results show that NEGF correctly captures qualitative and quantitative features of the relaxation dynamics provided that the energy of the Auger electron is much larger than the Coulomb repulsion between two holes in the valence shells. For the accuracy of the results dynamical electron-electron correlations or, equivalently, memory effects play a pivotal role. The combination of our NEGF approach with the Sham–Schlüter equation may provide useful insights for the development of TDDFT exchange-correlation potentials with a history dependence.