Pavlovian influences on learning differ between rats and mice in a counter-balanced Go/NoGo judgement bias task

Judgement bias tests of animal affect and hence welfare assume that the animal's responses to ambiguous stimuli, which may herald positive or negative outcomes, are under instrumental control and reflect 'optimism' or 'pessimism' about what will happen. However, Pavlovian control favours responses (e.g. approach or withdrawal) according to the valence associated with a stimulus, rather than the anticipated response outcomes. Typically, positive contexts promote action and approach whilst negative contexts promote inhibition or withdrawal. The prevalence of Go-for-reward (Go-pos) and NoGo-to-avoid-punishment (NoGo-neg) judgement bias tasks reflects this Pavlovian influence. A Pavlovian increase or decrease in activity or vigour has also been argued to accompany positive or negative affective states, and this may interfere with instrumental Go or NoGo decisions under ambiguity based on anticipated decision outcomes. One approach to these issues is to develop counter-balanced Go-pos/NoGo-neg and Go-neg/NoGo-pos tasks. Here we implement such tasks in Sprague Dawley rats and C57BL/6J mice using food and air-puff as decision outcomes. We find striking species/strain differences with rats achieving criterion performance on the Go-pos/NoGo-neg task but failing to learn the Go-neg/NoGo-pos task, in line with predictions, whilst mice do exactly the opposite. Pavlovian predispositions may thus differ between species, for example reflecting foraging and predation ecology and/or baseline activity rates. Learning failures are restricted to cues predicting a negative outcome; use of a more powerful air-puff stimulus may thus allow implementation of a fully counter-balanced task. Rats and mice achieve criterion faster than in comparable automated tasks and also show the expected generalisation of responses across ambiguous tones. A fully counter-balanced task thus offers a potentially rapidly implemented and automated method for assessing animal welfare, identifying welfare problems and areas for welfare improvement and 3Rs Refinement, and assessing the effectiveness of refinements

Pulsar-wind nebulae and magnetar outflows: observations at radio, X-ray, and gamma-ray wavelengths

We review observations of several classes of neutron-star-powered outflows: pulsar-wind nebulae (PWNe) inside shell supernova remnants (SNRs), PWNe interacting directly with interstellar medium (ISM), and magnetar-powered outflows. We describe radio, X-ray, and gamma-ray observations of PWNe, focusing first on integrated spectral-energy distributions (SEDs) and global spectral properties. High-resolution X-ray imaging of PWNe shows a bewildering array of morphologies, with jets, trails, and other structures. Several of the 23 so far identified magnetars show evidence for continuous or sporadic emission of material, sometimes associated with giant flares, and a few possible "magnetar-wind nebulae" have been recently identified.Comment: 61 pages, 44 figures (reduced in quality for size reasons). Published in Space Science Reviews, "Jets and Winds in Pulsar Wind Nebulae, Gamma-ray Bursts and Blazars: Physics of Extreme Energy Release

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Impressions of conformity and fantasies of difference Conflicts in the domestic art and architecture of the Roman Empire

SIGLEAvailable from British Library Document Supply Centre-DSC:DXN021653 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Microstructural Evolution by Continuous Recrystallization in a Superplastic Al-Mg Alloy

The boundary misorientations in an Al-1OMg-O.1Zr (wt%) alloy, thermomechanically processed by rolling at 573 K (300°C), were determined both in annealed and in superplastically deformed conditions. A high initial dislocation density in as-rolled material, which obscured any underlying structure, rapidly transformed into a well-defined structure containing boundaries. After annealing for 600 s at 573K, boundaries with misorientations of 1–5° were observed. With further annealing (3000 s), misorientations did not change appreciably and were measured to be 2–7°. Such time represents that necessary to equilibrate at 573K prior to tension testing at that temperature. The material exhibits superplasticity from the onset of deformation and after 100% strain, misorientations were observed to increase to 20–30°. It was concluded that boundaries of such initial misorientations can support superplastic deformation mechanisms including grain boundary sliding.U.S. Naval Air Systems CommandUniversity of Illinoi

An EBSP investigation of alternate microstructures for superplasticity in aluminum-magnesium alloys

The article of record as published may be found at http://dx.doi.org/101016/S1359-6462(96)00403-4This study proposes to provide insight into alternative grain boundary structures in two aluminum-magnesium alloys processed to achieve superplastic behavior. A commercially processes superplastic 5083 aluminum alloy, SKY5083, and a laboratory processed, non-commercial superplastic Al-10Mg-0.1Zr alloy have been selected for examination. Although alloy content, processing routes, and deformation conditions vary for each material, a comparison of results may provide evidence that alternate grain structures and boundary misorientation distributions may support superplasticity in the GBS regime, depending on the TMP processing and alloy system chosen

GRAIN REFINEMENT AND SUPERPLASTICITY IN A LITHIUM-CONTAINING Al-Mg ALLOY BY THERMOMECHANICAL PROCESSING

The refined microstructures and superplastic properties resulting from controlled thermomechanical processing of an Al-8Mg-0.5Li-0.23Zr alloy were evaluated. Rolling between the solvus temperatures for Mg and Li in the alloy allowed for grain refinement by precipitation of β (Al8Mg5) during deformation and subsequent precipitation of δ' (Al3Li) on cooling. Increasing the rolling strain enhance the superplastic ductility of the alloy at 573K in the strain-rate regime of 10-3-10-2 S-1. Elongations in excess of 500 pct. , without cavitation, and a corresponding strain-rate sensitivity coefficient of approximately 0.5, were obtained. TEM investigations of the microstructural characteristics responsible for the mechanical behavior revealed that a more uniformly refined grain structure (3-5µm) evolved by continuous recrystallization (CRX) in material experiencing the larger rolling strain