Endogenous IL-33 and Its Autoamplification of IL-33/ST2 Pathway Play an Important Role in Asthma.

IL-33 and its receptor ST2 are contributing factors to airway inflammation and asthma exacerbation. The IL-33/ST2 signaling pathway is involved in both the onset and the acute exacerbations of asthma. In this study, we address the role of endogenous IL-33 and its autoamplification of the IL-33/ST2 pathway in Ag-dependent and Ag-independent asthma-like models. Wild-type, IL-33 knockout, ST2 knockout mice were either intratracheally administrated with 500 ng of rIL-33 per day for four consecutive days or were sensitized and challenged with OVA over 21 d. In wild-type mice, IL-33 or OVA induced similar airway hyperresponsiveness and eosinophilic airway inflammation. IL-33 induced its own mRNA and ST2L mRNA expression in the lung. IL-33 autoamplified itself and ST2 protein expression in airway epithelial cells. OVA also induced IL-33 and ST2 protein expression. In IL-33 knockout mice, the IL-33- and OVA-induced airway hyperresponsiveness and eosinophilic airway inflammation were both significantly attenuated, whereas IL-33-induced ST2L mRNA expression was preserved, although no autoamplification of IL-33/ST2 pathway was observed. In ST2 knockout mice, IL-33 and OVA induced airway hyperresponsiveness and eosinophilic airway inflammation were both completely diminished, and no IL-33/ST2 autoamplification was observed. These results suggest that endogenous IL-33 and its autoamplification of IL-33/ST2 pathway play an important role in the induction of asthma-like phenotype. Thus an intact IL-33/ST2 pathway is necessary for both Ag-dependent and Ag-independent asthma-like mouse models

Stratified NH and ND emission in the prestellar core 16293E in L1689N

Context. High degrees of deuterium fractionation are commonly found in cold prestellar cores and in the envelopes around young protostars. As it brings strong constraints to chemical models, deuterium chemistry is often used to infer core history or molecule formation pathways. Whereas a large number of observations are available regarding interstellar deuterated stable molecules, relatively little is known about the deuteration of hydride radicals, as their fundamental rotational transitions are at high frequencies where the atmosphere is mostly opaque. Aims. Nitrogen hydride radicals are important species in nitrogen chemistry, as they are thought to be related to ammonia formation. Observations have shown that ammonia is strongly deuterated, with [NH_2D]/[NH_3] ~ 10%. Models predict similarly high [ND]/[NH] ratios, but so far only one observational determination of this ratio is available, towards the envelope of the protostar IRAS16293-2422. To test model predictions, we aim here to determine [ND]/[NH] in a dense, starless core. Methods. We observed NH and ND in 16293E with the HIFI spectrometer on board the Herschel Space Observatory as part of the CHESS guaranteed time key programme, and derived the abundances of these two species using a non local thermodynamic equilibrium radiative transfer model. Results. Both NH and ND are detected in the source, with ND in emission and NH in absorption against the continuum that arises from the cold dust emission. Our model shows, however, that the ND emission and the NH absorption originate from different layers in the cloud, as further evidenced by their different velocities. In the central region of the core, we can set a lower limit to the [ND]/[NH] ratio of ≳2%. This estimate is consistent with recent pure gas-phase models of nitrogen chemistry

Social networks and labour productivity in Europe: An empirical investigation

This paper uses firm-level data recorded in the AMADEUS database to investigate the distribution of labour productivity in different European countries. We find that the upper tail of the empirical productivity distributions follows a decaying power-law, whose exponent $\alpha$ is obtained by a semi-parametric estimation technique recently developed by Clementi et al. (2006). The emergence of "fat tails" in productivity distribution has already been detected in Di Matteo et al. (2005) and explained by means of a model of social network. Here we show that this model is tested on a broader sample of countries having different patterns of social network structure. These different social attitudes, measured using a social capital indicator, reflect in the power-law exponent estimates, verifying in this way the existence of linkages among firms' productivity performance and social network.Comment: LaTeX2e; 18 pages with 3 figures; Journal of Economic Interaction and Coordination, in pres

Molecular excitation in the Interstellar Medium: recent advances in collisional, radiative and chemical processes

We review the different excitation processes in the interstellar mediumComment: Accepted in Chem. Re

Hydrogen cyanide and isocyanide in prestellar cores

We studied the abundance of HCN, H13CN, and HN13C in a sample of prestellar cores, in order to search for species associated with high density gas. We used the IRAM 30m radiotelescope to observe along the major and the minor axes of L1498, L1521E, and TMC 2, three cores chosen on the basis of their CO depletion properties. We mapped the J=1-0 transition of HCN, H13CN, and HN13C towards the source sample plus the J=1-0 transition of N2H+ and the J=2-1 transition of C18O in TMC 2. We used two different radiative transfer codes, making use of recent collisional rate calculations, in order to determine more accurately the excitation temperature, leading to a more exact evaluation of the column densities and abundances. We find that the optical depths of both H13CN(1-0) and HN13C(1-0) are non-negligible, allowing us to estimate excitation temperatures for these transitions in many positions in the three sources. The observed excitation temperatures are consistent with recent computations of the collisional rates for these species and they correlate with hydrogen column density inferred from dust emission. We conclude that HCN and HNC are relatively abundant in the high density zone, n(H2) about 10^5 cm-3, where CO is depleted. The relative abundance [HNC]/[HCN] differs from unity by at most 30 per cent consistent with chemical expectations. The three hyperfine satellites of HCN(1-0) are optically thick in the regions mapped, but the profiles become increasingly skewed to the blue (L1498 and TMC 2) or red (L1521E) with increasing optical depth suggesting absorption by foreground layers.Comment: 13 pages, 19 figures, to be published in Astronomy and Astrophysic

Estimating time-to-onset of adverse drug reactions from spontaneous reporting databases.

International audienceBACKGROUND: Analyzing time-to-onset of adverse drug reactions from treatment exposure contributes to meeting pharmacovigilance objectives, i.e. identification and prevention. Post-marketing data are available from reporting systems. Times-to-onset from such databases are right-truncated because some patients who were exposed to the drug and who will eventually develop the adverse drug reaction may do it after the time of analysis and thus are not included in the data. Acknowledgment of the developments adapted to right-truncated data is not widespread and these methods have never been used in pharmacovigilance. We assess the use of appropriate methods as well as the consequences of not taking right truncation into account (naïve approach) on parametric maximum likelihood estimation of time-to-onset distribution. METHODS: Both approaches, naïve or taking right truncation into account, were compared with a simulation study. We used twelve scenarios for the exponential distribution and twenty-four for the Weibull and log-logistic distributions. These scenarios are defined by a set of parameters: the parameters of the time-to-onset distribution, the probability of this distribution falling within an observable values interval and the sample size. An application to reported lymphoma after anti TNF-¿ treatment from the French pharmacovigilance is presented. RESULTS: The simulation study shows that the bias and the mean squared error might in some instances be unacceptably large when right truncation is not considered while the truncation-based estimator shows always better and often satisfactory performances and the gap may be large. For the real dataset, the estimated expected time-to-onset leads to a minimum difference of 58 weeks between both approaches, which is not negligible. This difference is obtained for the Weibull model, under which the estimated probability of this distribution falling within an observable values interval is not far from 1. CONCLUSIONS: It is necessary to take right truncation into account for estimating time-to-onset of adverse drug reactions from spontaneous reporting databases

Design of experiments to study the impact of process parameters on droplet size and development of non-invasive imaging techniques in tablet coating

Atomisation of an aqueous solution for tablet film coating is a complex process with multiple factors determining droplet formation and properties. The importance of droplet size for an efficient process and a high quality final product has been noted in the literature, with smaller droplets reported to produce smoother, more homogenous coatings whilst simultaneously avoiding the risk of damage through over-wetting of the tablet core. In this work the effect of droplet size on tablet film coat characteristics was investigated using X-ray microcomputed tomography (XμCT) and confocal laser scanning microscopy (CLSM). A quality by design approach utilising design of experiments (DOE) was used to optimise the conditions necessary for production of droplets at a small (20 μm) and large (70 μm) droplet size. Droplet size distribution was measured using real-time laser diffraction and the volume median diameter taken as a response. DOE yielded information on the relationship three critical process parameters: pump rate, atomisation pressure and coating-polymer concentration, had upon droplet size. The model generated was robust, scoring highly for model fit (R2 = 0.977), predictability (Q2 = 0.837), validity and reproducibility. Modelling confirmed that all parameters had either a linear or quadratic effect on droplet size and revealed an interaction between pump rate and atomisation pressure. Fluidised bed coating of tablet cores was performed with either small or large droplets followed by CLSM and XμCT imaging. Addition of commonly used contrast materials to the coating solution improved visualisation of the coating by XμCT, showing the coat as a discrete section of the overall tablet. Imaging provided qualitative and quantitative evidence revealing that smaller droplets formed thinner, more uniform and less porous film coats