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Organic anion transporting polypeptide (Oatp) 1a/1b knockout and OATP1B1 and -1B3 humanized mouse models are promising tools for studying the roles of these transporters in drug disposition. Detailed characterization of these models will help to better understand their utility for predicting clinical outcomes. To advance this approach, we carried out a comprehensive analysis of these mouse lines by evaluating the compensatory changes in mRNA expression, quantifying the amounts of OATP1B1 and -1B3 protein by liquid chromatography–tandem mass spectrometry, and studying the active uptake in isolated hepatocytes and the pharmacokinetics of some prototypical substrates including statins. Major outcomes from these studies were 1) mostly moderate compensatory changes in only a few genes involved in drug metabolism and disposition, 2) a robust hepatic expression of OATP1B1 and -1B3 proteins in the respective humanized mouse models, and 3) functional activities of the human transporters in hepatocytes isolated from the humanized models with several substrates tested in vitro and with pravastatin in vivo. However, the expression of OATP1B1 and -1B3 in the humanized models did not significantly alter liver or plasma concentrations of rosuvastatin and pitavastatin compared with Oatp1a/1b knockout controls under the conditions used in our studies. Hence, although the humanized OATP1B1 and -1B3 mice showed in vitro and/or in vivo functional activity with some statins, further characterization of these models is required to define their potential use and limitations in the prediction of drug disposition and drug-drug interactions in humans.
Our knowledge on tree responses to drought is mainly based on short-term manipulation experiments which do not capture any possible long-term adjustments in this response. Therefore, historical water channels in inner-Alpine dry valleys were used as century-long irrigation experiments to investigate adjustments in tree growth to contrasting water supply. This involved quantifying the tree-ring growth of irrigated and non-irrigated (control) Scots pine (Pinus sylvestris L.) in Valais (Switzerland), as well as European larch (Larix decidua Mill.) and black pine (Pinus nigra Arnold) in Vinschgau (Italy). Furthermore, the adjustments in radial growth of Scots pine and European larch to an abrupt stop in irrigation were analyzed.
Irrigation promoted the radial growth of all tree species investigated compared to the control: (1) directly through increased soil water availability, and (2) indirectly through increased soil nutrients and humus contents in the irrigated plots. Irrigation led to a full elimination of growth responses to climate for European larch and black pine, but not for Scots pine, which might become more sensitive to drought with increasing tree size in Valais. For the control trees, the response of the latewood increment to water availability in July/August has decreased in recent decades for all species, but increased in May for Scots pine only. The sudden irrigation stop caused a drop in radial growth to a lower level for Scots pine or similar level for larch compared to the control for up to ten years. However, both tree species were then able to adjust to the new conditions and subsequently grew with similar (Scots pine) or even higher growth rates (larch) than the control.
To estimate the impact of climate change on future forest development, the duration of manipulation experiments should be on longer time scales in order to capture adjustment processes and feedback mechanisms of forest ecosystems.
Neue Dörfer braucht das Land! Dörfer in der Stadt und Dörfer auf dem Land (…). Die Planung und Gestaltung nachhaltiger Raumsysteme, die durch ein neues Verständnis des gemeinschaftlichen Besitzes (und dessen Nutzung) ressourcenfressende Individualisierungstendenzen unserer Gesellschaft überwinden, aber zugleich größtmöglichen Freiraum für eine individuelle Persönlichkeitsentfaltung zur Verfügung stellen." Dieses Zitat der Hamburger Initiative "Wir sind Dorf" beschreibt eine aktuelle Diskussion in unserer Gesellschaft, die sowohl in der Forschung und forschungsgeleiteten Initiativen, in Politik und Planung als auch in der Bürger-schaft stattfindet. Sie wird nicht nur auf wissenschaftlichen Veranstaltungen geführt, sondern auch in konkreten Projekten für integrative Lebenswelten, die Fragestellungen von Ernährung und Energieversorgung, von Arbeit und Ökonomie, aber auch eines neuen räumlichen und sozialen Miteinanders einbeziehen.
Anders als bei den weit verbreiteten Baugruppen geht es nicht ausschließlich um die Schaffung von Wohnraum. Die Nachbarschaftsidee verbindet das Bedürfnis nach gemeinschaftlichem Wohnen und Wirtschaften mit einer neuen Werteorientierung, die auf persönlicher Verantwortungsübernahme beruht.
The concept of an injective affine embedding of the quantum states into a set of classical states, i.e., into the set of the probability measures on some measurable space, as well as its relation to statistically complete observables is revisited, and its limitation in view of a classical reformulation of the statistical scheme of quantum mechanics is discussed. In particular, on the basis of a theorem concerning a non-denseness property of a set of coexistent effects, it is shown that an injective classical embedding of the quantum states cannot be supplemented by an at least approximate classical description of the quantum mechanical effects. As an alternative approach, the concept of quasi-probability representations of quantum mechanics is considered.