bluuebunny/crossref_metadata_2025 huggingface dataset:
Using in situ solar-wind observations to generate inner-boundary conditions to outer-heliosphere simulations – I. Dynamic time warping applied to synthetic observations
Authors: Owens Mathew J , Nichols Jonathan D
Published: September 2021

The structure and dynamics of the magnetospheres of the outer planets, particularly Saturn and Jupiter, have been explored through both remote and in situ observations. Interpreting these observations often necessitates simultaneous knowledge of the solar-wind conditions impinging on the magnetosphere. Without an available upstream monitor, solar-wind context is typically provided using models initiated with either the output of magnetogram-constrained coronal models or, more commonly, in situ observations from 1 au. While 1-au observations provide a direct measure of solar-wind conditions, they are single-point observations and thus require interpolation to provide inputs to outer-heliosphere solar-wind models. In this study, we test the different interpolation methods using synthetic 1-au observations of time-evolving solar-wind structure. The simplest method is ‘corotation’, which assumes solar-wind structure is a steady state and rotates with the Sun. This method of reconstruction produces discontinuities in the solar-wind inputs as new observations become available. This can be reduced by corotating both backwards and forwards in time, but this still introduces large errors in the magnitude and timing of solar-wind streams. We show how the dynamic time warping (DTW) algorithm can provide around an order-of-magnitude improvement in solar-wind inputs to the outer-heliosphere model from in situ observations near 1 au. This is intended to build the foundation for further work demonstrating and validating methods to improve inner-boundary conditions of outer-heliosphere solar-wind models, including dealing with solar-wind transients and quantifying the improvements at Saturn and Jupiter.
GRMHD simulations of BH activation by small scale magnetic loops: formation of striped jets and active coronae
Authors: Chashkina Anna , Bromberg Omer , Levinson Amir
Published: September 2021

We have performed a series of numerical experiments aimed at studying the activation of Kerr black holes (BHs) by advection of small scale magnetic fields. Such configurations may potentially give rise to the formation of quasi-striped Blandford-Znajek jets. It can also lead to enhanced dissipation and generation of plasmoids in current sheets formed in the vicinity of the BH horizon, which may constitute a mechanism to power the hard X-ray emission seen in many accreting BH systems (a la lamppost models). Our analysis suggests that formation of quasi-striped jets with significant power may be possible provided loops with alternating polarity having sizes larger than ∼10rg or so can be maintained (either form sporadically or advected from outside) at a radius ≲ 102rg. This conclusion is consistent with recent results of general relativistic force-free simulations. We also find that the accretion dynamics exhibits cyclic behaviour in Magnetically Arrested Disc states, alternating between high accretion phases and quenched accretion phases during which the magnetosphere becomes force-free out to radii ≳ 10rg. We suggest that such a behaviour should lead to notable variations of the observed luminosity and image of the inner disc (BH shadow image). Finally, we find that the transition between accreted loops on the BH gives rise to the formation of current sheets and energetic plasmoids on the jet boundary during intermittent periods when the jet becomes inactive, in addition to an equatorial current sheet that forms during peaks in the jet activity.
On the initial mass–radius relation of stellar clusters
Authors: Choksi Nick , Kruijssen J M Diederik
Published: September 2021

Young stellar clusters across nearly five orders of magnitude in mass appear to follow a power-law mass–radius relationship (MRR), $R_{\star }\propto M_{\star }^{\alpha }$, with α ≈ 0.2–0.33. We develop a simple analytic model for the cluster mass–radius relation. We consider a galaxy disc in hydrostatic equilibrium, which hosts a population of molecular clouds that fragment into clumps undergoing cluster formation and feedback-driven expansion. The model predicts a mass–radius relation of $R_{\star }\propto M_{\star }^{1/2}$ and a dependence on the kpc-scale gas surface density $R_{\star }\propto \Sigma _{\rm g}^{-1/2}$, which results from the formation of more compact clouds (and cluster-forming clumps within) at higher gas surface densities. This environmental dependence implies that the high-pressure environments in which the most massive clusters can form also induce the formation of clusters with the smallest radii, thereby shallowing the observed MRR at high-masses towards the observed $R_{\star }\propto M_{\star }^{1/3}$. At low cluster masses, relaxation-driven expansion induces a similar shallowing of the MRR. We combine our predicted MRR with a simple population synthesis model and apply it to a variety of star-forming environments, finding good agreement. Our model predicts that the high-pressure formation environments of globular clusters at high redshift naturally led to the formation of clusters that are considerably more compact than those in the local Universe, thereby increasing their resilience to tidal shock-driven disruption and contributing to their survival until the present day.
Parameters of the X-ray binary system Scorpius X-1
Authors: Cherepashchuk A M , Khruzina T S , Bogomazov A I
Published: September 2021

We modelled optical light curves of Sco X-1 obtained by the Kepler Space Telescope during the K2 mission. Modelling was performed for the case of strong heating of the optical star and accretion disc by X-rays. In the model considered, the optical star fully filled its Roche lobe. We investigated the inverse problem in wide ranges of values of model parameters and estimated the following parameters of Sco X-1: the mass ratio of components q = Mx/Mv = 3.6 (3.5–3.8), where Mx and Mv are the masses of the neutron and optical stars correspondingly; the orbital inclination was i = 30° (25–34°). In the brackets the uncertainties of parameters q and i are shown; these originated due to uncertainties of characteristics of the physical model of Sco X-1. The temperature of the non-heated optical star was T2 = 2500–3050 K, its radius was R2 = 1.25R⊙ = 8.7 × 1010 cm, and its bolometric luminosity was Lbol = (2.1–4.6) × 1032 erg s−1. The mass of the star was $M_v\simeq 0.4\, \mathrm{M}_{\odot }$. The contribution of the X-ray-heated accretion disc dominated in the total optical emission of Sco X-1. The transition between low and high states occurred due to the increase of X-ray luminosity by a factor of 2–3.
Global 3D radiation hydrodynamic simulations of proto-Jupiter’s convective envelope
Authors: Zhu Zhaohuan , Jiang Yan-Fei , Baehr Hans , Youdin Andrew N , Armitage Philip J , Martin Rebecca G
Published: September 2021

The core accretion model of giant planet formation has been challenged by the discovery of recycling flows between the planetary envelope and the disc that can slow or stall envelope accretion. We carry out 3D radiation hydrodynamic simulations with an updated opacity compilation to model the proto-Jupiter’s envelope. To isolate the 3D effects of convection and recycling, we simulate both isolated spherical envelopes and envelopes embedded in discs. The envelopes are heated at given rates to achieve steady states, enabling comparisons with 1D models. We vary envelope properties to obtain both radiative and convective solutions. Using a passive scalar, we observe significant mass recycling on the orbital time-scale. For a radiative envelope, recycling can only penetrate from the disc surface until ∼0.1–0.2 planetary Hill radii, while for a convective envelope, the convective motion can ‘dredge up’ the deeper part of the envelope so that the entire convective envelope is recycled efficiently. This recycling, however, has only limited effects on the envelopes’ thermal structure. The radiative envelope embedded in the disc has identical structure as the isolated envelope. The convective envelope has a slightly higher density when it is embedded in the disc. We introduce a modified 1D approach which can fully reproduce our 3D simulations. With our updated opacity and 1D model, we recompute Jupiter’s envelope accretion with a 10 M⊕ core, and the time-scale to runaway accretion is shorter than the disc lifetime as in prior studies. Finally, we discuss the implications of the efficient recycling on the observed chemical abundances of the planetary atmosphere (especially for super-Earths and mini-Neptunes).
State transitions of GX 339-4 during its outburst rising phase
Authors: Shui Q C , Yin H X , Zhang S , Qu J L , Chen Y P , Kong L D , Wang P J , Zhang H F , Song J X , Ning B , Wang Y F , Chang Z , Zhang P
Published: September 2021

We investigate systematically four outbursts of black hole system GX 339-4 observed by the Rossi X-ray Timing Explorer (RXTE) in both spectral and timing domains and find that these outbursts have some common properties, although they experience different ‘q’ tracks in the hardness–intensity diagram (HID). While the spectral indices are around 1.5 in the low/hard state (LHS) and 2.4 in the soft intermediate state (SIMS) and high/soft state (HSS), the spectral parameters of thermal, non-thermal, and reflection components vary significantly in transitions from the LHS to HIMS. Also, the quasi-periodic oscillation (QPO) shows a peculiar behaviour during the state transition between the LHS and HIMS: the RMS drop of the type C fundamental QPO is accompanied by the appearance of the second harmonic. Interestingly, the QPO RMS is found to have a similar linear relationship with the non-thermal fraction of emission in different outbursts. These findings provide more clues to aid our understanding of the outbursts of a black hole X-ray binary system.
Morphology of solar system scale plasma lenses in the interstellar medium: a test from pulsar scintillation parabolic arcs
Authors: Shi Xun
Published: September 2021

Scintillation spectra of some pulsars have suggested the existence of ≲ AU scale density structures in the ionized interstellar medium, whose astrophysical correspondence is still a mystery. The detailed study of Brisken et al. suggested two possible morphologies for these structures: A parallel set of filaments or sheets (the ‘parallel stripes model’), or a filament broken up into denser knots (the ‘threaded beads model’). Here, we propose a straightforward test that can distinguish these two morphologies: Whether the apex of the main parabolic arc created by the scattered images deviates from the origin of the scintillation spectrum or not. In the ‘parallel stripes’ model, the scattered images move along the stripes as the relative position of the pulsar moves. As a result, the pulsar is always co-linear with the scattered images, and thus, the apex of the main parabolic arc stays at the origin of the scintillation spectrum. In the ‘threaded beads’ model, the scattered images remain at almost fixed positions relative to the density structures, and thus, the pulsar is not co-linear with the scattered images at most times, leading to an offset between the apex and the origin. Looking for this possible offset in a large sample of pulsar scintillation spectra, or monitoring the evolution of parabolic arcs will help pin down the morphology of these tiny density structures and constrain their astrophysical origin.
Exploring the possibility of Peter Pan discs across stellar mass
Authors: Wilhelm Martijn J C , Portegies Zwart Simon
Published: September 2021

Recently, several accreting M dwarf stars have been discovered with ages far exceeding the typical protoplanetary disc lifetime. These ‘Peter Pan discs’ can be explained as primordial discs that evolve in a low-radiation environment. The persistently low masses of the host stars raise the question whether primordial discs can survive up to these ages around stars of higher mass. In this work we explore the way in which different mass loss processes in protoplanetary discs limit their maximum lifetimes, and how this depends on host star mass. We find that stars with masses ≲0.6 M⊙ can retain primordial discs for ∼50 Myr. At stellar masses ≳0.8 M⊙, the maximum disc lifetime decreases strongly to below 50 Myr due to relatively more efficient accretion and photoevaporation by the host star. Lifetimes up to 15 Myr are still possible for all host star masses up to ∼2 M⊙. For host star masses between 0.6 and 0.8 M⊙, accretion ceases and an inner gap forms before 50 Myr in our models. Observations suggest that such a configuration is rapidly dispersed. We conclude that Peter Pan discs can only occur around M dwarf stars.
Surface manifestation of stochastically excited internal gravity waves
Authors: Lecoanet Daniel , Cantiello Matteo , Anders Evan H , Quataert Eliot , Couston Louis-Alexandre , Bouffard Mathieu , Favier Benjamin , Le Bars Michael
Published: September 2021

Recent photometric observations of massive stars show ubiquitous low-frequency ‘red noise’ variability, which has been interpreted as internal gravity waves (IGWs). Simulations of IGWs generated by convection show smooth surface wave spectra, qualitatively matching the observed red noise. Theoretical calculations using linear wave theory by Shiode et al. and Lecoanet et al. predict IGWs should manifest at the surface as regularly spaced peaks associated with standing g modes. In light of the apparent discrepancy between these theories and simulations/observations, we test the theories with simplified 2D numerical simulations of wave generation by convection. The simulations agree with the transfer function calculations presented in Lecoanet et al., demonstrating that the transfer function correctly models linear wave propagation. However, there are differences between our simulations and the g-mode amplitude predictions of Shiode et al. This is because that work did not take into account the finite width of the g-mode peaks; after correcting for this finite width, we again find good agreement between theory and simulations. This paper verifies the theoretical approach of Lecoanet et al. and strengthens their conclusion that IGWs generated by core convection do not have a surface manifestation consistent with observed low-frequency variability of massive stars.
Fragmentation of ring galaxies and transformation to clumpy galaxies
Authors: Inoue Shigeki , Yoshida Naoki , Hernquist Lars
Published: September 2021

We study the fragmentation of collisional ring galaxies (CRGs) using a linear perturbation analysis that computes the physical conditions of gravitational instability, as determined by the balance of self-gravity of the ring against pressure and Coriolis forces. We adopt our formalism to simulations of CRGs and show that the analysis can accurately characterize the stability and onset of fragmentation, although the linear theory appears to underpredict the number of fragments of an unstable CRG by a factor of 2. In addition, since the orthodox ‘density-wave’ model is inapplicable to such self-gravitating rings, we devise a simple approach that describes the rings propagating as material waves. We find that the toy model can predict whether the simulated CRGs fragment or not using information from their pre-collision states. We also apply our instability analysis to a CRG discovered at a high redshift, z = 2.19. We find that a quite high-velocity dispersion is required for the stability of the ring, and therefore the CRG should be unstable to ring fragmentation. CRGs are rarely observed at high redshifts, and this may be because CRGs are usually too faint. Since the fragmentation can induce active star formation and make the ring bright enough to observe, the instability could explain this rarity. An unstable CRG fragments into massive clumps retaining the initial disc rotation, and thus it would evolve into a clumpy galaxy with a low surface density in an interclump region.
Profile changes associated with dispersion measure events in PSR J1713+0747
Authors: Lin Fang Xi , Lin Hsiu-Hsien , Luo Jing , Main Robert , McKee James , Pen Ue-Li , Simard Dana , van Kerkwijk Marten H
Published: September 2021

Propagation effects in the interstellar medium and intrinsic profile changes can cause variability in the timing of pulsars, which limits the accuracy of fundamental science done via pulsar timing. One of the best timing pulsars, PSR J1713+0747, has gone through two ‘dip’ events in its dispersion measure (DM) time series. If these events reflect real changes in electron column density, they should lead to multiple imaging. We show that the events are well fitted by an underdense corrugated sheet model, and look for associated variability in the pulse profile using principal component analysis. We find that there are transient pulse profile variations, but they vary in concert with the DM, unlike what is expected from lensing due to a corrugated sheet. The change is consistent in shape across profiles from both the Green Bank and Arecibo radio observatories, and its amplitude appears to be achromatic across the 820-MHz, 1.4-GHz, and 2.3-GHz bands, again unlike expected from interference between lensed images. This result is puzzling. We note that some of the predicted lensing effects would need higher time and frequency resolution data than used in this analysis. Future events appear likely, and storing baseband data or keeping multiple time–frequency resolutions will allow more in-depth study of propagation effects and hence improvements to pulsar timing accuracy.
NuSTAR monitoring of MAXI J1348−630: evidence of high density disc reflection
Authors: Chakraborty Sudip , Ratheesh Ajay , Bhattacharyya Sudip , Tomsick John A , Tombesi Francesco , Fukumura Keigo , Jaisawal Gaurava K
Published: September 2021

We present the broad-band spectral analysis of all the six hard, intermediate, and soft state NuSTAR observations of the recently discovered transient black hole X-ray binary MAXI J1348−630 during its first outburst in 2019. We first model the data with a combination of a multicolour disc and a relativistic blurred reflection, and, whenever needed, a distant reflection. We find that this simple model scheme is inadequate in explaining the spectra, resulting in a very high iron abundance. We therefore explore the possibility of reflection from a high-density disc. We use two different sets of models to describe the high-density disc reflection: relxill-based reflection models, and reflionx-based ones. The reflionx-based high-density disc reflection models bring down the iron abundance to around the solar value, while the density is found to be $10^{20.3-21.4}\, \rm cm^{-3}$. We also find evidence of a high-velocity outflow in the form of ∼7.3 keV absorption lines. The consistency between the best-fitting parameters for different epochs and the statistical significance of the corresponding model indicates the existence of high-density disc reflection in MAXI J1348−630.
SCSS-Net: solar corona structures segmentation by deep learning
Authors: Mackovjak Šimon , Harman Martin , Maslej-Krešňáková Viera , Butka Peter
Published: September 2021

Structures in the solar corona are the main drivers of space weather processes that might directly or indirectly affect the Earth. Thanks to the most recent space-based solar observatories, with capabilities to acquire high-resolution images continuously, the structures in the solar corona can be monitored over the years with a time resolution of minutes. For this purpose, we have developed a method for automatic segmentation of solar corona structures observed in the EUV spectrum that is based on a deep-learning approach utilizing convolutional neural networks. The available input data sets have been examined together with our own data set based on the manual annotation of the target structures. Indeed, the input data set is the main limitation of the developed model’s performance. Our SCSS-Net model provides results for coronal holes and active regions that could be compared with other generally used methods for automatic segmentation. Even more, it provides a universal procedure to identify structures in the solar corona with the help of the transfer learning technique. The outputs of the model can be then used for further statistical studies of connections between solar activity and the influence of space weather on Earth.
The role of scatter and satellites in shaping the large-scale clustering of X-ray AGN as a function of host galaxy stellar mass
Authors: Viitanen A , Allevato V , Finoguenov A , Shankar F , Marsden C
Published: September 2021

The co-evolution between central supermassive black holes (BHs), their host galaxies, and dark matter haloes is still a matter of intense debate. Present theoretical models suffer from large uncertainties and degeneracies, for example, between the fraction of accreting sources and their characteristic accretion rate. In recent work, we showed that active galactic nuclei (AGNs) clustering represents a powerful tool to break degeneracies when analysed in terms of mean BH mass, and that AGN bias at fixed stellar mass is largely independent of most of the input parameters, such as the AGN duty cycle and the mean scaling between BH mass and host galaxy stellar mass. In this paper, we take advantage of our improved semi-empirical methodology and recent clustering data derived from large AGN samples at z ∼ 1.2, demonstrate that the AGN bias as a function of host galaxy stellar mass is a crucial diagnostic of the BH–galaxy connection, and is highly dependent on the scatter around the BH mass–galaxy mass scaling relation and on the relative fraction of satellite and central active BHs. Current data at z ∼ 1.2 favour relatively high values of AGN in satellites, pointing to a major role of disc instabilities in triggering AGN, unless a high minimum host halo mass is assumed. The data are not decisive on the magnitude/covariance of the BH–galaxy scatter at z ∼ 1.2 and intermediate host masses $M_\mathrm{star} \lesssim 10^{11} \, \mathrm{M}_\mathrm{star}$. However, future surveys like Euclid/LSST will be pivotal in shedding light on the BH–galaxy co-evolution.
FAST early pulsar discoveries: Effelsberg follow-up
Authors: Cruces M , Champion D J , Li (李 菂) D , Kramer M , Zhu W W , Wang P , Cameron A D , Chen Y T , Hobbs G , Freire P C C , Graikou E , Krco M , Liu Z J , Miao C C , Niu J , Pan Z C , Qian L , Xue M Y , Xie X Y , You S P , Yu X H , Yuan M , Yue Y L , Zhu Y ,   CRAFTS collaboration, Lackeos K , Porayko N , Wongphecauxon J , Main R
Published: September 2021

We report the follow-up of 10 pulsars discovered by the Five-hundred-metre Aperture Spherical radio-Telescope (FAST) during its commissioning. The pulsars were discovered at a frequency of 500-MHz using the ultrawide-band (UWB) receiver in drift-scan mode, as part of the Commensal Radio Astronomy FAST Survey (CRAFTS). We carried out the timing campaign with the 100-m Effelsberg radio-telescope at L-band around 1.36 GHz. Along with 11 FAST pulsars previously reported, FAST seems to be uncovering a population of older pulsars, bordering and/or even across the pulsar death-lines. We report here two sources with notable characteristics. PSR J1951+4724 is a young and energetic pulsar with nearly 100 per cent of linearly polarized flux density and visible up to an observing frequency of 8 GHz. PSR J2338+4818, a mildly recycled pulsar in a 95.2-d orbit with a Carbon–Oxygen white dwarf (WD) companion of $\gtrsim 1\, \rm {M}_{\odot }$, based on estimates from the mass function. This system is the widest WD binary with the most massive companion known to-date. Conspicuous discrepancy was found between estimations based on NE2001 and YMW16 electron density models, which can be attributed to underrepresentation of pulsars in the sky region between Galactic longitudes 70° < l < 100°. This work represents one of the early CRAFTS results, which start to show potential to substantially enrich the pulsar sample and refine the Galactic electron density model.
Host galaxy line diagnostics for the candidate tidal disruption events XMMSL1 J111527.3+180638 and PTF09axc
Authors: Inkenhaag Anne , Jonker Peter G , Cannizzaro Giacomo , Mata Sánchez Daniel , Saxton Richard D
Published: September 2021

We present results of our analysis of spectra of the host galaxies of the candidate tidal disruption events (TDEs) XMMSL1 J111527.3+180638 and PTF09axc to determine the nature of these transients. We subtract the starlight component from the host galaxy spectra to determine the origin of the nuclear emission lines. Using a Baldwin–Phillips–Terlevich (BPT) diagram, we conclude that the host galaxy of XMMSL1 J111527.3+180638 is classified as a Seyfert galaxy, suggesting this transient is likely to be caused by (extreme) variability in the active galactic nucleus. We find that the host of PTF09axc falls in the ‘star-forming’ region of the BPT diagram, implying that the transient is a strong TDE candidate. For both galaxies, we find a WISE colour difference of W1 − W2 < 0.8, which means there is no indication of a dusty torus and therefore an active galactic nucleus, seemingly contradicting our BPT finding for the host of XMMSL1 J111527.3+180638. We discuss possible reasons for the discrepant results obtained through these two methods.
High-dispersion spectroscopy of AE Aquarii – II. Evidence of material orbiting the primary star
Authors: Ramírez S H , Echevarría J
Published: September 2021

We present a second paper related to the analyses of high-dispersion spectroscopic observations of the magnetic cataclysmic variable AE Aquarii. We focus our efforts on the study of the emission lines and their radial velocities. We detect a sinusoidal behaviour, in several of the observing runs, with variable amplitudes. Of those runs presented, the velocity curve of 2000 August shows less instability in the emission material. In this case, we obtain K1 = 114 ± 8 km s−1, which we take as our best value for the radial velocity of the primary. This result is consistent within 2σ with previously published values obtained using indirect methods. We interpret this consistency as observational evidence of material orbiting the rapidly rotating primary star. We present a Doppler tomography study, which shows that the H α emission is primarily concentrated within a blob in the lower left quadrant, a structure similar to that predicted by the propeller model. However, for 2000 August, we find the emission centred around the position of the white dwarf, which supports the possibility of the K1 value of this run of being a valid approximation of the orbital motion of the white dwarf.
Numerical convergence of pre-initial conditions on dark matter halo properties
Authors: Zhang Tianchi , Liao Shihong , Li Ming , Zhang Jiajun
Published: September 2021

Generating pre-initial conditions (or particle loads) is the very first step to set up a cosmological N-body simulation. In this work, we revisit the numerical convergence of pre-initial conditions on dark matter halo properties using a set of simulations which only differs in initial particle loads, i.e. grid, glass, and the newly introduced capacity constrained Voronoi tessellation (CCVT). We find that the median halo properties agree fairly well (i.e. within a convergence level of a few per cent) among simulations running from different initial loads. We also notice that for some individual haloes cross-matched among different simulations, the relative difference of their properties sometimes can be several tens of per cent. By looking at the evolution history of these poorly converged haloes, we find that they are usually merging haloes or haloes have experienced recent merger events, and their merging processes in different simulations are out-of-sync, making the convergence of halo properties become poor temporarily. We show that, comparing to the simulation starting with an anisotropic grid load, the simulation with an isotropic CCVT load converges slightly better to the simulation with a glass load, which is also isotropic. Among simulations with different pre-initial conditions, haloes in higher density environments tend to have their properties converged slightly better. Our results confirm that CCVT loads behave as well as the widely used grid and glass loads at small scales, and for the first time we quantify the convergence of two independent isotropic particle loads (i.e. glass and CCVT) on halo properties.
A pathogenic DMC1 frameshift mutation causes nonobstructive azoospermia but not primary ovarian insufficiency in humans
Authors: Cao Dandan , Shi Fu , Guo Chenxi , Liu Ye , Lin Zexiong , Zhang Juanhui , Li Raymond Hang Wun , Yao Yuanqing , Liu Kui , Ng Ernest Hung Yu , Yeung William Shu Biu , Wang Tianren
Published: September 2021

Nonobstructive azoospermia (NOA) and diminished ovarian reserve (DOR) are two disorders that can lead to infertility in males and females. Genetic factors have been identified to contribute to NOA and DOR. However, the same genetic factor that can cause both NOA and DOR remains largely unknown. To explore the candidate pathogenic gene that causes both NOA and DOR, we conducted whole-exome sequencing (WES) in a non-consanguineous family with two daughters with DOR and a son with NOA. We detected one pathogenic frameshift variant (NM_007068:c.28delG, p. Glu10Asnfs*31) following a recessive inheritance mode in a meiosis gene DMC1 (DNA meiotic recombinase 1). Clinical analysis showed reduced antral follicle number in both daughters with DOR, but metaphase II oocytes could be retrieved from one of them. For the son with NOA, no spermatozoa were found after microsurgical testicular sperm extraction. A further homozygous Dmc1 knockout mice study demonstrated total failure of follicle development and spermatogenesis. These results revealed a discrepancy of DMC1 action between mice and humans. In humans, DMC1 is required for spermatogenesis but is dispensable for oogenesis, although the loss of function of this gene may lead to DOR. To our knowledge, this is the first report on the homozygous frameshift mutation as causative for both NOA and DOR and demonstrating that DMC1 is dispensable in human oogenesis.
A Grid in Flux: Sound and Timing in Electronic Dance Music
Authors: Brøvig-Hanssen Ragnhild , Sandvik Bjørnar , Aareskjold-Drecker Jon Marius , Danielsen Anne
Published: September 2021

Researchers have argued that temporal microdeviations from the metric grid, such as those produced by musicians in performance, are crucial to making a musical rhythm groovy and danceable. It is curious, then, that the music currently dominating the dance floor, “electronic dance music” or EDM, is typically characterized by grid-based rhythms. But is such a “mechanistic,” grid-based aesthetic necessarily devoid of microrhythmic nuance? In this article, we aim to show that the microrhythmic component of an engaging groove involves the manipulation of more than simply the onset locations of rhythmic events—the sonic features fundamentally contribute to shaping the groove as well. In particular, we seek to demonstrate that EDM producers, with their preference for a grid-based microtiming aesthetic, are very sensitive to and adept at manipulating such sonic features for expressive effect. Drawing on interviews with EDM producers, we show that producers are often concerned with both sonic and temporal features, as well as their interactions. We argue that sonic features are crucial to shaping groove and feel at the micro level of rhythm. Moreover, such features also tend to introduce an indirect microtiming aspect to the grid-based aesthetic of EDM through the ways in which they shape timing at the perceptual level.
Rapid prototyping of arbitrary 2D and 3D wireframe DNA origami
Authors: Jun Hyungmin , Wang Xiao , Parsons Molly F , Bricker William P , John Torsten , Li Shanshan , Jackson Steve , Chiu Wah , Bathe Mark
Published: September 2021

Wireframe DNA origami assemblies can now be programmed automatically from the top-down using simple wireframe target geometries, or meshes, in 2D and 3D, using either rigid, six-helix bundle (6HB) or more compliant, two-helix bundle (DX) edges. While these assemblies have numerous applications in nanoscale materials fabrication due to their nanoscale spatial addressability and high degree of customization, no easy-to-use graphical user interface software yet exists to deploy these algorithmic approaches within a single, standalone interface. Further, top-down sequence design of 3D DX-based objects previously enabled by DAEDALUS was limited to discrete edge lengths and uniform vertex angles, limiting the scope of objects that can be designed. Here, we introduce the open-source software package ATHENA with a graphical user interface that automatically renders single-stranded DNA scaffold routing and staple strand sequences for any target wireframe DNA origami using DX or 6HB edges, including irregular, asymmetric DX-based polyhedra with variable edge lengths and vertices demonstrated experimentally, which significantly expands the set of possible 3D DNA-based assemblies that can be designed. ATHENA also enables external editing of sequences using caDNAno, demonstrated using asymmetric nanoscale positioning of gold nanoparticles, as well as providing atomic-level models for molecular dynamics, coarse-grained dynamics with oxDNA, and other computational chemistry simulation approaches.
Theoretical basis for stabilizing messenger RNA through secondary structure design
Authors: Wayment-Steele Hannah K , Kim Do Soon , Choe Christian A , Nicol John J , Wellington-Oguri Roger , Watkins Andrew M , Parra Sperberg R Andres , Huang Po-Ssu , Participants Eterna , Das Rhiju
Published: September 2021

RNA hydrolysis presents problems in manufacturing, long-term storage, world-wide delivery and in vivo stability of messenger RNA (mRNA)-based vaccines and therapeutics. A largely unexplored strategy to reduce mRNA hydrolysis is to redesign RNAs to form double-stranded regions, which are protected from in-line cleavage and enzymatic degradation, while coding for the same proteins. The amount of stabilization that this strategy can deliver and the most effective algorithmic approach to achieve stabilization remain poorly understood. Here, we present simple calculations for estimating RNA stability against hydrolysis, and a model that links the average unpaired probability of an mRNA, or AUP, to its overall hydrolysis rate. To characterize the stabilization achievable through structure design, we compare AUP optimization by conventional mRNA design methods to results from more computationally sophisticated algorithms and crowdsourcing through the OpenVaccine challenge on the Eterna platform. We find that rational design on Eterna and the more sophisticated algorithms lead to constructs with low AUP, which we term ‘superfolder’ mRNAs. These designs exhibit a wide diversity of sequence and structure features that may be desirable for translation, biophysical size, and immunogenicity. Furthermore, their folding is robust to temperature, computer modeling method, choice of flanking untranslated regions, and changes in target protein sequence, as illustrated by rapid redesign of superfolder mRNAs for B.1.351, P.1 and B.1.1.7 variants of the prefusion-stabilized SARS-CoV-2 spike protein. Increases in in vitro mRNA half-life by at least two-fold appear immediately achievable.
Impact of alanyl-tRNA synthetase editing deficiency in yeast
Authors: Zhang Hong , Wu Jiang , Lyu Zhihui , Ling Jiqiang
Published: September 2021

Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes that provide the ribosome with aminoacyl-tRNA substrates for protein synthesis. Mutations in aaRSs lead to various neurological disorders in humans. Many aaRSs utilize editing to prevent error propagation during translation. Editing defects in alanyl-tRNA synthetase (AlaRS) cause neurodegeneration and cardioproteinopathy in mice and are associated with microcephaly in human patients. The cellular impact of AlaRS editing deficiency in eukaryotes remains unclear. Here we use yeast as a model organism to systematically investigate the physiological role of AlaRS editing. Our RNA sequencing and quantitative proteomics results reveal that AlaRS editing defects surprisingly activate the general amino acid control pathway and attenuate the heatshock response. We have confirmed these results with reporter and growth assays. In addition, AlaRS editing defects downregulate carbon metabolism and attenuate protein synthesis. Supplying yeast cells with extra carbon source partially rescues the heat sensitivity caused by AlaRS editing deficiency. These findings are in stark contrast with the cellular effects caused by editing deficiency in other aaRSs. Our study therefore highlights the idiosyncratic role of AlaRS editing compared with other aaRSs and provides a model for the physiological impact caused by the lack of AlaRS editing.
Identification of host tRNAs preferentially recognized by the Plasmodium surface protein tRip
Authors: Cela Marta , Théobald-Dietrich Anne , Rudinger-Thirion Joëlle , Wolff Philippe , Geslain Renaud , Frugier Magali
Published: September 2021

Malaria is a life-threatening and devastating parasitic disease. Our previous work showed that parasite development requires the import of exogenous transfer RNAs (tRNAs), which represents a novel and unique form of host–pathogen interaction, as well as a potentially druggable target. This import is mediated by tRip (tRNA import protein), a membrane protein located on the parasite surface. tRip displays an extracellular domain homologous to the well-characterized OB-fold tRNA-binding domain, a structural motif known to indiscriminately interact with tRNAs. We used MIST (Microarray Identification of Shifted tRNAs), a previously established in vitro approach, to systematically assess the specificity of complexes between native Homo sapiens tRNAs and recombinant Plasmodium falciparum tRip. We demonstrate that tRip unexpectedly binds to host tRNAs with a wide range of affinities, suggesting that only a small subset of human tRNAs is preferentially imported into the parasite. In particular, we show with in vitro transcribed constructs that tRip does not bind specific tRNAs solely based on their primary sequence, hinting that post-transcriptional modifications modulate the formation of our host/parasite molecular complex. Finally, we discuss the potential utilization of the most efficient tRip ligands for the translation of the parasite's genetic information.
Comprehensive characterization of somatic variants associated with intronic polyadenylation in human cancers
Authors: Zhao Zhaozhao , Xu Qiushi , Wei Ran , Huang Leihuan , Wang Weixu , Wei Gang , Ni Ting
Published: September 2021

Somatic single nucleotide variants (SNVs) in cancer genome affect gene expression through various mechanisms depending on their genomic location. While somatic SNVs near canonical splice sites have been reported to cause abnormal splicing of cancer-related genes, whether these SNVs can affect gene expression through other mechanisms remains an open question. Here, we analyzed RNA sequencing and exome data from 4,998 cancer patients covering ten cancer types and identified 152 somatic SNVs near splice sites that were associated with abnormal intronic polyadenylation (IPA). IPA-associated somatic variants favored the localization near the donor splice sites compared to the acceptor splice sites. A proportion of SNV-associated IPA events overlapped with premature cleavage and polyadenylation events triggered by U1 small nuclear ribonucleoproteins (snRNP) inhibition. GC content, intron length and polyadenylation signal were three genomic features that differentiated between SNV-associated IPA and intron retention. Notably, IPA-associated SNVs were enriched in tumor suppressor genes (TSGs), including the well-known TSGs such as PTEN and CDH1 with recurrent SNV-associated IPA events. Minigene assay confirmed that SNVs from PTEN, CDH1, VEGFA, GRHL2, CUL3 and WWC2 could lead to IPA. This work reveals that IPA acts as a novel mechanism explaining the functional consequence of somatic SNVs in human cancer.
Replication-dependent cytotoxicity and Spartan-mediated repair of trapped PARP1–DNA complexes
Authors: Saha Liton Kumar , Murai Yasuhisa , Saha Sourav , Jo Ukhyun , Tsuda Masataka , Takeda Shunichi , Pommier Yves
Published: September 2021

The antitumor activity of poly(ADP-ribose) polymerase inhibitors (PARPis) has been ascribed to PARP trapping, which consists in tight DNA–protein complexes. Here we demonstrate that the cytotoxicity of talazoparib and olaparib results from DNA replication. To elucidate the repair of PARP1–DNA complexes associated with replication in human TK6 and chicken DT40 lymphoblastoid cells, we explored the role of Spartan (SPRTN), a metalloprotease associated with DNA replication, which removes proteins forming DPCs. We find that SPRTN-deficient cells are hypersensitive to talazoparib and olaparib, but not to veliparib, a weak PARP trapper. SPRTN-deficient cells exhibit delayed clearance of trapped PARP1 and increased replication fork stalling upon talazoparib and olaparib treatment. We also show that SPRTN interacts with PARP1 and forms nuclear foci that colocalize with the replicative cell division cycle 45 protein (CDC45) in response to talazoparib. Additionally, SPRTN is deubiquitinated and epistatic with translesion synthesis (TLS) in response to talazoparib. Our results demonstrate that SPRTN is recruited to trapped PARP1 in S-phase to assist in the excision and replication bypass of PARP1–DNA complexes.
GRAND: a database of gene regulatory network models across human conditions
Authors: Ben Guebila Marouen , Lopes-Ramos Camila M , Weighill Deborah , Sonawane Abhijeet Rajendra , Burkholz Rebekka , Shamsaei Behrouz , Platig John , Glass Kimberly , Kuijjer Marieke L , Quackenbush John
Published: September 2021

Gene regulation plays a fundamental role in shaping tissue identity, function, and response to perturbation. Regulatory processes are controlled by complex networks of interacting elements, including transcription factors, miRNAs and their target genes. The structure of these networks helps to determine phenotypes and can ultimately influence the development of disease or response to therapy. We developed GRAND (https://grand.networkmedicine.org) as a database for computationally-inferred, context-specific gene regulatory network models that can be compared between biological states, or used to predict which drugs produce changes in regulatory network structure. The database includes 12 468 genome-scale networks covering 36 human tissues, 28 cancers, 1378 unperturbed cell lines, as well as 173 013 TF and gene targeting scores for 2858 small molecule-induced cell line perturbation paired with phenotypic information. GRAND allows the networks to be queried using phenotypic information and visualized using a variety of interactive tools. In addition, it includes a web application that matches disease states to potentially therapeutic small molecule drugs using regulatory network properties.
ViMIC: a database of human disease-related virus mutations, integration sites and cis-effects
Authors: Wang Ying , Tong Yuantao , Zhang Zeyu , Zheng Rongbin , Huang Danqi , Yang Jinxuan , Zong Hui , Tan Fanglin , Xie Yujia , Huang Honglian , Zhang Xiaoyan
Published: September 2021

Molecular mechanisms of virus-related diseases involve multiple factors, including viral mutation accumulation and integration of a viral genome into the host DNA. With increasing attention being paid to virus-mediated pathogenesis and the development of many useful technologies to identify virus mutations (VMs) and viral integration sites (VISs), much research on these topics is available in PubMed. However, knowledge of VMs and VISs is widely scattered in numerous published papers which lack standardization, integration and curation. To address these challenges, we built a pilot database of human disease-related Virus Mutations, Integration sites and Cis-effects (ViMIC), which specializes in three features: virus mutation sites, viral integration sites and target genes. In total, the ViMIC provides information on 31 712 VMs entries, 105 624 VISs, 16 310 viral target genes and 1 110 015 virus sequences of eight viruses in 77 human diseases obtained from the public domain. Furthermore, in ViMIC users are allowed to explore the cis-effects of virus-host interactions by surveying 78 histone modifications, binding of 1358 transcription regulators and chromatin accessibility on these VISs. We believe ViMIC will become a valuable resource for the virus research community. The database is available at http://bmtongji.cn/ViMIC/index.php.
CancerMIRNome: an interactive analysis and visualization database for miRNome profiles of human cancer
Authors: Li Ruidong , Qu Han , Wang Shibo , Chater John M , Wang Xuesong , Cui Yanru , Yu Lei , Zhou Rui , Jia Qiong , Traband Ryan , Wang Meiyue , Xie Weibo , Yuan Dongbo , Zhu Jianguo , Zhong Wei-De , Jia Zhenyu
Published: September 2021

MicroRNAs (miRNAs), which play critical roles in gene regulatory networks, have emerged as promising diagnostic and prognostic biomarkers for human cancer. In particular, circulating miRNAs that are secreted into circulation exist in remarkably stable forms, and have enormous potential to be leveraged as non-invasive biomarkers for early cancer detection. Novel and user-friendly tools are desperately needed to facilitate data mining of the vast amount of miRNA expression data from The Cancer Genome Atlas (TCGA) and large-scale circulating miRNA profiling studies. To fill this void, we developed CancerMIRNome, a comprehensive database for the interactive analysis and visualization of miRNA expression profiles based on 10 554 samples from 33 TCGA projects and 28 633 samples from 40 public circulating miRNome datasets. A series of cutting-edge bioinformatics tools and machine learning algorithms have been packaged in CancerMIRNome, allowing for the pan-cancer analysis of a miRNA of interest across multiple cancer types and the comprehensive analysis of miRNome profiles to identify dysregulated miRNAs and develop diagnostic or prognostic signatures. The data analysis and visualization modules will greatly facilitate the exploit of the valuable resources and promote translational application of miRNA biomarkers in cancer. The CancerMIRNome database is publicly available at http://bioinfo.jialab-ucr.org/CancerMIRNome.
XAB2 promotes Ku eviction from single-ended DNA double-strand breaks independently of the ATM kinase
Authors: Sharma Abhishek Bharadwaj , Erasimus Hélène , Pinto Lia , Caron Marie-Christine , Gopaul Diyavarshini , Peterlini Thibaut , Neumann Katrin , Nazarov Petr V , Fritah Sabrina , Klink Barbara , Herold-Mende Christel C , Niclou Simone P , Pasero Philippe , Calsou Patrick , Masson Jean-Yves , Britton Sébastien , Van Dyck Eric
Published: September 2021

Replication-associated single-ended DNA double-strand breaks (seDSBs) are repaired predominantly through RAD51-mediated homologous recombination (HR). Removal of the non-homologous end-joining (NHEJ) factor Ku from resected seDSB ends is crucial for HR. The coordinated actions of MRE11-CtIP nuclease activities orchestrated by ATM define one pathway for Ku eviction. Here, we identify the pre-mRNA splicing protein XAB2 as a factor required for resistance to seDSBs induced by the chemotherapeutic alkylator temozolomide. Moreover, we show that XAB2 prevents Ku retention and abortive HR at seDSBs induced by temozolomide and camptothecin, via a pathway that operates in parallel to the ATM-CtIP-MRE11 axis. Although XAB2 depletion preserved RAD51 focus formation, the resulting RAD51-ssDNA associations were unproductive, leading to increased NHEJ engagement in S/G2 and genetic instability. Overexpression of RAD51 or RAD52 rescued the XAB2 defects and XAB2 loss was synthetically lethal with RAD52 inhibition, providing potential perspectives in cancer therapy.