Publications

Cortical pyramidal neurons receive inputs from multiple distinct neural populations and integrate these inputs in separate dendritic compartments. We explore the possibility that cortical microcircuits implement canonical correlation analysis (CCA), an unsupervised learning method that projects the inputs onto a common subspace so as to maximize the correlations between the projections. To this end, we seek a multichannel CCA algorithm that can be implemented in a biologically plausible neural network. For biological plausibility, we require that the network operates in the online setting and its synaptic update rules are local. Starting from a novel CCA objective function, we derive an online optimization algorithm whose optimization steps can be implemented in a single-layer neural network with multicompartmental neurons and local non-Hebbian learning rules. We also derive an extension of our online CCA algorithm with adaptive output rank and output whitening. Interestingly, the extension maps onto a neural network whose neural architecture and synaptic updates resemble neural circuitry and non-Hebbian plasticity observed in the cortex.

The simplest scheme for predicting real galaxy properties after performing a dark matter simulation is to rank order the real systems by stellar mass and the simulated systems by halo mass and then simply assume monotonicity - that the more massive halos host the more massive galaxies. This has had some success, but we study here if a better motivated and more accurate matching scheme is easily constructed by looking carefully at how well one could predict the simulated IllustrisTNG galaxy sample from its dark matter computations. We find that using the dark matter rotation curve peak velocity, vmax, for normal galaxies reduces the error of the prediction by 30% (18% for central galaxies and 60% for satellite systems) - following expectations from the physics of monolithic collapse. For massive systems with halo mass > 1012.5 M⊙ hierarchical merger driven formation is the better model and dark matter halo mass remains the best single metric. Using a new single variable that combines these effects, ϕ = vmax/vmax,12.7 + Mpeak/(1012.7 M⊙) allows further improvement and reduces the error, as compared to ranking by dark matter mass at z=0 by another 6% from vmax ranking. Two parameter fits -- including environmental effects produce only minimal further impact.

Anomalies among the daughter nuclei of the extinct short-lived radionuclides (SLRs) in the calcium-aluminum-rich inclusions (CAIs) indicate that the Solar System must have been born near a source of the SLRs so that they could be incorporated before they decayed away. γ-rays from one such living SLR, 26Al, are detected in only a few nearby star-forming regions. Here we employ multi-wavelength observations to demonstrate that one such region, Ophiuchus, containing many pre-stellar cores that may serve as analogs for the emerging Solar System, is inundated with 26Al from the neighboring Upper-Scorpius association, and so may provide concrete guidance for how SLR enrichment proceeded in the Solar System complementary to the meteoritics. We demonstrate via Bayesian forward modeling drawing on a wide range of observational and theoretical results that this 26Al likely 1) arises from supernova explosions, 2) arises from multiple stars, 3) has enriched the gas prior to the formation of the cores, and 4) gives rise to a broad distribution of core enrichment spanning about two orders of magnitude. This means that if the spread in CAI ages is small, as it is in the Solar System, protoplanetary disks must suffer a global heating event.

Phase retrieval is the inverse problem of recovering a signal from magnitude-only Fourier measurements, and underlies numerous imaging modalities, such as Coherent Diffraction Imaging (CDI). A variant of this setup, known as holography, includes a reference object that is placed adjacent to the specimen of interest before measurements are collected. The resulting inverse problem, known as holographic phase retrieval, is well-known to have improved problem conditioning relative to the original. This innovation, i.e. Holographic CDI, becomes crucial at the nanoscale, where imaging specimens such as viruses, proteins, and crystals require low-photon measurements. This data is highly corrupted by Poisson shot noise, and often lacks low-frequency content as well. In this work, we introduce a dataset-free deep learning framework for holographic phase retrieval adapted to these challenges. The key ingredients of our approach are the explicit and flexible incorporation of the physical forward model into an automatic differentiation procedure, the Poisson log-likelihood objective function, and an optional untrained deep image prior. We perform extensive evaluation under realistic conditions. Compared to competing classical methods, our method recovers signal from higher noise levels and is more resilient to suboptimal reference design, as well as to large missing regions of low frequencies in the observations. To the best of our knowledge, this is the first work to consider a dataset-free machine learning approach for holographic phase retrieval.

Accretion disks around supermassive black holes in active galactic nuclei produce continuum radiation at ultraviolet and optical wavelengths. Physical processes in the accretion flow lead to stochastic variability of this emission on a wide range of time scales. We measured the optical continuum variability observed in 67 active galactic nuclei and the characteristic time scale at which the variability power spectrum flattens. We found a correlation between this time scale and the black hole mass extending over the entire mass range of supermassive black holes. This time scale is consistent with the expected thermal time scale at the ultraviolet-emitting radius in standard accretion disk theory. Accreting white dwarfs lie close to this correlation, suggesting a common process for all accretion disks.

In cellular vortical flows, namely arrays of counterrotating vortices, short but flexible filaments can show simple random walks through their stretch-coil interactions with flow stagnation points. Here, we study the dynamics of semirigid filaments long enough to broadly sample the vortical field. Using simulation, we find a surprising variety of long-time transport behavior—random walks, ballistic transport, and trapping—depending upon the filament’s relative length and effective flexibility. Moreover, we find that filaments execute Lévy walks whose diffusion exponents generally decrease with increasing filament length, until transitioning to Brownian walks. Lyapunov exponents likewise increase with length. Even completely rigid filaments, whose dynamics is finite dimensional, show a surprising variety of transport states and chaos. Fast filament dispersal is related to an underlying geometry of “conveyor belts.” Evidence for these various transport states is found in experiments using arrays of counterrotating rollers, immersed in a fluid and transporting a flexible ribbon.

There is a shortage of multiwavelength and spectroscopic follow-up capabilities given the number of transient and variable astrophysical events discovered through wide-field optical surveys such as the upcoming Vera C. Rubin Observatory and its associated Legacy Survey of Space and Time. From the haystack of potential science targets, astronomers must allocate scarce resources to study a selection of needles in real time. Here we present a variational recurrent autoencoder neural network to encode simulated Rubin Observatory extragalactic transient events using 1% of the PLAsTiCC data set to train the autoencoder. Our unsupervised method uniquely works with unlabeled, real-time, multivariate, and aperiodic data. We rank 1,129,184 events based on an anomaly score estimated using an isolation forest. We find that our pipeline successfully ranks rarer classes of transients as more anomalous. Using simple cuts in anomaly score and uncertainty, we identify a pure (≈95% pure) sample of rare transients (i.e., transients other than Type Ia, Type II, and Type Ibc supernovae), including superluminous and pair-instability supernovae. Finally, our algorithm is able to identify these transients as anomalous well before peak, enabling real-time follow-up studies in the era of the Rubin Observatory.

Mixtures of microtubules and molecular motors form active materials with diverse dynamical behaviors that vary based on their constituents' molecular properties. We map the non-equilibrium phase diagram of microtubules and tip-accumulating kinesin-4 molecular motors. We find that kinesin-4 can drive either global contractions or turbulent-like extensile dynamics, depending on the concentrations of both microtubules and a bundling agent. We also observe a range of spatially heterogeneous non-equilibrium phases, including finite-sized radial asters, 1D wormlike chains, extended 2D bilayers, and system-spanning 3D active foams. Finally, we describe intricate kinetic pathways that yield microphase separated structures and arise from the inherent frustration between the orientational order of filamentous microtubules and the positional order of tip-accumulating molecular motors. Our work shows that the form of active stresses and phases in cytoskeletal networks are not solely dictated by the properties of individual motors and filaments, but are also contingent on the constituent's concentrations and spatial arrangement.

Motile cilia are slender, hair-like cellular appendages that spontaneously oscillate under the action of internal molecular motors and are typically found in dense arrays. These active filaments coordinate their beating to generate metachronal waves that drive long-range fluid transport and locomotion. Until now, our understanding of their collective behavior largely comes from the study of minimal models that coarse-grain the relevant biophysics and the hydrodynamics of slender structures. Here we build on a detailed biophysical model to elucidate the emergence of metachronal waves on millimeter scales from nanometer scale motor activity inside individual cilia. Our study of a 1D lattice of cilia in the presence of hydrodynamic and steric interactions reveals how metachronal waves are formed and maintained. We find that in homogeneous beds of cilia these interactions lead to multiple attracting states, all of which are characterized by an integer charge that is conserved. This even allows us to design initial conditions that lead to predictable emergent states. Finally, and very importantly, we show that in nonuniform ciliary tissues, boundaries and inhomogeneities provide a robust route to metachronal waves.

Tubulin is a well-validated target for herbicides, fungicides, anti-parasitic, and anti-tumor drugs. Many of the non-cancer tubulin drugs bind to its colchicine site but no colchicine-site anticancer drug is available. The colchicine site is composed of three interconnected sub-pockets that fit their ligands and modify others’ preference, making the design of molecular hybrids (that bind to more than one sub-pocket) a difficult task. Taking advantage of the more than eighty published X-ray structures of tubulin in complex with ligands bound to the colchicine site, we generated an ensemble of pharmacophore representations that flexibly sample the interactional space between the ligands and target. We searched the ZINC database for scaffolds able to fit several of the subpockets, such as tetrazoles, sulfonamides and diarylmethanes, selected roughly 8000 compounds with favorable predicted properties. A Flexi-pharma virtual screening, based on ensemble pharmacophore, was performed by two different methodologies. Combining the scaffolds that best fit the ensemble pharmacophore-representation, we designed a new family of ligands, resulting in a novel tubulin modulator. We synthesized tetrazole 5 and tested it as a tubulin inhibitor in vitro. In good agreement with the design principles, it demonstrated micromolar activity against in vitro tubulin polymerization and nanomolar anti-proliferative effect against human epithelioid carcinoma HeLa cells through microtubule disruption, as shown by immunofluorescence confocal microscopy. The integrative methodology succedes in the design of new scaffolds for flexible proteins with structural coupling between pockets, thus expanding the way in which computational methods can be used as significant tools in the drug design process.