Heterogeneity in thymic emigrants: implications for thymectomy and immunosenescence.

The development of mature, antigen-inexperienced (naive) T cells begins in the thymus and continues after export into the periphery. Post-thymic maturation of naive T cells, in humans, coincides with the progressive loss of markers such as protein tyrosine kinase 7 (PTK7) and platelet endothelial cell adhesion molecule-1 (CD31). As a consequence, subpopulations of naive T cells can be recognised raising questions about the processes that give rise to the loss of these markers and their exact relationship to recent thymic emigrants (RTE). Here, we combine a mathematical survival analysis approach and data from healthy and thymectomised humans to understand the apparent persistence of populations of 'veteran' PTK7 (+) T cells in thymectomised individuals. We show that a model of heterogeneity in rates of maturation, possibly linked to natural variation in TCR signalling thresholds or affinity for self-antigens, can explain the data. This model of maturation predicts that the average post-thymic age of PTK7 (+) T cells will increase linearly with the age of the host suggesting that, despite the immature phenotype, PTK7 (+) cells do not necessarily represent a population of RTE. Further, the model predicts an accelerated increase in the average post-thymic age of residual PTK7 (+) T cells following thymectomy and may also explain in part the prematurely aged phenotype of the naive T cell pool in individuals thymectomised early in life

Detection of SiO emission from a massive dense cold core

We report the detection of the SiO (J = 2 - 1) transition from the massive cold dense core G333.125-0.562. The core remains undetected at wavelengths shorter than 70 micron and has compact 1.2 mm dust continuum. The SiO emission is localised to the core. The observations are part of a continuing multi-molecular line survey of the giant molecular cloud G333. Other detected molecules in the core include 13CO, C18O, CS, HCO+, HCN, HNC, CH3OH, N2H+, SO, HC3N, NH3, and some of their isotopes. In addition, from NH3 (1,1) and (2,2) inversion lines, we obtain a temperature of 13 K. From fitting to the spectral energy distribution we obtain a colour temperature of 18 K and a gas mass of 2 x 10^3 solar mass. We have also detected a 22 GHz water maser in the core, together with methanol maser emission, suggesting the core will host massive star formation. We hypothesise that the SiO emission arises from shocks associated with an outflow in the cold core.Comment: 6 pages, 4 figures, 1 table, to be published in MNRA

British policy in relation to Portuguese claims in West Africa 1876 to 1884

The period 1876 to 1884 lies between the time when European Governments showed but slight interest in Africa and the years of the 'Scramble' for that continent. It saw the work of the International Association, financed by the King of the Belgians, the explorations of de Brazza towards the Congo from the French colony of Gaboon and the realisation by Bismarck of the far-reaching issues involved in the Congo Question. As British Ambassador in Portugal from 1876 to l88l, Robert Morier strongly urged the settlement of all questions in dispute between Great Britain and Portugal overseas and the establishment of increased British influence in Africa, both directly and indirectly through Portugal. That country claimed rights of sovereignty on the West Coast of Africa from 5&deg;12' to 8&deg; South latitude but, largely because of the prevalence of the Slave Trade in Portuguese possessions, Great Britain had refused to recognise these claims. Morier's attempts to bring about a reversal of this decision failed but the French advance towards the Congo caused the British Government to change its attitude. After the ratification, in November 1882, by the French Government of the Treaty signed by de Brazza with the native chief on Stanley Pool, Great Britain re-opened negotiations with Portugal on the bases of the recognition by her of the traditional claims of Portugal and the opening, on certain conditions, of Portuguese colonies to the trade of all nations. After long and tedious negotiations the Congo Treaty was finally signed on 26 February 1884 by representatives of Great Britain and Portugal. As a result of the refusal of Germany and of France to recognise its terms, the Treaty remained unratified but, in its place, a wider settlement of African questions was worked out at the Berlin Conference, November 1884 to February 1885. Great Britain's policy of opening up to the trade of all nations hitherto closed areas in Africa was accepted but not her exclusive attitude of settling by herself questions which affected other European nations.<p

Sub-au imaging of water vapour clouds around four Asymptotic Giant Branch stars

We present MERLIN maps of the 22-GHz H2O masers around four low-mass late-type stars (IK Tau U Ori, RT Vir and U Her), made with an angular resolution of ~ 15 milliarcsec and a velocity resolution of 0.1 km s-1. The H2O masers are found in thick expanding shells with inner radii ~ 6 to 16 au and outer radii four times larger. The expansion velocity increases radially through the H2O maser regions, with logarithmic velocity gradients of 0.5--0.9. IK Tau and RT Vir have well-filled H2O maser shells with a spatial offset between the near and far sides of the shell, which suggests that the masers are distributed in oblate spheroids inclined to the line of sight. U Ori and U Her have elongated poorly-filled shells with indications that the masers at the inner edge have been compressed by shocks; these stars also show OH maser flares. MERLIN resolves individual maser clouds, which have diameters of 2 -- 4 au and filling factors of only ~ 0.01 with respect to the whole H2O maser shells. The CSE velocity structure gives additional evidence the maser clouds are density bounded. Masing clouds can be identified over a similar timescale to their sound crossing time (~2 yr) but not longer. The sizes and observed lifetimes of these clouds are an order of magnitude smaller than those around red supergiants, similar to the ratio of low-mass:high-mass stellar masses and sizes. This suggests that cloud size is determined by stellar properties, not local physical phenomena in the wind.Comment: 21 pages, including 14 figures and 8 tables. Accepted for publication in MNRA

Iridium-Catalyzed Enantioselective Hydrogenation of Vinylsilanes

We have screened a diverse array of iridium complexes derived from chiral N,P ligands as catalysts for the asymmetric hydrogenation of vinylsilanes, a transformation for which generally applicable catalysts were lacking. Several catalysts emerged from this study that enabled the highly enantioselective hydrogenation of a wide range of vinylsilanes with trisubstituted or disubstituted terminal C=C bonds bearing aryl, alkyl, ethoxycarbonyl, or hydroxymethyl substituents. In addition to trimethylsilyl and dimethyl(phenyl) silyl derivatives, trialkoxysilyl- and silacyclobutyl-substituted alkenes were used as substrates

Observations and radiative transfer modelling of a massive dense cold core in G333

Cold massive cores are one of the earliest manifestations of high mass star formation. Following the detection of SiO emission from G333.125-0.562, a cold massive core, further investigations of the physics, chemistry and dynamics of this object has been carried out. Mopra and NANTEN2 molecular line profile observations, Australia Telescope Compact Array (ATCA) line and continuum emission maps, and Spitzer 24 and 70 \mum images were obtained. These new data further constrain the properties of this prime example of the very early stages of high mass star formation. A model for the source was constructed and compared directly with the molecular line data using a 3D molecular line transfer code - MOLLIE. The ATCA data reveal that G333.125-0.562 is composed of two sources. One of the sources is responsible for the previously detected molecular outflow and is detected in the Spitzer 24 and 70 \mum band data. Turbulent velocity widths are lower than other more active regions of G333 which reflects the younger evolutionary stage and/or lower mass of this core. The molecular line modelling requires abundances of the CO isotopes that strongly imply heavy depletion due to freeze-out of this species onto dust grains. The principal cloud is cold, moderately turbulent and possesses an outflow which indicates the presence of a central driving source. The secondary source could be an even less evolved object as no apparent associations with continuum emissions at (far-)infrared wavelengths.Comment: 10 pages, accepted to MNRA

Of mice and mates:Automated classification and modelling of mouse behaviour in groups using a single model across cages

Behavioural experiments often happen in specialised arenas, but this may confound the analysis. To address this issue, we provide tools to study mice in the home-cage environment, equipping biologists with the possibility to capture the temporal aspect of the individual’s behaviour and model the interaction and interdependence between cage-mates with minimal human intervention. Our main contribution is the novel Global Behaviour Model (GBM) which summarises the joint behaviour of groups of mice across cages, using a permutation matrix to match the mouse identities in each cage to the model. In support of the above, we also (a) developed the Activity Labelling Module (ALM) to automatically classify mouse behaviour from video, and (b) released two datasets, ABODe for training behaviour classifiers and IMADGE for modelling behaviour

Dual-stream spatiotemporal networks with feature sharing for monitoring animals in the home cage

This paper presents a spatiotemporal deep learning approach for mouse behavioural classification in the home-cage. Using a series of dual-stream architectures with assorted modifications to increase performance, we introduce a novel feature sharing approach that jointly processes the streams at regular intervals throughout the network. To investigate the efficacy of this approach, models were evaluated by dissociating the streams and training/testing in the same rigorous manner as the main classifiers. Using an annotated, publicly available dataset of a singly-housed mice, we achieve prediction accuracy of 86.47% using an ensemble of a Inception-based network and an attention-based network, both of which utilize this feature sharing. We also demonstrate through ablation studies that for all models, the feature-sharing architectures consistently perform better than conventional ones having separate streams. The best performing models were further evaluated on other activity datasets, both mouse and human. Future work will investigate the effectiveness of feature sharing to behavioural classification in the unsupervised anomaly detection domain

Interleukin 7 from Maternal Milk Crosses the Intestinal Barrier and Modulates T- Cell Development in Offspring

Background Breastfeeding protects against illnesses and death in hazardous environments, an effect partly mediated by improved immune function. One hypothesis suggests that factors within milk supplement the inadequate immune response of the offspring, but this has not been able to account for a series of observations showing that factors within maternally derived milk may supplement the development of the immune system through a direct effect on the primary lymphoid organs. In a previous human study we reported evidence suggesting a link between IL-7 in breast milk and the thymic output of infants. Here we report evidence in mice of direct action of maternally-derived IL-7 on T cell development in the offspring. Methods and Findings  We have used recombinant IL-7 labelled with a fluorescent dye to trace the movement in live mice of IL-7 from the stomach across the gut and into the lymphoid tissues. To validate the functional ability of maternally derived IL- 7 we cross fostered IL-7 knock-out mice onto normal wild type mothers. Subsets of thymocytes and populations of peripheral T cells were significantly higher than those found in knock-out mice receiving milk from IL-7 knock-out mothers. Conclusions/Significance Our study provides direct evidence that interleukin 7, a factor which is critical in the development of T lymphocytes, when maternally derived can transfer across the intestine of the offspring, increase T cell production in the thymus and support the survival of T cells in the peripheral secondary lymphoid tissue

Extrapleural pneumonectomy versus pleurectomy/decortication in the surgical management of malignant pleural mesothelioma: Results in 663 patients

ObjectiveThe optimal procedure for resection of malignant pleural mesothelioma is controversial, partly because previous analyses include small numbers of patients. We performed a multi-institutional study to increase statistical power to detect significant differences in outcome between extrapleural pneumonectomy and pleurectomy/decortication.MethodsPatients with malignant pleural mesothelioma who underwent extrapleural pneumonectomy or pleurectomy/decortication at 3 institutions were identified. Survival and prognostic factors were analyzed by the Kaplan–Meier method, log-rank test, and Cox proportional hazards analysis.ResultsFrom 1990 to 2006, 663 consecutive patients (538 men and 125 women) underwent resection. The median age was 63 years (range, 26–93 years). The operative mortality was 7% for extrapleural pneumonectomy (n = 27/385) and 4% for pleurectomy/decortication (n = 13/278). Significant survival differences were seen for American Joint Committee on Cancer stages 1 to 4 (P < .001), epithelioid versus non-epithelioid histology (P < .001), extrapleural pneumonectomy versus pleurectomy/decortication (P < .001), multimodality therapy versus surgery alone (P < .001), and gender (P < .001). Multivariate analysis demonstrated a hazard rate of 1.4 for extrapleural pneumonectomy (P < .001) controlling for stage, histology, gender, and multimodality therapy.ConclusionPatients who underwent pleurectomy/decortication had a better survival than those who underwent extrapleural pneumonectomy; however, the reasons are multifactorial and subject to selection bias. At present, the choice of resection should be tailored to the extent of disease, patient comorbidities, and type of multimodality therapy planned