1,063 research outputs found

    Impacts of the Madden-Julian oscillation on Australian rainfall and circulation

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    Impacts of the MaddenÂżJulian oscillation (MJO) on Australian rainfall and circulation are examined during all four seasons. The authors examine circulation anomalies and a number of different rainfall metrics, each composited contemporaneously for eight MJO phases derived from the real-time multivariate MJO index. Multiple rainfall metrics are examined to allow for greater relevance of the information for applications. The greatest rainfall impact of the MJO occurs in northern Australia in (austral) summer, although in every season rainfall impacts of various magnitude are found in most locations, associated with corresponding circulation anomalies. In northern Australia in all seasons except winter, the rainfall impact is explained by the direct influence of the MJO's tropical convective anomalies, while in winter a weaker and more localized signal in northern Australia appears to result from the modulation of the trade winds as they impinge upon the eastern coasts, especially in the northeast. In extratropical Australia, on the other hand, the occurrence of enhanced (suppressed) rainfall appears to result from induced upward (downward) motion within remotely forced extratropical lows (highs), and from anomalous low-level northerly (southerly) winds that transport moisture from the tropics. Induction of extratropical rainfall anomalies by remotely forced lows and highs appears to operate mostly in winter, whereas anomalous meridional moisture transport appears to operate mainly in the summer, autumn, and to some extent in the sprin

    Differential Interleukin-2 Transcription Kinetics Render Mouse but Not Human T Cells Vulnerable to Splicing Inhibition Early after Activation

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    T cells are nodal players in the adaptive immune response against pathogens and malignant cells. Alternative splicing plays a crucial role in T cell activation, which is analyzed mainly at later time points upon stimulation. Here we have discovered a 2-h time window early after stimulation where optimal splicing efficiency or, more generally, gene expression efficiency is crucial for successful T cell activation. Reducing the splicing efficiency at 4 to 6 h poststimulation significantly impaired murine T cell activation, which was dependent on the expression dynamics of the Egr1-Nab2-interleukin-2 (IL-2) pathway. This time window overlaps the time of peak IL-2 de novo transcription, which, we suggest, represents a permissive time window in which decreased splicing (or transcription) efficiency reduces mature IL-2 production, thereby hampering murine T cell activation. Notably, the distinct expression kinetics of the Egr1-Nab2-IL-2 pathway between mouse and human render human T cells refractory to this vulnerability. We propose that the rational temporal modulation of splicing or transcription during peak de novo expression of key effectors can be used to fine-tune stimulation-dependent biological outcomes. Our data also show that critical consideration is required when extrapolating mouse data to the human system in basic and translational research

    Localization of dexamethasone within dendritic core-multishell (CMS) nanoparticles and skin penetration properties studied by multi-frequency electron paramagnetic resonance (EPR) spectroscopy

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    The skin and especially the stratum corneum (SC) act as a barrier and protect epidermal cells and thus the whole body against xenobiotica of the external environment. Topical skin treatment requires an efficient drug delivery system (DDS). Polymer-based nanocarriers represent novel transport vehicles for dermal application of drugs. In this study dendritic core-multishell (CMS) nanoparticles were investigated as promising candidates. CMS nanoparticles were loaded with a drug (analogue) and were applied to penetration studies of skin. We determined by dual-frequency electron paramagnetic resonance (EPR) how dexamethasone (Dx) labelled with 3-carboxy-2,2,5,5-tetramethyl-1-pyrrolidinyloxy (PCA) is associated with the CMS. The micro-environment of the drug loaded to CMS nanoparticles was investigated by pulsed high-field EPR at cryogenic temperature, making use of the fact that magnetic parameters (g-, A-matrices, and spin-lattice relaxation time) represent specific probes for the micro-environment. Additionally, the rotational correlation time of spin-labelled Dx was probed by continuous wave EPR at ambient temperature, which provides independent information on the drug environment. Furthermore, the penetration depth of Dx into the stratum corneum of porcine skin after different topical applications was investigated. The location of Dx in the CMS nanoparticles is revealed and the function of CMS as penetration enhancers for topical application is shown

    Employment and continuing vocational training (CVT) in the German Microcensus of the year 2003

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    This paper is based on my thesis from the year 2008. It uses the German Microcensus (MC) to study the effects of continuing vocational training (CVT) on employment, the risk of unemployment, and wages. To control for education, profession and heterogeneity in the sectors and industrial branches in Germany individuals are separated into sub-groups. The results of my estimations indicate high returns to continuous vocational training in terms of lower risk to be unemployed, higher chances to be reemployed and higher chances to stay into an existing employment. The results also indicate that repeated short activities in CVT are more beneficial then long activities typically carried out by the German employment agency during the period of the Microcensus 2003

    P-Values as analytical tools in probabilistic forecast assessments.

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    Much has been written about ?quality? of probabilistic forecasts. Often, providers and users of such forecasts are unclear about what ?quality? entails, leading to confusion and misinformation. Here we try to provide some guidance and suggest a general approach to communicate aspects of probabilistic forecast quality related to discriminatory ability (DA) and skill (S). In our opinion, these two components of forecast quality should be considered independently. DA represents the additional knowledge about future states arising from some forecast system (FS) over and above the total variability of the prognostic variable while S quantifies changes in the agreement between observed and predicted values when using a specific FS instead of a FS based on ?climatology? only. The major concerns are: generally poor distinction between DA and S; inappropriate use of significance testing to quantify DA and use of DA and S measures that do not account for the series lengths and/or number of classes of the FS. To address all of these issues, we propose the use of p-values derived from non-parametric tests as direct measures of DA and S. We illustrate this approach by quantifying DA and S of the Southern Oscillation Index applied to forecasting rainfall across Australia

    Alternative splicing coupled mRNA decay shapes the temperature‐dependent transcriptome

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    Mammalian body temperature oscillates with the time of the dayand is altered in diverse pathological conditions. We recently iden-tified a body temperature-sensitive thermometer-like kinase,which alters SR protein phosphorylation and thereby globallycontrols alternative splicing (AS). AS can generate unproductivevariants which are recognized and degraded by diverse mRNAdecay pathways—including nonsense-mediated decay (NMD). Herewe show extensive coupling of body temperature-controlled AS tomRNA decay, leading to global control of temperature-dependentgene expression (GE). Temperature-controlled, decay-inducingsplicing events are evolutionarily conserved and pervasively foundwithin RNA-binding proteins, including most SR proteins. AS-coupledpoison exon inclusion is essential for rhythmic GE of SR proteins andhas a global role in establishing temperature-dependent rhythmicGE profiles, both in mammals under circadian body temperaturecycles and in plants in response to ambient temperature changes.Together, these data identify body temperature-driven AS-coupledmRNA decay as an evolutionary ancient, core clock-independentmechanism to generate rhythmic GE

    A process calculus with finitary comprehended terms

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    We introduce the notion of an ACP process algebra and the notion of a meadow enriched ACP process algebra. The former notion originates from the models of the axiom system ACP. The latter notion is a simple generalization of the former notion to processes in which data are involved, the mathematical structure of data being a meadow. Moreover, for all associative operators from the signature of meadow enriched ACP process algebras that are not of an auxiliary nature, we introduce variable-binding operators as generalizations. These variable-binding operators, which give rise to comprehended terms, have the property that they can always be eliminated. Thus, we obtain a process calculus whose terms can be interpreted in all meadow enriched ACP process algebras. Use of the variable-binding operators can have a major impact on the size of terms.Comment: 25 pages, combined with arXiv:0901.3012 [math.RA]; presentation improved, mistakes in Table 5 correcte
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