Covariant One-Loop Amplitudes in D=11

We generalize to the eleven-dimensional superparticle Berkovits' prescription for loop computations in the pure spinor approach to covariant quantization of the superstring. Using these ten- and eleven-dimensional results, we compute covariantly the following one-loop amplitudes: C\wedge X_8 in M-theory; B\wedge X_8 in type II string theory and F^4 in type I. We also verify the consistency of the formalism in eleven dimensions by recovering the correct classical action from tree-level amplitudes. As the superparticle is only a first approximation to the supermembrane, we comment on the possibility of extending this construction to the latter. Finally, we elaborate on the relationship between the present BRST language and the spinorial cohomology approach to corrections of the effective action.Comment: 41 pages; minor corrections, journal versio

Super D-branes from BRST Symmetry

Recently a new formalism has been developed for the covariant quantization of superstrings. We study properties of Dp-branes and p-branes in this new framework, focusing on two different topics: effective actions and boundary states for Dp-branes. We present a derivation of the Wess-Zumino terms for super (D)p-branes using BRST symmetry. To achieve this we derive the BRST symmetry for superbranes, starting from the approach with/without pure spinors, and completely characterize the WZ terms as elements of the BRST cohomology. We also develope the boundary state description of Dp-branes by analyzing the boundary conditions for open strings in the completely covariant (i.e., without pure spinors) BRST formulation.Comment: 31 pp; journal version, expended discussion of D-brane pure spinor constraints in Section 2.

A rotating white dwarf shows different compositions on its opposite faces

White dwarfs, the extremely dense remnants left behind by most stars after their death, are characterised by a mass comparable to that of the Sun compressed into the size of an Earth-like planet. In the resulting strong gravity, heavy elements sink toward the centre and the upper layer of the atmosphere contains only the lightest element present, usually hydrogen or helium. Several mechanisms compete with gravitational settling to change a white dwarf's surface composition as it cools, and the fraction of white dwarfs with helium atmospheres is known to increase by a factor ~2.5 below a temperature of about 30,000 K; therefore, some white dwarfs that appear to have hydrogen-dominated atmospheres above 30,000 K are bound to transition to be helium-dominated as they cool below it. Here we report observations of ZTF J203349.8+322901.1, a transitioning white dwarf with two faces: one side of its atmosphere is dominated by hydrogen and the other one by helium. This peculiar nature is likely caused by the presence of a small magnetic field, which creates an inhomogeneity in temperature, pressure or mixing strength over the surface. ZTF J203349.8+322901.1 might be the most extreme member of a class of magnetic, transitioning white dwarfs -- together with GD 323, a white dwarf that shows similar but much more subtle variations. This new class could help shed light on the physical mechanisms behind white dwarf spectral evolution.Comment: 45 pages, 11 figure

Mathematical Modelling of DNA Replication Reveals a Trade-off between Coherence of Origin Activation and Robustness against Rereplication

Eukaryotic genomes are duplicated from multiple replication origins exactly once per cell cycle. In Saccharomyces cerevisiae, a complex molecular network has been identified that governs the assembly of the replication machinery. Here we develop a mathematical model that links the dynamics of this network to its performance in terms of rate and coherence of origin activation events, number of activated origins, the resulting distribution of replicon sizes and robustness against DNA rereplication. To parameterize the model, we use measured protein expression data and systematically generate kinetic parameter sets by optimizing the coherence of origin firing. While randomly parameterized networks yield unrealistically slow kinetics of replication initiation, networks with optimized parameters account for the experimentally observed distribution of origin firing times. Efficient inhibition of DNA rereplication emerges as a constraint that limits the rate at which replication can be initiated. In addition to the separation between origin licensing and firing, a time delay between the activation of S phase cyclin-dependent kinase (S-Cdk) and the initiation of DNA replication is required for preventing rereplication. Our analysis suggests that distributive multisite phosphorylation of the S-Cdk targets Sld2 and Sld3 can generate both a robust time delay and contribute to switch-like, coherent activation of replication origins. The proposed catalytic function of the complex formed by Dpb11, Sld3 and Sld2 strongly enhances coherence and robustness of origin firing. The model rationalizes how experimentally observed inefficient replication from fewer origins is caused by premature activation of S-Cdk, while premature activity of the S-Cdk targets Sld2 and Sld3 results in DNA rereplication. Thus the model demonstrates how kinetic deregulation of the molecular network governing DNA replication may result in genomic instability

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Online on the mobile: Internet use on smartphones and associated risks among youth in Europe

1. This report analyses how children aged 9-16 changed their internet use between 2010, when most children used fixed computers and laptops, and 2013, with over one-quarter (c. 28%) of 9-12 year olds, and three-fifths (c. 60%) of 13-16 year olds, accessing the internet via a smartphone. 2. Children experience slightly increased risk when accessing the internet via a smartphone or tablet. Historically, such children came from richer, more privileged backgrounds, and spent more time online: all linked with risk exposure. Now that most 13-16 year olds have smartphones, they are no longer an elite. Along with extra risk, children with smartphones access the internet more often, engage in a greater range of activities, and have a higher number of skills. 3. The likelihood of children experiencing three or more risks has not changed greatly between 2010 and 2013, except for a rise in the 9-10 age group (from 1% on 2010 to 4% in 2013), and a rise among girls (14% in 2010, 17% in 2013). Among 9-10s, 19% encountered one or more risks online in 2010, while this rose to 24% in 2013. 4. While younger children are less likely than older children to encounter online risks, they are more likely to be affected by the risks they experience. Parents of younger children with smartphones should be encouraged to actively regulate their child’s internet use. The younger the child, the more their parents should involve themselves. 5. For six of the seven risks investigated in 2010 and 2013, the proportion of children experiencing the risk has risen. Fewer children (aged 11-16) had received sexual messages: this had declined from 14% in 2010 to 11% in 2013. 6. 2010 data indicate that parents whose children had smart handheld devices were less likely to lay down rules around their child’s internet activities. Although this group of children were comparatively privileged, and older, and more likely to encounter risk, parents seem to have trusted their child to make good choices. Given that mobile internet access is associated with fewer parental restrictions, this 2010 data raises concern in 2013, now that so many more children have smartphones. 7. In 2010, parents of children with smart handheld devices were also less likely to use technology filters to keep their child safe. This may reflect the difficulties parents experienced in finding consistent, easy-to-use, handset controls to support their child’s safe mobile internet use. In 2013, many more parents are allowing children to use smartphones, but we do not know much about their strategies for keeping children safe. 8. Children’s risk experiences vary with gender and age, and this is clear from both the 2010 and the 2013 data. Smart media introduce new risks such as geo-locational data and apps which connect mobile users with co-present strangers. Such risks to children’s safety have yet to be investigated. 9. National differences are important but the overall picture is one of “more and more”: more access, more often, using more devices, with more risk. As Livingstone et al say (2011: 142) “children’s experiences of online opportunities and risks go hand in hand – the more of one tends to mean the more of the other”. Major recommendations 1. Industry stakeholders – software developers, technology companies, service providers – should prioritise the development of a suite of consistent, easy-to-use, handset controls which parents can use to support and monitor their children’s safe mobile internet use. 2. Smartphones pose new risks for children, requiring new research