Reassessment of tritium content in CFC tiles exposed to the JET D-T campaign in 1997

In 2019 two MkIIA divertor tiles (6IN3 and 4BN4) exposed during DTE1 were retrieved at CCFE for Thermal Desorption Spectroscopy (TDS) and pyrolysis analyses. A set of samples were prepared using a coring technique. The highest tritium (T) inventories were found in the shadowed corner of the inner divertor due to asymmetric deposition. TDS analyses indicated that T is desorbed at rather high temperatures with maximum release peaks at ∼590 and 820 °C. A few samples were reannealed at 850 °C using the same heating procedure and it turned out that a further ∼40–50 % of T was still released indicating that the annealing procedure used does not empty the sample completely. Pyrolysis results for thin disks cut from the surface of the tile were somewhat higher than the corresponding TDS results. T amounts were also investigated as a function of depth from the tile surface up to a depth of ∼4.5 mm and T was detected at these depths. Comparison was also made with old results obtained with the pyrolysis technique and a PIN-diode method a few years after the DTE1 experiment, allowing for the natural decay and off-gassing of T. Our results agree within a factor of ∼3 with these results

Local lung hypoxia determines epithelial fate decisions during alveolar regeneration.

After influenza infection, lineage-negative epithelial progenitors (LNEPs) exhibit a binary response to reconstitute epithelial barriers: activating a Notch-dependent ΔNp63/cytokeratin 5 (Krt5) remodelling program or differentiating into alveolar type II cells (AEC2s). Here we show that local lung hypoxia, through hypoxia-inducible factor (HIF1α), drives Notch signalling and Krt5pos basal-like cell expansion. Single-cell transcriptional profiling of human AEC2s from fibrotic lungs revealed a hypoxic subpopulation with activated Notch, suppressed surfactant protein C (SPC), and transdifferentiation toward a Krt5pos basal-like state. Activated murine Krt5pos LNEPs and diseased human AEC2s upregulate strikingly similar core pathways underlying migration and squamous metaplasia. While robust, HIF1α-driven metaplasia is ultimately inferior to AEC2 reconstitution in restoring normal lung function. HIF1α deletion or enhanced Wnt/β-catenin activity in Sox2pos LNEPs blocks Notch and Krt5 activation, instead promoting rapid AEC2 differentiation and migration and improving the quality of alveolar repair

A habituation account of change detection in same/different judgments

We investigated the basis of change detection in a short-term priming task. In two experiments, participants were asked to indicate whether or not a target word was the same as a previously presented cue. Data from an experiment measuring magnetoencephalography failed to find different patterns for “same” and “different” responses, consistent with the claim that both arise from a common neural source, with response magnitude defining the difference between immediate novelty versus familiarity. In a behavioral experiment, we tested and confirmed the predictions of a habituation account of these judgments by comparing conditions in which the target, the cue, or neither was primed by its presentation in the previous trial. As predicted, cue-primed trials had faster response times, and target-primed trials had slower response times relative to the neither-primed baseline. These results were obtained irrespective of response repetition and stimulus–response contingencies. The behavioral and brain activity data support the view that detection of change drives performance in these tasks and that the underlying mechanism is neuronal habituation

Design and implementation of the START (STem cells for ARDS Treatment) trial, a phase 1/2 trial of human mesenchymal stem/stromal cells for the treatment of moderate-severe acute respiratory distress syndrome

Background: Despite advances in supportive care, moderate-severe acute respiratory distress syndrome (ARDS) is associated with high mortality rates, and novel therapies to treat this condition are needed. Compelling pre-clinical data from mouse, rat, sheep and ex vivo perfused human lung models support the use of human mesenchymal stem (stromal) cells (MSCs) as a novel intravenous therapy for the early treatment of ARDS. Methods: This article describes the study design and challenges encountered during the implementation and phase 1 component of the START (STem cells for ARDS Treatment) trial, a phase 1/2 trial of bone marrow-derived human MSCs for moderate-severe ARDS. A trial enrolling 69 subjects is planned (9 subjects in phase 1, 60 subjects in phase 2 treated with MSCs or placebo in a 2:1 ratio). Results: This report describes study design features that are unique to a phase 1 trial in critically ill subjects and the specific challenges of implementation of a cell-based therapy trial in the ICU. Conclusions: Experience gained during the design and implementation of the START study will be useful to investigators planning future phase 1 clinical trials based in the ICU, as well as trials of cell-based therapy for other acute illnesses. Trial registration Clinical Trials Registration: NCT01775774 and NCT02097641

Reelin Controls Progenitor Cell Migration in the Healthy and Pathological Adult Mouse Brain

Understanding the signals that control migration of neural progenitor cells in the adult brain may provide new therapeutic opportunities. Reelin is best known for its role in regulating cell migration during brain development, but we now demonstrate a novel function for reelin in the injured adult brain. First, we show that Reelin is upregulated around lesions. Second, experimentally increasing Reelin expression levels in healthy mouse brain leads to a change in the migratory behavior of subventricular zone-derived progenitors, triggering them to leave the rostral migratory stream (RMS) to which they are normally restricted during their migration to the olfactory bulb. Third, we reveal that Reelin increases endogenous progenitor cell dispersal in periventricular structures independently of any chemoattraction but via cell detachment and chemokinetic action, and thereby potentiates spontaneous cell recruitment to demyelination lesions in the corpus callosum. Conversely, animals lacking Reelin signaling exhibit reduced endogenous progenitor recruitment at the lesion site. Altogether, these results demonstrate that beyond its known role during brain development, Reelin is a key player in post-lesional cell migration in the adult brain. Finally our findings provide proof of concept that allowing progenitors to escape from the RMS is a potential therapeutic approach to promote myelin repair

Familiarization: A theory of repetition suppression predicts interference between overlapping cortical representations

Repetition suppression refers to a reduction in the cortical response to a novel stimulus that results from repeated presentation of the stimulus. We demonstrate repetition suppression in a well established computational model of cortical plasticity, according to which the relative strengths of lateral inhibitory interactions are modified by Hebbian learning. We present the model as an extension to the traditional account of repetition suppression offered by sharpening theory, which emphasises the contribution of afferent plasticity, by instead attributing the effect primarily to plasticity of intra-cortical circuitry. In support, repetition suppression is shown to emerge in simulations with plasticity enabled only in intra-cortical connections. We show in simulation how an extended ‘inhibitory sharpening theory’ can explain the disruption of repetition suppression reported in studies that include an intermediate phase of exposure to additional novel stimuli composed of features similar to those of the original stimulus. The model suggests a re-interpretation of repetition suppression as a manifestation of the process by which an initially distributed representation of a novel object becomes a more localist representation. Thus, inhibitory sharpening may constitute a more general process by which representation emerges from cortical re-organisation

Urban resilience:two diverging interpretations

This paper uses two diverging interpretations of resilience to review and assess current UK policies for urban resilience. Both developed in scientific studies, the first interpretation is based on a mechanistic model of systems that can recover their original state after shocks, and the second is based on an evolutionary model enabling adaptation to disturbances. The literature review demonstrates that at present urban resilience is predominantly associated with the former. By contrast, only few policies and studies are inspired by the latter, although this is better suited to analyse dynamics of urban adaptation and manage cities accordingly. The contribution of this paper to an understanding of urban resilience is therefore twofold. First, an identification of the long-term consequences on the built environment associated with each model is provided, with the mechanical model ultimately hindering adaptation. Second, some approaches to generate effective responses to environmental and societal change are identified. Ultimately, this paper emphasises that the idea of a resilient city is fit for this age characterised by uncertainty, albeit it requires the recognition within planning practice that urban adaptation cannot be attained with current methodologies, and that much can be learned from theories on the resilience of ecosystems.

Face scanning and spontaneous emotion preference in Cornelia de Lange syndrome and Rubinstein-Taybi syndrome

Background Existing literature suggests differences in face scanning in individuals with different socio-behavioural characteristics. Cornelia de Lange syndrome (CdLS) and Rubinstein-Taybi syndrome (RTS) are two genetically defined neurodevelopmental disorders with unique profiles of social behaviour. Methods Here, we examine eye gaze to the eye and mouth regions of neutrally expressive faces, as well as the spontaneous visual preference for happy and disgusted facial expressions compared to neutral faces, in individuals with CdLS versus RTS. Results Results indicate that the amount of time spent looking at the eye and mouth regions of faces was similar in 15 individuals with CdLS and 17 individuals with RTS. Both participant groups also showed a similar pattern of spontaneous visual preference for emotions. Conclusions These results provide insight into two rare, genetically defined neurodevelopmental disorders that have been reported to exhibit contrasting socio-behavioural characteristics and suggest that differences in social behaviour may not be sufficient to predict attention to the eye region of faces. These results also suggest that differences in the social behaviours of these two groups may be cognitively mediated rather than subcortically mediated

A large-scale study on the effects of sex on gray matter asymmetry

Research on sex-related brain asymmetries has not yielded consistent results. Despite its importance to further understanding of normal brain development and mental disorders, the field remains relatively unexplored. Here we employ a recently developed asymmetry measure, based on the Dice coefficient, to detect sex-related gray matter asymmetries in a sample of 457 healthy participants (266 men and 191 women) obtained from 5 independent databases. Results show that women’s brains are more globally symmetric than men’s (p < 0.001). Although the new measure accounts for asymmetries distributed all over the brain, several specific structures were identified as systematically more symmetric in women, such as the thalamus and the cerebellum, among other structures, some of which are typically involved in language production. These sex-related asymmetry differences may be defined at the neurodevelopmental stage and could be associated with functional and cognitive sex differences, as well as with proneness to develop a mental disorder