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Understanding and eliminating spurious modes in variational Monte Carlo using collective variables
The use of neural network parametrizations to represent the ground state in variational Monte Carlo (VMC) calculations has generated intense interest in recent years. However, as we demonstrate in the context of the periodic Heisenberg spin chain, this approach can produce unreliable wave function approximations. One of the most obvious signs of failure is the occurrence of random, persistent spikes in the energy estimate during training. These energy spikes are caused by regions of configuration space that are over-represented by the wave function density, which are called “spurious modes” in the machine learning literature. After exploring these spurious modes in detail, we demonstrate that a collective-variable-based penalization yields a substantially more robust training procedure, preventing the formation of spurious modes and improving the accuracy of energy estimates. Because the penalization scheme is cheap to implement and is not specific to the particular model studied here, it can be extended to other applications of VMC where a reasonable choice of collective variable is available
Seismological Stress Drops for Confined Ruptures Are Invariant to Normal Stress
Seismic moment and rupture length can be combined to infer stress drop, a key parameter for assessing earthquakes. In natural earthquakes, stress drops are largely depth-independent, which is surprising given the expected dependence of frictional stress on normal stresses and hence overburden. We have developed a transparent experimental fault that allows direct observation of thousands of slip events, with ruptures that are fully contained within the fault. Surprisingly, the observed stress drops are largely independent of both the magnitude of normal stress and its heterogeneity, capturing the independence seen in nature. However, we observe larger, normal stress-dependent stress drops when the fault area is reduced, which allows slip events to frequently reach the edge of the interface. We conclude that confined ruptures have normal stress independent stress drops, and thus the depth-independent stress drops of tectonic earthquakes may be a consequence of their confined nature
Complex organosulfur molecules on comet 67P: Evidence from the ROSINA measurements and insights from laboratory simulations
The ROSINA (Rosetta Orbiter Spectrometer for Ion and Neutral Analysis) instrument aboard the Rosetta mission revolutionized our understanding of cometary material composition. One of Rosetta’s key findings is the complexity of the composition of comet 67P/Churyumov-Gerasimenko. Here, we used ROSINA data to analyze dust particles that were volatilized during a dust event in September 2016 and report the detection of large organosulfur species and an increase in the abundances of sulfurous species previously detected in the coma. Our data support the presence of complex sulfur-bearing organics on the surface of the comet. In addition, we conducted laboratory simulations that show that this material may have formed from chemical reactions that were initiated by the irradiation of mixed ices containing H2S. Our findings highlight the importance of sulfur chemistry in cometary and precometary materials and the possibility of characterizing organosulfur materials in other comets and small icy bodies using the James Webb Space Telescope
A model of the post-implantation human embryo derived from pluripotent stem cells
The human embryo undergoes morphogenetic transformations following implantation into the uterus, yet our knowledge of this crucial stage is limited by the inability to observe the embryo in vivo. Stem cell-derived models of the embryo are important tools to interrogate developmental events and tissue-tissue crosstalk during these stages. Here, we establish a model of the human post-implantation embryo, a human embryoid, comprised of embryonic and extraembryonic tissues. We combine two types of extraembryonic-like cells generated by transcription factor overexpression with wildtype embryonic stem cells and promote their self-organization into structures that mimic several aspects of the post-implantation human embryo. These self-organized aggregates contain a pluripotent epiblast-like domain surrounded by extraembryonic-like tissues. Our functional studies demonstrate that the epiblast-like domain robustly differentiates to amnion, extraembryonic mesenchyme, and primordial germ cell-like cells in response to BMP cues. In addition, we identify an inhibitory role for SOX17 in the specification of anterior hypoblast-like cells. Modulation of the subpopulations in the hypoblast-like compartment demonstrated that extraembryonic-like cells impact epiblast-like domain differentiation, highlighting functional tissue-tissue crosstalk. In conclusion, we present a modular, tractable, integrated model of the human embryo that will allow us to probe key questions of human post-implantation development, a critical window when significant numbers of pregnancies fail
Direct androgen receptor regulation of sexually dimorphic gene expression in the mammalian kidney
Mammalian organs exhibit distinct physiology, disease susceptibility and injury responses between the sexes. In the mouse kidney, sexually dimorphic gene activity maps predominantly to proximal tubule (PT) segments. Bulk RNA-seq data demonstrated sex differences were established from 4 and 8 weeks after birth under gonadal control. Hormone injection studies and genetic removal of androgen and estrogen receptors demonstrated androgen receptor (AR) mediated regulation of gene activity in PT cells as the regulatory mechanism. Interestingly, caloric restriction feminizes the male kidney. Single-nuclear multiomic analysis identified putative cis-regulatory regions and cooperating factors mediating PT responses to AR activity in the mouse kidney. In the human kidney, a limited set of genes showed conserved sex-linked regulation while analysis of the mouse liver underscored organ-specific differences in the regulation of sexually dimorphic gene expression. These findings raise interesting questions on the evolution, physiological significance, and disease and metabolic linkage, of sexually dimorphic gene activity
Structure of Anabaena flos-aquae gas vesicles revealed by cryo-ET
Gas vesicles (GVs) are gas-filled protein nanostructures employed by several species of bacteria and archaea as flotation devices to enable access to optimal light and nutrients. The unique physical properties of GVs have led to their use as genetically encodable contrast agents for ultrasound and MRI. Currently, however, the structure and assembly mechanism of GVs remain unknown. Here we employ cryoelectron tomography to reveal how the GV shell is formed by a helical filament of highly conserved GvpA subunits. This filament changes polarity at the center of the GV cylinder, a site that may act as an elongation center. Subtomogram averaging reveals a corrugated pattern of the shell arising from polymerization of GvpA into a β sheet. The accessory protein GvpC forms a helical cage around the GvpA shell, providing structural reinforcement. Together, our results help explain the remarkable mechanical properties of GVs and their ability to adopt different diameters and shapes
Being Black in biophysics
Building off the momentum of the Black Lives Matter movement and serving as a platform for radical reform of structural inequities, the Biophysical Society (BPS) held the President’s 2023 Black in Biophysics Symposium. The goal of this symposium was to bring to light the remarkable work of some of our Black BPS colleagues flanked by two very different cultural perspectives explaining why, in these modern times, such a spotlight is still needed. In his introduction, Bil Clemons provided data to underscore the persistent legacy of slavery, and Theanne Griffith closed the event with a moving personal testimony. BPS has long served as a platform for social change, most successfully in its effort to promote participation by women and international scientists. These were intentional acts, and the resulting positive changes are sustained only by constant vigilance. Let us apply the same intention, the same vigilance, to fostering diversity, equity, inclusion, and retention within our ranks and providing critical role models for trainees of all walks of life. Let us start seeing Black in biophysics, with the generous help of Bil and Theanne in their own words
The Low-temperature Corona in ESO 511−G030 Revealed by NuSTAR and XMM-Newton
We present the results from a coordinated XMM-Newton + NuSTAR observation of the Seyfert 1 galaxy ESO 511−G030. With this joint monitoring program, we conduct a detailed variability and spectral analysis. The source remained in a low flux and very stable state throughout the observation period, although there are slight fluctuations of flux over long timescales. The broadband (0.3–78 keV) spectrum shows the presence of a power-law continuum with a soft excess below 2 keV, a relatively narrow iron Kα emission (∼6.4 keV), and an obvious cutoff at high energies. We find that the soft excess can be modeled by two different possible scenarios: a warm (kTₑ_e ∼ 0.19 keV) and optically thick (τ = 18–25) Comptonizing corona or a relativistic reflection from a high-density (log[nₑ/cm⁻³] = 17.1 – 18.5) inner disk. All models require a low temperature (kT_e ∼ 13 keV) for the hot corona
CHIME/FRB Discovery of 25 Repeating Fast Radio Burst Sources
We present the discovery of 25 new repeating fast radio burst (FRB) sources found among CHIME/FRB events detected between 2019 September 30 and 2021 May 1. The sources were found using a new clustering algorithm that looks for multiple events colocated on the sky having similar dispersion measures (DMs). The new repeaters have DMs ranging from ∼220 to ∼1700 pc cm⁻³, and include sources having exhibited as few as two bursts to as many as twelve. We report a statistically significant difference in both the DM and extragalactic DM (eDM) distributions between repeating and apparently nonrepeating sources, with repeaters having a lower mean DM and eDM, and we discuss the implications. We find no clear bimodality between the repetition rates of repeaters and upper limits on repetition from apparently nonrepeating sources after correcting for sensitivity and exposure effects, although some active repeating sources stand out as anomalous. We measure the repeater fraction over time and find that it tends to an equilibrium of 2.6^(+2.9)_(-2.6)% over our total time-on-sky thus far. We also report on 14 more sources, which are promising repeating FRB candidates and which merit follow-up observations for confirmation
Isomorphisms of 4D N = 2 SCFTs from 6D
There exist 4D N = 2 superconformal field theories (SCFTs) in class S that have different constructions as punctured Riemann surfaces, but which nevertheless appear to describe the same physics. Some of these class S theories have an alternative construction as torus-compactifications of 6D (1, 0) SCFTs. We demonstrate that the 6D SCFTs are isomorphic. Each 6D SCFT in question can be obtained from a parent 6D SCFT by Higgs branch renormalization group flow, and the parent theory possesses a discrete symmetry under which the relevant Higgs branch flows are exchanged. The existence of this discrete symmetry, which may be embedded in an enhanced continuous symmetry, proves that the original pair of class S theories are, in fact, isomorphic