Publications

During early Drosophila embryogenesis, a network of gene regulatory interactions orchestrates terminal patterning, playing a critical role in the subsequent formation of the gut. We utilized CRISPR gene editing at endogenous loci to create live reporters of transcription and light-sheet microscopy to monitor the individual components of the posterior gut patterning network across 90 min prior to gastrulation. We developed a computational approach for fusing imaging datasets of the individual components into a common multivariable trajectory. Data fusion revealed low intrinsic dimensionality of posterior patterning and cell fate specification in wild-type embryos. The simple structure that we uncovered allowed us to construct a model of interactions within the posterior patterning regulatory network and make testable predictions about its dynamics at the protein level. The presented data fusion strategy is a step toward establishing a unified framework that would explore how stochastic spatiotemporal signals give rise to highly reproducible morphogenetic outcomes.

The SPT0311-58 system at z=6.900 is an extremely massive structure within the reionization epoch, and offers a chance to understand the formation of galaxies in an extreme peak in the primordial density field. We present 70mas Atacama Large Millimeter/submillimeter Array observations of the dust continuum and CII 158um emission in the central pair of galaxies and reach physical resolution ~100-350pc, among the most detailed views of any reionization-era system to date. The observations resolve the source into at least a dozen kiloparsec-size clumps. The global kinematics and high turbulent velocity dispersion within the galaxies present a striking contrast to recent claims of dynamically cold thin-disk kinematics in some dusty galaxies just 800Myr later at z~4. We speculate that both gravitational interactions and fragmentation from massive parent disks have likely played a role in the overall dynamics and formation of clumps in the system. Each clump individually is comparable in mass to other 6<z<8 galaxies identified in rest-UV/optical deep field surveys, but with star formation rates elevated by ~3-5x. Internally, the clumps themselves bear close resemblance to greatly scaled-up versions of virialized cloud-scale structures identified in low-redshift galaxies. Our observations are qualitatively similar to the chaotic and clumpy assembly within massive halos seen in simulations of high-redshift galaxies.

Young adults infected with SARS-CoV-2 are frequently asymptomatic or develop only mild disease. Because capturing representative mild and asymptomatic cases require active surveillance, they are less characterized than moderate or severe cases of COVID-19. However, a better understanding of SARS-CoV-2 asymptomatic infections might shed light into the immune mechanisms associated with the control of symptoms and protection. To this aim, we have determined the temporal dynamics of the humoral immune response, as well as the serum inflammatory profile, of mild and asymptomatic SARS-CoV-2 infections in a cohort of 172 initially seronegative prospectively studied United States Marine recruits, 149 of whom were subsequently found to be SARS-CoV-2 infected. The participants had blood samples taken, symptoms surveyed and PCR tests for SARS-CoV-2 performed periodically for up to 105 days. We found similar dynamics in the profiles of viral load and in the generation of specific antibody responses in asymptomatic and mild symptomatic participants. A proteomic analysis using an inflammatory panel including 92 analytes revealed a pattern of three temporal waves of inflammatory and immunoregulatory mediators, and a return to baseline for most of the inflammatory markers by 35 days post-infection. We found that 23 analytes were significantly higher in those participants that reported symptoms at the time of the first positive SARS-CoV-2 PCR compared with asymptomatic participants, including mostly chemokines and cytokines associated with inflammatory response or immune activation (i.e., TNF-α, TNF-β, CXCL10, IL-8). Notably, we detected 7 analytes (IL-17C, MMP-10, FGF-19, FGF-21, FGF-23, CXCL5 and CCL23) that were higher in asymptomatic participants than in participants with symptoms; these are known to be involved in tissue repair and may be related to the control of symptoms. Overall, we found a serum proteomic signature that differentiates asymptomatic and mild symptomatic infections in young adults, including potential targets for developing new therapies and prognostic tests.

In their recent paper [Phys. Rev. A 103, 043106 (2021)], Zang et al. theoretically investigated high harmonic generation (HHG) in benchmark two-electron systems that are inversion symmetric with time-dependent density functional theory (TDDFT) in the Kohn-Sham formulation. They found that the theory wrongly predicted the emission of symmetry-forbidden even harmonics and concluded that this error originates from an inherent problem of TDDFT that unphysically populates one- and two-electron excited states. They further claimed that this effect results in an incorrect HHG cutoff energy. We reproduced their main results, but found that the unphysical even harmonics that they observed originated from numerical errors introduced by the boundary conditions. We show that contrary to their claims, the HHG cutoff energy calculated within TDDFT agrees perfectly with the standard and well-established models of HHG.

Optimal control theory, also known as Pontryagin's Maximum Principle, is applied to the quantum parameter estimation in the presence of decoherence. An efficient procedure is devised to compute the gradient of quantum Fisher information with respect to the control parameters and is used to construct the optimal control protocol. The proposed procedure keeps the control problem in the time-invariant form so that both first-order and second-order optimality conditions derived from Pontryagin's Maximum Principle apply; the second-order condition turns out to be crucial when the optimal control contains singular arcs. Concretely we look for the optimal control that maximizes quantum Fisher information for "twist and turn" problem. We find that the optimal control is singular without dissipation but can become unbounded once the quantum decoherence is introduced. An amplitude constraint is needed to guarantee a bounded solution. With quantum decoherence, the maximum quantum Fisher information happens at a finite time due to the decoherence, and the asymptotic value depends on the specific decoherence channel and the control of consideration.

We adapt recent tools developed for the analysis of Stochastic Gradient Descent (SGD) in non-convex optimization to obtain convergence and sample complexity guarantees for the vanilla policy gradient (PG). Our only assumptions are that the expected return is smooth w.r.t. the policy parameters, that its H-step truncated gradient is close to the exact gradient, and a certain ABC assumption. This assumption requires the second moment of the estimated gradient to be bounded by A ≥ 0 times the suboptimality gap, B ≥ 0 times the norm of the full batch gradient and an additive constant C ≥ 0, or any combination of aforementioned. We show that the ABC assumption is more general than the commonly used assumptions on the policy space to prove convergence to a stationary point. We provide a single convergence theorem that recovers the O(−4) sample complexity of PG. Our results also affords greater f lexibility in the choice of hyper parameters such as the step size and places no restriction on the batch size m, including the single trajectory case (i.e., m = 1). We then instantiate our theorem in different settings, where we both recover existing results and obtained improved sample complexity, e.g., for convergence to the global optimum for Fisher-nondegenerated parameterized policies.

We present a principled approach for designing stochastic Newton methods for solving f inite sum optimization problems. Our approach has two steps. First, we re-write the stationarity conditions as a system of nonlinear equations that associates each data point to a new row. Second, we apply a Subsampled Newton Raphson method to solve this system of nonlinear equations. Using our approach, we develop a new Stochastic Average Newton (SAN) method, which is incremental by design, in that it requires only a single data point per iteration. It is also cheap to implement when solving regularized generalized linear models, with a cost per iteration of the order of the number of the parameters. We show through numerical experiments that SAN requires no knowledge about the problem, neither parameter tuning, while remaining competitive as compared to classical variance reduced gradient methods (e.g. SAG and SVRG), incremental Newton and quasiNewton methods (e.g. SNM, IQN).

Signatures of vertical disequilibrium have been observed across the Milky Way's (MW's) disk. These signatures manifest locally as unmixed phase spirals in z–vz space ("snails-in-phase"), and globally as nonzero mean z and vz, wrapping around the disk into physical spirals in the x–y plane ("snails-in-space"). We explore the connection between these local and global spirals through the example of a satellite perturbing a test-particle MW-like disk. We anticipate our results to broadly apply to any vertical perturbation. Using a z–vz asymmetry metric, we demonstrate that in test-particle simulations: (a) multiple local phase-spiral morphologies appear when stars are binned by azimuthal action Jϕ, excited by a single event (in our case, a satellite disk crossing); (b) these distinct phase spirals are traced back to distinct disk locations; and (c) they are excited at distinct times. Thus, local phase spirals offer a global view of the MW's perturbation history from multiple perspectives. Using a toy model for a Sagittarius (Sgr)–like satellite crossing the disk, we show that the full interaction takes place on timescales comparable to orbital periods of disk stars within R ≲ 10 kpc. Hence such perturbations have widespread influence, which peaks in distinct regions of the disk at different times. This leads us to examine the ongoing MW–Sgr interaction. While Sgr has not yet crossed the disk (currently, zSgr ≈ −6 kpc, vz,Sgr ≈ 210 km s−1), we demonstrate that the peak of the impact has already passed. Sgr's pull over the past 150 Myr creates a global vz signature with amplitude ∝ MSgr, which might be detectable in future spectroscopic surveys.

We present the results from a new search for candidate galaxies at z ~ 8.5-11 discovered over the 850 arcmin^2 area probed by the Cosmic Assembly Near-Infrared Deep Extragalactic Legacy Survey (CANDELS). We use a photometric redshift selection including both Hubble and Spitzer Space Telescope photometry to robustly identify galaxies in this epoch at F160W 8. We calculate that the presence of seven galaxies in a single field (EGS) is an outlier at the 2-sigma significance level, implying the discovery of a significant overdensity. These scenarios will be imminently testable to high confidence within the first year of observations of the James Webb Space Telescope.

We demonstrate the utility of the bispectrum, the Fourier three-point correlation function, for studying driving scales of magnetohydrodynamic (MHD) turbulence in the interstellar medium. We calculate the bispectrum by implementing a parallelized Monte Carlo direct measurement method, which we have made publicly available. In previous works, the bispectrum has been used to identify non-linear scaling correlations and break degeneracies in lower-order statistics like the power spectrum. We find that the bicoherence, a related statistic which measures phase coupling of Fourier modes, identifies turbulence driving scales using density and column density fields. In particular, it shows that the driving scale is phase-coupled to scales present in the turbulent cascade. We also find that the presence of an ordered magnetic field at large-scales enhances phase coupling as compared to a pure hydrodynamic case. We, therefore, suggest the bispectrum and bicoherence as tools for searching for non-locality for wave interactions in MHD turbulence.