Hydrodynamical turbulence in eccentric circumbinary discs and its impact on the in situ formation of circumbinary planets

Eccentric gaseous discs are unstable to a parametric instability involving the resonant interaction between inertial-gravity waves and the eccentric mode in the disc. We present 3D global hydrodynamical simulations of inviscid circumbinary discs that form an inner cavity and become eccentric through interaction with the central binary. The parametric instability grows and generates turbulence that transports angular momentum with stress parameter $\alpha \sim 5 \times 10^{-3}$ at distances $\lesssim 7 \;a_{bin}$, where $a_{bin}$ is the binary semi-major axis. Vertical turbulent diffusion occurs at a rate corresponding to $\alpha_{diff}\sim 1-2\times 10^{-3}$. We examine the impact of turbulent diffusion on the vertical settling of pebbles, and on the rate of pebble accretion by embedded planets. In steady state, dust particles with Stokes numbers ${\it St} \lesssim 0.1$ form a layer of finite thickness $H_d \gtrsim 0.1 H$, where $H$ is the gas scale height. Pebble accretion efficiency is then reduced by a factor $r_{acc}/H_d$, where $r_{acc}$ is the accretion radius, compared to the rate in a laminar disc. For accreting core masses with $m_p \lesssim 0.1\; M_\oplus$, pebble accretion for particles with ${\it St} \gtrsim 0.5$ is also reduced because of velocity kicks induced by the turbulence. These effects combine to make the time needed by a Ceres-mass object to grow to the pebble isolation mass, when significant gas accretion can occur, longer than typical disc lifetimes. Hence, the origins of circumbinary planets orbiting close to their central binary systems, as discovered by the Kepler mission, are difficult to explain using an in situ model that invokes a combination of the streaming instability and pebble accretion.Comment: Accepted in MNRA

HTR4 gene structure and altered expression in the developing lung

Background: Meta-analyses of genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) spanning the 5-hydroxytryptamine receptor 4 (5-HT4R) gene (HTR4) associated with lung function. The aims of this study were to i) investigate the expression profile of HTR4 in adult and fetal lung tissue and cultured airway cells, ii) further define HTR4 gene structure and iii) explore the potential functional implications of key SNPs using a bioinformatic approach

Low-mass planet migration in three-dimensional wind-driven inviscid discs: a negative corotation torque

We present simulations of low-mass planet–disc interactions in inviscid three-dimensional discs. We show that a wind-driven laminar accretion flow through the surface layers of the disc does not significantly modify the migration torque experienced by embedded planets. More importantly, we find that 3D effects lead to a dramatic change in the behaviour of the dynamical corotation torque compared to earlier 2D theory and simulations. Although it was previously shown that the dynamical corotation torque could act to slow and essentially stall the inward migration of a low-mass planet, our results in 3D show that the dynamical corotation torque has the complete opposite effect and speeds up inward migration. Our numerical experiments implicate buoyancy resonances as the cause. These have two effects: (i) they exert a direct torque on the planet, whose magnitude relative to the Lindblad torque is measured in our simulations to be small; (ii) they torque the gas librating on horseshoe orbits in the corotation region and drive evolution of its vortensity, leading to the negative dynamical corotation torque. This indicates that at low turbulent viscosity, the detailed vertical thermal structure of the protoplanetary disc plays an important role in determining the migration behaviour of embedded planets. If this result holds up under a more refined treatment of disc thermal evolution, then it has important implications for understanding the formation and early evolution of planetary systems

A reference relative time-scale as an alternative to chronological age for cohorts with long follow-up

Background: Epidemiologists have debated the appropriate time-scale for cohort survival studies; chronological age or time-on-study being two such time-scales. Importantly, assessment of risk factors may depend on the choice of time-scale. Recently, chronological or attained age has gained support but a case can be made for a ‘reference relative time-scale’ as an alternative which circumvents difficulties that arise with this and other scales. The reference relative time of an individual participant is the integral of a reference population hazard function between time of entry and time of exit of the individual. The objective here is to describe the reference relative time-scale, illustrate its use, make comparison with attained age by simulation and explain its relationship to modern and traditional epidemiologic methods. Results: A comparison was made between two models; a stratified Cox model with age as the time-scale versus an un-stratified Cox model using the reference relative time-scale. The illustrative comparison used a UK cohort of cotton workers, with differing ages at entry to the study, with accrual over a time period and with long follow-up. Additionally, exponential and Weibull models were fitted since the reference relative time-scale analysis need not be restricted to the Cox model. A simulation study showed that analysis using the reference relative time-scale and analysis using chronological age had very similar power to detect a significant risk factor and both were equally unbiased. Further, the analysis using the reference relative time-scale supported fully-parametric survival modelling and allowed percentile predictions and mortality curves to be constructed. Conclusions: The reference relative time-scale was a viable alternative to chronological age, led to simplification of the modelling process and possessed the defined features of a good time-scale as defined in reliability theory. The reference relative time-scale has several interpretations and provides a unifying concept that links contemporary approaches in survival and reliability analysis to the traditional epidemiologic methods of Poisson regression and standardised mortality ratios. The community of practitioners has not previously made this connection

Vertical settling of pebbles in turbulent circumbinary discs and the in situ formation of circumbinary planets

The inner-most regions of circumbinary discs are unstable to a parametric instability whose non-linear evolution is hydrodynamical turbulence. This results in significant particle stirring, impacting on planetary growth processes such as the streaming instability or pebble accretion. In this paper, we present the results of three-dimensional, inviscid global hydrodynamical simulations of circumbinary discs with embedded particles of 1 cm size. Hydrodynamical turbulence develops in the disc, and we examine the effect of the particle back-reaction on vertical dust. We find that higher solid-to-gas ratios lead to smaller gas vertical velocity fluctuations, and therefore to smaller dust scale heights. For a metallicity Z = 0.1, the dust scale height near the edge of the tidally-truncated cavity is ∼80 per cent of the gas scale height, such that growing a Ceres-mass object to a 10 M⊕ core via pebble accretion would take longer than the disc lifetime. Collision velocities for small particles are also higher than the critical velocity for fragmentation, which precludes grain growth and the possibility of forming a massive planetesimal seed for pebble accretion. At larger distances from the binary, turbulence is weak enough to enable not only efficient pebble accretion but also grain growth to sizes required to trigger the streaming instability. In these regions, an in-situ formation scenario of circumbinary planets involving the streaming instability to form a massive planetesimal followed by pebble accretion on to this core is viable. In that case, planetary migration has to be invoked to explain the presence of circumbinary planets at their observed locations

Role of transglutaminase 2 in A1 adenosine receptor- and β2 -adrenoceptor-mediated pharmacological pre- and post-conditioning against hypoxia-reoxygenation-induced cell death in H9c2 cells

Pharmacologically-induced pre- and post-conditioning represent attractive therapeutic strategies to reduce ischaemia/reperfusion injury during cardiac surgery and following myocardial infarction. We have previously reported that transglutaminase 2 (TG2) activity is modulated by the A1 adenosine receptor and β2-adrenoceptor in H9c2 cardiomyoblasts. The primary aim of this study was to determine the role of TG2 in A1 adenosine receptor and β2-adrenoceptor-induced pharmacological pre- and post-conditioning in the H9c2 cells. H9c2 cells were exposed to 8 h hypoxia (1% O2) followed by 18 h reoxygenation, after which cell viability was assessed by monitoring mitochondrial reduction of MTT, lactate dehydrogenase release and caspase-3 activation. N6-cyclopentyladenosine (CPA; A1 adenosine receptor agonist), formoterol (β2-adrenoceptor agonist) or isoprenaline (non-selective β-adrenoceptor agonist) were added before hypoxia/reoxygenation (pre-conditioning) or at the start of reoxygenation following hypoxia (post-conditioning). Pharmacological pre- and post-conditioning with CPA and isoprenaline significantly reduced hypoxia/reoxygenation-induced cell death. In contrast, formoterol did not elicit protection. Pre-treatment with pertussis toxin (Gi/o-protein inhibitor), DPCPX (A1 adenosine receptor antagonist) or TG2 inhibitors (Z-DON and R283) attenuated the A1 adenosine receptor-induced pharmacological pre- and post-conditioning. Similarly, pertussis toxin, ICI 118,551 (β2-adrenoceptor antagonist) or TG2 inhibition attenuated the isoprenaline-induced cell survival. Knockdown of TG2 using small interfering RNA (siRNA) attenuated CPA and isoprenaline-induced pharmacological pre- and post-conditioning. Finally, proteomic analysis following isoprenaline treatment identified known (e.g. protein S100-A6) and novel (e.g. adenine phosphoribosyltransferase) protein substrates for TG2. These results have shown that A1 adenosine receptor and β2-adrenoceptor-induced protection against simulated hypoxia/reoxygenation occurs in a TG2 and Gi/o-protein dependent manner in H9c2 cardiomyoblasts

Ab initio structure prediction methods for battery materials a review of recent computational efforts to predict the atomic level structure and bonding in materials for rechargeable batteries

Portable electronic devices, electric vehicles and stationary energy storage applications, which encourage carbon-neutral energy alternatives, are driving demand for batteries that have concurrently higher energy densities, faster charging rates, safer operation and lower prices. These demands can no longer be met by incrementally improving existing technologies but require the discovery of new materials with exceptional properties. Experimental materials discovery is both expensive and time consuming: before the efficacy of a new battery material can be assessed, its synthesis and stability must be well-understood. Computational materials modelling can expedite this process by predicting novel materials, both in stand-alone theoretical calculations and in tandem with experiments. In this review, we describe a materials discovery framework based on density functional theory (DFT) to predict the properties of electrode and solid-electrolyte materials and validate these predictions experimentally. First, we discuss crystal structure prediction using the Ab initio random structure searching (AIRSS) method. Next, we describe how DFT results allow us to predict which phases form during electrode cycling, as well as the electrode voltage profile and maximum theoretical capacity. We go on to explain how DFT can be used to simulate experimentally measurable properties such as nuclear magnetic resonance (NMR) spectra and ionic conductivities. We illustrate the described workflow with multiple experimentally validated examples: materials for lithium-ion and sodium-ion anodes and lithium-ion solid electrolytes. These examples highlight the power of combining computation with experiment to advance battery materials research.(1) Gates Cambridge Trust, University of Cambridge, UK (2) EPSRC Centre for Doctoral Training in Computational Methods for Materials Science, UK, Grant No. EP/L015552/1. (3) Winton Programme for the Physics of Sustainability, University of Cambridge, UK (4) Sims Fund, University of Cambridge, UK (5) EPSRC Grant No. EP/P003532/1 (6) EPSRC Collaborative Computational Projects on the Electronic Structure of Condensed Matter (CCP9), Grant No. EP/M022595/1, and NMR crystallography, Grant No. EP/M022501/1 (7) Computing resources on the Tier 1 resource ARCHER were provided through the UKCP EPSRC High-End computational consortium (EP/P022561/1) and on the Tier 2 resources HPC Midlands+ (EP/P020232/1) and CSD3 (EP/P020259/1)

TRIM5α requires Ube2W to anchor Lys63-linked ubiquitin chains and restrict reverse transcription

TRIM5α is an antiviral, cytoplasmic, E3 ubiquitin (Ub) ligase that assembles on incoming retroviral capsids and induces their premature dissociation. It inhibits reverse transcription of the viral genome and can also synthesize unanchored polyubiquitin (polyUb) chains to stimulate innate immune responses. Here, we show that TRIM5α employs the E2 Ub-conjugating enzyme Ube2W to anchor the Lys63-linked polyUb chains in a process of TRIM5α auto-ubiquitination. Chain anchoring is initiated, in cells and in vitro, through Ube2W-catalyzed monoubiquitination of TRIM5α. This modification serves as a substrate for the elongation of anchored Lys63-linked polyUb chains, catalyzed by the heterodimeric E2 enzyme Ube2N/Ube2V2. Ube2W targets multiple TRIM5α internal lysines with Ub especially lysines 45 and 50, rather than modifying the N-terminal amino group, which is instead αN-acetylated in cells. E2 depletion or Ub mutation inhibits TRIM5α ubiquitination in cells and restores restricted viral reverse transcription, but not infection. Our data indicate that the stepwise formation of anchored Lys63-linked polyUb is a critical early step in the TRIM5α restriction mechanism and identify the E2 Ub-conjugating cofactors involved

Multiplanet systems in inviscid discs can avoid forming resonant chains

ABSTRACT Convergent migration involving multiple planets embedded in a viscous protoplanetary disc is expected to produce a chain of planets in mean motion resonances (MMRs), but the multiplanet systems observed by the Kepler spacecraft are generally not in resonance. We demonstrate that under equivalent conditions, where in a viscous disc convergent migration will form a long-term stable system of planets in a chain of MMRs, migration in an inviscid disc often produces a system which is highly dynamically unstable. In particular, if planets are massive enough to significantly perturb the disc surface density and drive vortex formation, the smooth capture of planets into MMRs is disrupted. As planets pile up in close orbits, not protected by resonances, close encounters increase the probability of planet–planet collisions, even while the gas disc is still present. While inviscid discs often produce unstable non-resonant systems, stable, closely packed, non-resonant systems can also be formed. Thus, when examining the expectation for planet migration to produce planetary systems in MMRs, the effective turbulent viscosity of the protoplanetary disc is a key parameter.</jats:p