QUELQUES ASPECTS FONDAMENTAUX DANS LE FONCTIONNEMENT DES CHAMBRES A MIGRATION

En vue d'optimiser le fonctionnement des chambres à migration, différents coefficients de transport (vitesse, coefficient de diffusion, énergie caractéristique) de l'électron ont été calculés pour différentes valeurs de champ électrique et pour différents gaz (argon — gaz carbonique —isobutane — méthane —méthylal). Le comportement de l'électron dans les mélanges gazeux argon-isobutane est étudié particulièrement ainsi que l'action d'une faible quantité de méthylal sur ce comportement. L'influence de variations de pression et de température sur la vitesse de migration est également analysée. Quelques remarques intéressantes sont formulées à propos de la précision spatiale de détection des chambres à migration et de la limite intrinsèque de cette précision

In vitro PKA phosphorylation-mediated human PDE4A4 activation

AbstractThe PDE4 catalytic machinery comprises, in part, two divalent cations in a binuclear motif. Here we report that PDE4A4 expressed in Sf9 cells exhibits a biphasic Mg2+ dose–response (EC50 of ∼0.15 and >10 mM) in catalyzing cAMP hydrolysis. In vitro phosphorylation of PDE4A4 by the PKA-catalytic subunit increases the enzyme’s sensitivity to Mg2+, leading to 4-fold increased cAMP hydrolysis without affecting its Km. The phosphorylation also increases the potencies of (R)- and (S)-rolipram without affecting CDP-840 and SB-207499. The results support that modulating the cofactor binding affinity of PDE4 represents a mechanism for regulating its activity

State-of-the-Art Instrumentation Package to Support Model Organism Research in Space

Hardware was developed for the Ames student Fruit-Fly Experiment (AFEx) to support fly growth and analysis during spaceflight. The hardware consists of a 1.5U vented aluminum box that houses an acrylic habitat, video camera, LED lighting, and environmental sensors. Power is provided via two USB connectors, one of which also supports data downlink. While the hardware was designed for use with fruit flies, it will house plants on an upcoming mission and could be adapted for use with other systems

A conceptual model of organochlorine fate from a combined analysis of spatial and mid- to long-term trends of surface and ground water contamination in tropical areas (FWI)

In this study, we investigated the management of long-term environmental pollution by organic pollutants such as organochlorine pesticides. We set out to identify conditions that are conducive to reducing pollution levels for these persistent molecules and then propose a conceptual model of organochlorine fate in water. Our approach looked at spatio-temporal changes in pollutant contents in surface water (SW) and groundwater (GW) on a large scale, in order to decipher the respective roles of soil, geology, hydrology and past treatment practices. The case of chlordecone (CLD) on the island of Martinique (1100&thinsp;km2) was selected given the sampling campaigns carried out since 2007 over more than 150 sites. CLD, its metabolite chlordecone-5b-hydro (5bCLD) and the metabolite-to-parent-compound ratio were compared. As regards the spatial variability of water contamination, our results showed that banana cropping areas explained the location of contaminated SW and GW, whereas the combination of soil and geology factors explained the main spatial variability in the 5bCLD∕CLD ratio. For temporal variability, these conditions defined a high diversity of situations in terms of the duration of pollution, highlighting two groups: water draining old geological formations and ferralsols or vertisols vs. recent geology and andosols. A conceptual leaching model provided some key information to help interpret downward trends in CLD and 5bCLD observed in water. Lastly, a conceptual model of organochlorine fate is proposed to explain the diversity of the 5bCLD∕CLD ratio in water. Our conclusions highlight the combined role of soil and groundwater residence time for differentiating between conditions that are more conducive, or not, to the disappearance of CLD from the environment. This paper presents a model that provides an overall perception of organochlorine pesticide fate in the environment.</p

Pope Leo IX: A reforming pope?

No abstract available

Field Production and Functional Evaluation of Chloroplast-Derived Interferon-α2b

Type I interferons (IFNs) inhibit viral replication and cell growth and enhance the immune response, and therefore have many clinical applications. IFN-α2b ranks third in world market use for a biopharmaceutical, behind only insulin and erythropoietin. The average annual cost of IFN-α2b for the treatment of hepatitis C infection is $26 000, and is therefore unavailable to the majority of patients in developing countries. Therefore, we expressed IFN-α2b in tobacco chloroplasts, and transgenic lines were grown in the field after obtaining United States Department of Agriculture Animal and Plant Health Inspection Service (USDA-APHIS) approval. Stable, site-specific integration of transgenes into chloroplast genomes and homoplasmy through several generations were confirmed. IFN-α2b levels reached up to 20% of total soluble protein, or 3 mg per gram of leaf (fresh weight). Transgenic IFN-α2b had similar in vitrobiological activity to commercially produced PEG-Intron™ when tested for its ability to protect cells against cytopathic viral replication in the vesicular stomatitis virus cytopathic effect (VSV CPE) assay and to inhibit early-stage human immunodeficiency virus (HIV) infection. The antitumour and immunomodulating properties of IFN-α2b were also seen in vivo . Chloroplast-derived IFN-α2b increased the expression of major histocompatibility complex class I (MHC I) on splenocytes and the total number of natural killer (NK) cells. Finally, IFN-α2b purified from chloroplast transgenic lines (cpIFN-α2b) protected mice from a highly metastatic tumour line. This demonstration of high levels of expression of IFN-α2b, transgene containment and biological activity akin to that of commercial preparations of IFN-α2b facilitated the first field production of a plant-derived human blood protein, a critical step towards human clinical trials and commercialization

Functional Crosstalk between Type I and II Interferon through the Regulated Expression of STAT1

Small "priming" quantities of type I interferon enhance cellular responses to type II interferon by maintaining basal levels of STAT1, explaining the observed crosstalk between these two cytokines

Interferon-β Pretreatment of Conventional and Plasmacytoid Human Dendritic Cells Enhances Their Activation by Influenza Virus

Influenza virus produces a protein, NS1, that inhibits infected cells from releasing type I interferon (IFN) and blocks maturation of conventional dendritic cells (DCs). As a result, influenza virus is a poor activator of both mouse and human DCs in vitro. However, in vivo a strong immune response to virus infection is generated in both species, suggesting that other factors may contribute to the maturation of DCs in vivo. It is likely that the environment in which a DC encounters a virus would contain multiple pro-inflammatory molecules, including type I IFN. Type I IFN is a critical component of the viral immune response that initiates an antiviral state in cells, primarily by triggering a broad transcriptional program that interferes with the ability of virus to establish infection in the cell. In this study, we have examined the activation profiles of both conventional and plasmacytoid dendritic cells (cDCs and pDCs) in response to an influenza virus infection in the context of a type I IFN-containing environment. We found that both cDCs and pDCs demonstrate a greater activation response to influenza virus when pre-exposed to IFN-β (IFN priming); although, the priming kinetics are different in these two cell types. This strongly suggests that type I IFN functions not only to reduce viral replication in these immune cells, but also to promote greater DC activation during influenza virus infections

Lung vasodilatory response to inhaled iloprost in experimental pulmonary hypertension: amplification by different type phosphodiesterase inhibitors

Inhaled prostanoids and phosphodiesterase (PDE) inhibitors have been suggested for treatment of severe pulmonary hypertension. In catheterized rabbits with acute pulmonary hypertension induced by continuous infusion of the stable thromboxane analogue U46619, we asked whether sildenafil (PDE1/5/6 inhibitor), motapizone (PDE3 inhibitor) or 8-Methoxymethyl-IBMX (PDE1 inhibitor) synergize with inhaled iloprost. Inhalation of iloprost caused a transient pulmonary artery pressure decline, levelling off within <20 min, without significant changes in blood gases or systemic hemodynamics. Infusion of 8-Methoxymethyl-IBMX, motapizone and sildenafil caused each a dose-dependent decrease in pulmonary artery pressure, with sildenafil possessing the highest efficacy and at the same time selectivity for the pulmonary circulation. When combining a per se ineffective dose of each PDE inhibitor (200 μg/kg × min 8-Methoxymethyl-IBMX, 1 μg/kg × min sildenafil, 5 μg/kg × min motapizone) with subsequent iloprost nebulization, marked amplification of the prostanoid induced pulmonary vasodilatory response was noted and the area under the curve of P(PA )reduction was nearly threefold increased with all approaches, as compared to sole iloprost administration. Further amplification was achieved with the combination of inhaled iloprost with sildenafil plus motapizone, but not with sildenafil plus 8MM-IBMX. Systemic hemodynamics and gas exchange were not altered for all combinations. We conclude that co-administration of minute systemic doses of selective PDE inhibitors with inhaled iloprost markedly enhances and prolongs the pulmonary vasodilatory response to inhaled iloprost, with maintenance of pulmonary selectivity and ventilation perfusion matching. The prominent effect of sildenafil may be operative via both PDE1 and PDE5, and is further enhanced by co-application of a PDE3 inhibitor

The Bishopric of Bamberg in the Medieval World

Der Band „Das Bistum Bamberg in der Welt des Mittelalters“ bietet den um bibliographische Hinweise erweiterten Text der Vorträge, die im Rahmen der Ringvorlesung des Zentrums für Mittelalterstudien (ZEMAS) der Universität Bamberg im Jahr des tausendjährigen Bestehens der (Erz-)Diözese Bamberg gehalten wurden. Ausführlich behandelt wird die Gründung des Bistums 1007 und seine Entwicklung im weiteren Verlauf des Mittelalters. Neben den historischen kommen auch baugeschichtliche, kunsthistorische und literaturgeschichtliche Aspekte zur Sprache. Alle Vorträge sind vergleichend angelegt und zeigen auf, in welche größeren Prozesse Gründung und Entwicklung des Bistums Bamberg sich einfügen. Der Blick reicht daher von Bamberg und Oberfranken über Merseburg, Magdeburg, Prag, Regensburg, Kärnten, Konstanz und Eger bis nach Burgund, Istrien, Apulien und in die Werkstätten arabischer Elfenbeinschnitzer in Andalusien.The volume "The Diocese of Bamberg in the Medieval World" collects extended versions of papers presented in the Centre for Medieval Studies (ZEMAS) at the university of Bamberg lecture series commemorating the millenary anniversary of the (arch) diocese of Bamberg. The lectures address, in detail, the founding of the diocese in 1007 and its subsequent development over the course of the Middle Ages. Employing an interdisciplinary approach, the papers emphasize political history, architectural history, art history, and literary history. All the lectures are presented comparatively and demonstrate how the foundation and the development of the diocese of Bamberg are integrated in larger processes and developments. This perspective extends the scope of these papers from Bamberg and Upper Franconia to Merseburg, Magdeburg, Prague, Regensburg, Carinthia (Austria), Constance, and Cheb (Czech Republic) to Burgundy (France), Apulia (Italy), Istria (Croatia), and the workshops of Arab ivory carvers in Andalusia