Publications

The Vera C. Rubin Observatory Legacy Survey of Space and Time (LSST) will observe several Deep Drilling Fields (DDFs) to a greater depth and with a more rapid cadence than the main survey. In this paper, we describe the ``DeepDrill'' survey, which used the Spitzer Space Telescope Infrared Array Camera (IRAC) to observe three of the four currently defined DDFs in two bands, centered on 3.6 μm and 4.5 μm. These observations expand the area which was covered by an earlier set of observations in these three fields by the Spitzer Extragalactic Representative Volume Survey (SERVS). The combined DeepDrill and SERVS data cover the footprints of the LSST DDFs in the Extended Chandra Deep Field-South field (ECDFS), the ELAIS-S1 field (ES1), and the XMM Large-Scale Structure Survey field (XMM-LSS). The observations reach an approximate 5σ point-source depth of 2 μJy (corresponding to an AB magnitude of 23.1; sufficient to detect a 1011M⊙ galaxy out to z≈5) in each of the two bands over a total area of ≈29deg2. The dual-band catalogues contain a total of 2.35 million sources. In this paper we describe the observations and data products from the survey, and an overview of the properties of galaxies in the survey. We compare the source counts to predictions from the SHARK semi-analytic model of galaxy formation. We also identify a population of sources with extremely red ([3.6]−[4.5] >1.2) colours which we show mostly consists of highly-obscured active galactic nuclei.

The back propagation algorithm is an invaluable tool for training artificial neural networks; however, because of a weight sharing requirement, it does not provide a plausible model of brain function. Here, in the context of a two-layer network, we derive an algorithm for training a neural network which avoids this problem by not requiring explicit error computation and back propagation. Furthermore, our algorithm maps onto a neural network that bears a remarkable resemblance to the connectivity structure and learning rules of the cortex. We find that our algorithm empirically performs comparably to backprop on a number of datasets.

Chromodomain helicase DNA-binding 8 (CHD8) is one of the most frequently mutated genes causative of autism spectrum disorder (ASD). While its phenotypic spectrum often encompasses macrocephaly and hence implicates cortical abnormalities in this form of ASD, the neurodevelopmental impact of human CHD8 haploinsufficiency remains unexplored. Here we combined human cerebral organoids and single cell transcriptomics to define the effect of ASD-linked CHD8 mutations on human cortical development. We found that CHD8 haploinsufficiency causes a major disruption of neurodevelopmental trajectories with an accelerated generation of inhibitory neurons and a delayed production of excitatory neurons alongside the ensuing protraction of the proliferation phase. This imbalance leads to a significant enlargement of cerebral organoids aligned to the macrocephaly observed in patients with CHD8 mutations. By adopting an isogenic design of patient-specific mutations and mosaic cerebral organoids, we define genotype-phenotype relationships and uncover their cell-autonomous nature. Finally, our results assign different CHD8-dependent molecular defects to particular cell types, pointing to an abnormal and extended program of proliferation and alternative splicing specifically affected in, respectively, the radial glial and immature neuronal compartments. By identifying temporally restricted cell-type specific effects of human CHD8 mutations, our study uncovers developmental alterations as reproducible endophenotypes for neurodevelopmental disease modelling.

K2 observations of the weak-lined T Tauri binary V928 Tau A+B show the detection of a single, asymmetric eclipse which may be due to a previously unknown substellar companion eclipsing one component of the binary with an orbital period > 66 days. Over an interval of about 9 hours, one component of the binary dims by around 60%, returning to its normal brightness about 5 hours later. From modeling of the eclipse shape we find evidence that the eclipsing companion may be surrounded by a disk or a vast ring system. The modeled disk has a radius of 0.9923±0.0005R∗, with an inclination of 56.78±0.03∘, a tilt of 41.22±0.05∘, an impact parameter of −0.2506±0.0002R∗ and an opacity of 1.00. The occulting disk must also move at a transverse velocity of 6.637±0.002R∗day−1, which depending on whether it orbits V928 Tau A or B, corresponds to approximately 73.53 or 69.26 kms−1. A search in ground based archival data reveals additional dimming events, some of which suggest periodicity, but no unambiguous period associated with the eclipse observed by K2. We present a new epoch of astrometry which is used to further refine the orbit of the binary, presenting a new lower bound of 67 years, and constraints on the possible orbital periods of the eclipsing companion. The binary is also separated by 18" (∼2250 au) from the lower mass CFHT-BD-Tau 7, which is likely associated with V928 Tau A+B. We also present new high dispersion optical spectroscopy that we use to characterize the unresolved stellar binary.

Dental caries, the most common chronic infectious disease worldwide, has a complex etiology involving the interplay of microbial and host factors that are not completely understood. In this study, the oral microbiome and 38 host cytokines and chemokines were analyzed across 23 children with caries and 24 children with healthy dentition. De novo assembly of metagenomic sequencing obtained 527 metagenome-assembled genomes (MAGs), representing 150 bacterial species. Forty-two of these species had no genomes in public repositories, thereby representing novel taxa. These new genomes greatly expanded the known pangenomes of many oral clades, including the enigmatic Saccharibacteria clades G3 and G6, which had distinct functional repertoires compared to other oral Saccharibacteria. Saccharibacteria are understood to be obligate epibionts, which are dependent on host bacteria. These data suggest that the various Saccharibacteria clades may rely on their hosts for highly distinct metabolic requirements, which would have significant evolutionary and ecological implications. Across the study group, Rothia, Neisseria, and Haemophilus spp. were associated with good dental health, whereas Prevotella spp., Streptococcus mutans, and Human herpesvirus 4 (Epstein-Barr virus [EBV]) were more prevalent in children with caries. Finally, 10 of the host immunological markers were significantly elevated in the caries group, and co-occurrence analysis provided an atlas of potential relationships between microbes and host immunological molecules. Overall, this study illustrated the oral microbiome at an unprecedented resolution and contributed several leads for further study that will increase the understanding of caries pathogenesis and guide therapeutic development.

The recent detection of GW190521 stimulated ideas on how to populate the predicted black hole (BH) pair-instability (PI) mass gap. One proposal is the dynamical merger of two stars below the PI regime forming a star with a small core and an oversized envelope. We outline the main challenges this scenario faces to form one BH in the gap. In particular, the core needs to avoid growing during the merger, and the merger product needs to retain enough mass, including in the subsequent evolution, and at core collapse (CC). We explore this scenario with detailed stellar evolution calculations, starting with ad hoc initial conditions enforcing no core growth during the merger. We find that these massive merger products are likely to be helium-rich and spend most of their remaining lifetime within regions of instabilities in the Herzsprung–Russell diagram, such as luminous blue variable eruptions. An energetic estimate of the amount of mass loss neglecting the back reaction of the star suggests that the total amount of mass that can be removed at low metallicity is ≲1 M⊙. This is small enough that at CC our models are retaining sufficient mass to form BHs in the PI gap similar to the recent ones detected by LIGO/Virgo. However, mass loss at the time of merger, the resulting core structure, and the mass loss at CC still need to be quantified for these models to confirm the viability of this scenario.

An identification is found between meta-learning and the problem of determining the ground state of a randomly generated Hamiltonian drawn from a known ensemble. A model-agnostic meta-learning approach is proposed to solve the associated learning problem and a preliminary experimental study of random Max-Cut problems indicates that the resulting Meta Variational Monte Carlo accelerates training and improves convergence.

In cells, cytoskeletal filament networks are responsible for cell movement, growth, and division. Filaments in the cytoskeleton are driven and organized by crosslinking molecular motors. In reconstituted cytoskeletal systems, motor activity is responsible for far-fromequilibrium phenomena such as active stress, self-organized flow, and spontaneous nematic defect generation. How microscopic interactions between motors and filaments lead to larger-scale dynamics remains incompletely understood. To build from motor-filament interactions to predict bulk behavior of cytoskeletal systems, more computationally efficient techniques for modeling motor-filament interactions are needed. Here we derive a coarsegraining hierarchy of explicit and continuum models for crosslinking motors that bind to and walk on filament pairs. We compare the steady-state motor distribution and motorinduced filament motion for the different models and analyze their computational cost. All three models agree well in the limit of fast motor binding kinetics. Evolving a truncated moment expansion of motor density speeds the computation by 103–106
compared to the explicit or continuous-density simulations, suggesting an approach for more efficient simulation of large networks. These tools facilitate further study of motor-filament networks on micrometer to millimeter length scales.

BACKGROUND
The efficacy of public health measures to control the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not been well studied in young adults.

METHODS
We investigated SARS-CoV-2 infections among U.S. Marine Corps recruits who underwent a 2-week quarantine at home followed by a second supervised 2-week quarantine at a closed college campus that involved mask wearing, social distancing, and daily temperature and symptom monitoring. Study volunteers were tested for SARS-CoV-2 by means of quantitative polymerase-chain-reaction (qPCR) assay of nares swab specimens obtained between the time of arrival and the second day of supervised quarantine and on days 7 and 14. Recruits who did not volunteer for the study underwent qPCR testing only on day 14, at the end of the quarantine period. We performed phylogenetic analysis of viral genomes obtained from infected study volunteers to identify clusters and to assess the epidemiologic features of infections.

RESULTS
A total of 1848 recruits volunteered to participate in the study; within 2 days after arrival on campus, 16 (0.9%) tested positive for SARS-CoV-2, 15 of whom were asymptomatic. An additional 35 participants (1.9%) tested positive on day 7 or on day 14. Five of the 51 participants (9.8%) who tested positive at any time had symptoms in the week before a positive qPCR test. Of the recruits who declined to participate in the study, 26 (1.7%) of the 1554 recruits with available qPCR results tested positive on day 14. No SARS-CoV-2 infections were identified through clinical qPCR testing performed as a result of daily symptom monitoring. Analysis of 36 SARS-CoV-2 genomes obtained from 32 participants revealed six transmission clusters among 18 participants. Epidemiologic analysis supported multiple local transmission events, including transmission between roommates and among recruits within the same platoon.

CONCLUSIONS
Among Marine Corps recruits, approximately 2% who had previously had negative results for SARS-CoV-2 at the beginning of supervised quarantine, and less than 2% of recruits with unknown previous status, tested positive by day 14. Most recruits who tested positive were asymptomatic, and no infections were detected through daily symptom monitoring. Transmission clusters occurred within platoons. (Funded by the Defense Health Agency and others.)

In lung cancer, enrichment of the lower airway microbiota with oral commensals commonly occurs and ex vivo models support that some of these bacteria can trigger host transcriptomic signatures associated with carcinogenesis. Here, we show that this lower airway dysbiotic signature was more prevalent in group IIIB-IV TNM stage lung cancer and is associated with poor prognosis, as shown by decreased survival among subjects with early stage disease (I-IIIA) and worse tumor progression as measured by RECIST scores among subjects with IIIB-IV stage disease. In addition, this lower airway microbiota signature was associated with upregulation of IL-17, PI3K, MAPK and ERK pathways in airway transcriptome, and we identified Veillonella parvula as the most abundant taxon driving this association. In a KP lung cancer model, lower airway dysbiosis with V. parvula led to decreased survival, increased tumor burden, IL-17 inflammatory phenotype and activation of checkpoint inhibitor markers.