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Dermal Delivery of the High-Molecular-Weight Drug Tacrolimus by Means of Polyglycerol-Based Nanogels
(2019)
Rancan, Fiorenza ; Volkmann, Hildburg ; Giulbudagian, Michael ; Schumacher, Fabian ; Stanko, Jessica Isolde ; Kleuser, Burkhard ; Blume-Peytavi, Ulrike ; Calderon, Marcelo ; Vogt, Annika
Polyglycerol-based thermoresponsive nanogels (tNGs) have been shown to have excellent skin hydration properties and to be valuable delivery systems for sustained release of drugs into skin. In this study, we compared the skin penetration of tacrolimus formulated in tNGs with a commercial 0.1% tacrolimus ointment. The penetration of the drug was investigated in ex vivo abdominal and breast skin, while different methods for skin barrier disruption were investigated to improve skin permeability or simulate inflammatory conditions with compromised skin barrier. The amount of penetrated tacrolimus was measured in skin extracts by liquid chromatography tandem-mass spectrometry (LC-MS/MS), whereas the inflammatory markers IL-6 and IL-8 were detected by enzyme-linked immunosorbent assay (ELISA). Higher amounts of tacrolimus penetrated in breast as compared to abdominal skin or in barrier-disrupted as compared to intact skin, confirming that the stratum corneum is the main barrier for tacrolimus skin penetration. The anti-proliferative effect of the penetrated drug was measured in skin tissue/Jurkat cells co-cultures. Interestingly, tNGs exhibited similar anti-proliferative effects as the 0.1% tacrolimus ointment. We conclude that polyglycerol-based nanogels represent an interesting alternative to paraffin-based formulations for the treatment of inflammatory skin conditions.
This paper analyzes a specific section of Martial’s Apophoreta (Book 14), the ‘list’ of fourteen literary works that the poet-persona suggests to the reader as potentially suitable presents to give to friends on the occasion of the Saturnalia. It focuses strictly on the literary aspects of the poems and their underlying carnivalesque poetics. This includes an assessment of the logic of the poems’ arrangement and alleged inconsistencies. It is suggested that the section be read as a complex statement of Martial’s on various works and genres of Greek and Roman literature. The last couplet of the section (14.196), a certain Calvus’ work ‘On the use of cold water’ (De aquae frigidae usu), which is unidentifiable, receives particular attention, for previous scholarship has wasted a lot of ink on guessing what kind of work this may have been, thereby losing touch with the rich (meta-)poetics the couplet actually conveys.
Pump-probe photoelectron spectroscopy (PES) is a versatile tool to investigate the dynamics of transient states of excited matter. Vacuum space-charge effects can mask these dynamics and complicate the interpretation of electron spectra. Here we report on space-charge effects in Au 4f photoemission from a polycrystalline gold surface, excited with moderately intense 90 ps (FWHM) soft x-ray probe pulses, under the influence of the Coulomb forces exerted by a pump electron cloud, which was produced by intense 40 fs laser pulses. The experimentally observed kinetic energy shift and spectral broadening of the Au 4f lines, measured with highly-efficient time-of-flight spectroscopy, are in good agreement with simulations utilizing a mean-field model of the electrostatic pump electron potential. This confirms that the line broadening is predominantly caused by variations in the take-off time of the probe electrons without appreciable influence of local scattering events. Our findings might be of general interest for pump-probe PES with picosecond-pulse-length sources.
The dataset in the present article provides information on protozoic silicon (Si) pools represented by euglyphid testate amoebae (TA) in soils of initial and forested biogeosystems. Protozoic Si pools were calculated from densities of euglyphid TA shells and corresponding Si contents. The article also includes data on potential annual biosilicification rates of euglyphid TA at the examined sites. Furthermore, data on selected soil parameters (e.g., readily-available Si, soil pH) and site characteristics (e.g., soil groups, climate data) can be found. The data might be interesting for researchers focusing on biological processes in Si cycling in general and euglyphid TA and corresponding protozoic Si pools in particular.
Wojcik, Robin ; Donhauser, Johanna ; Frey, Beat W. ; Holm, Stine ; Holland, Alexandra ; Anesio, Alexandre M. ; Pearce, David A. ; Malard, Lucie ; Wagner, Dirk ; Benning, Liane G.
Proglacial environments are ideal for studying the development of soils through the changes of rocks exposed by glacier retreat to weathering and microbial processes. Carbon (C) and nitrogen (N) contents as well as soil pH and soil elemental compositions are thought to be dominant factors structuring the bacterial, archaeal and fungal communities in the early stages of soil ecosystem formation. However, the functional linkages between C and N contents, soil composition and microbial community structures remain poorly understood. Here, we describe a multivariate analysis of geochemical properties and associated microbial community structures between a moraine and a glaciofluvial outwash in the proglacial area of a High Arctic glacier (Longyearbreen, Svalbard). Our results reveal distinct differences in developmental stages and heterogeneity between the moraine and the glaciofluvial outwash. We observed significant relationships between C and N contents, delta C-13(org) and delta N-15 isotopic ratios, weathering and microbial abundance and community structures. We suggest that the observed differences in microbial and geochemical parameters between the moraine and the glaciofluvial outwash are primarily a result of geomorphological variations of the proglacial terrain.
John, Cathleen ; Grune, Jana ; Ott, Christiane ; Nowotny, Kerstin ; Deubel, Stefanie ; Kühne, Arne ; Schubert, Carola ; Kintscher, Ulrich ; Regitz-Zagrosek, Vera ; Grune, Tilman
Background: Obesity is a risk factor for diseases including type 2 diabetes mellitus (T2DM) and cardiovascular disorders. Diabetes itself contributes to cardiac damage. Thus, studying cardiovascular events and establishing therapeutic intervention in the period of type T2DM onset and manifestation are of highest importance. Mitochondrial dysfunction is one of the pathophysiological mechanisms leading to impaired cardiac function. Methods: An adequate animal model for studying pathophysiology of T2DM is the New Zealand Obese (NZO) mouse. These mice were maintained on a high-fat diet (HFD) without carbohydrates for 13 weeks followed by 4 week HFD with carbohydrates. NZO mice developed severe obesity and only male mice developed manifest T2DM. We determined cardiac phenotypes and mitochondrial function as well as cardiomyocyte signaling in this model. Results: The development of an obese phenotype and T2DM in male mice was accompanied by an impaired systolic function as judged by echocardiography and MyH6/7 expression. Moreover, the mitochondrial function only in male NZO hearts was significantly reduced and ERK1/2 and AMPK protein levels were altered. Conclusions: This is the first report demonstrating that the cardiac phenotype in male diabetic NZO mice is associated with impaired cardiac energy function and signaling events.
8-Allylcoumarins are conveniently accessible through a microwave-promoted tandem Claisen rearrangement/Wittig olefination/cyclization sequence. They serve as a versatile platform for the annellation of five- to seven-membered rings using ring-closing olefin metathesis (RCM). Furano-, pyrano-, oxepino- and azepinocoumarins were synthesized from the same set of precursors using Ru-catalyzed double bond isomerizations and RCM in a defined order. One class of products, pyrano[2,3-f]chromene-2,8-diones, were inaccessible through direct RCM of an acrylate, but became available from the analogous allyl ether via an assisted tandem catalytic RCM/allylic oxidation sequence.
Even simple mental arithmetic is fraught with cognitive biases. For example, adding repeated numbers (so-called tie problems, e.g., 2 + 2) not only has a speed and accuracy advantage over adding different numbers (e.g., 1 + 3) but may also lead to under-representation of the result relative to a standard value (Charras et al., 2012, 2014). Does the tie advantage merely reflect easier encoding or retrieval compared to non-ties, or also a distorted result representation? To answer this question, 47 healthy adults performed two tasks, both of which indicated under-representation of tie results: In a result-to-position pointing task (Experiment 1) we measured the spatial mapping of numbers and found a left-bias for tie compared to non-tie problems. In a result-to-line-length production task (Experiment 2) we measured the underlying magnitude representation directly and obtained shorter lines for tie-compared to non-tie problems. These observations suggest that the processing benefit of tie problems comes at the cost of representational reduction of result meaning. This conclusion is discussed in the context of a recent model of arithmetic heuristics and biases.
Al-Halbouni, Djamil ; Holohan, Eoghan P. ; Taheri, Abbas ; Watson, Robert A. ; Polom, Ulrich ; Schoepfer, Martin P. J. ; Emam, Sacha ; Dahm, Torsten
The 2-D distinct element method (DEM) code (PFC2D_V5) is used here to simulate the evolution of subsidence-related karst landforms, such as single and clustered sinkholes, and associated larger-scale depressions. Subsurface material in the DEM model is removed progressively to produce an array of cavities; this simulates a network of subsurface groundwater conduits growing by chemical/mechanical erosion. The growth of the cavity array is coupled mechanically to the gravitationally loaded surroundings, such that cavities can grow also in part by material failure at their margins, which in the limit can produce individual collapse sinkholes. Two end-member growth scenarios of the cavity array and their impact on surface subsidence were examined in the models: (1) cavity growth at the same depth level and growth rate; (2) cavity growth at progressively deepening levels with varying growth rates. These growth scenarios are characterised by differing stress patterns across the cavity array and its overburden, which are in turn an important factor for the formation of sinkholes and uvalalike depressions. For growth scenario (1), a stable compression arch is established around the entire cavity array, hindering sinkhole collapse into individual cavities and favouring block-wise, relatively even subsidence across the whole cavity array. In contrast, for growth scenario (2), the stress system is more heterogeneous, such that local stress concentrations exist around individual cavities, leading to stress interactions and local wall/overburden fractures. Consequently, sinkhole collapses occur in individual cavities, which results in uneven, differential subsidence within a larger-scale depression. Depending on material properties of the cavity-hosting material and the overburden, the larger-scale depression forms either by sinkhole coalescence or by widespread subsidence linked geometrically to the entire cavity array. The results from models with growth scenario (2) are in close agreement with surface morphological and subsurface geophysical observations from an evaporite karst area on the eastern shore of the Dead Sea.
OpenForecast
(2019)
Ayzel, Georgy ; Varentsova, Natalia ; Erina, Oxana ; Sokolov, Dmitriy ; Kurochkina, Liubov ; Moreydo, Vsevolod
The development and deployment of new operational runoff forecasting systems are a strong focus of the scientific community due to the crucial importance of reliable and timely runoff predictions for early warnings of floods and flashfloods for local businesses and communities. OpenForecast, the first operational runoff forecasting system in Russia, open for public use, is presented in this study. We developed OpenForecast based only on open-source software and data-GR4J hydrological model, ERA-Interim meteorological reanalysis, and ICON deterministic short-range meteorological forecasts. Daily forecasts were generated for two basins in the European part of Russia. Simulation results showed a limited efficiency in reproducing the spring flood of 2019. Although the simulations managed to capture the timing of flood peaks, they failed in estimating flood volume. However, further implementation of the parsimonious data assimilation technique significantly alleviates simulation errors. The revealed limitations of the proposed operational runoff forecasting system provided a foundation to outline its further development and improvement.
Heinrich, Ingo ; Balanzategui, Daniel ; Bens, Oliver ; Blasch, Gerald ; Blume, Theresa ; Boettcher, Falk ; Borg, Erik ; Brademann, Brian ; Brauer, Achim ; Conrad, Christopher ; Dietze, Elisabeth ; Dräger, Nadine ; Fiener, Peter ; Gerke, Horst H. ; Güntner, Andreas ; Heine, Iris ; Helle, Gerhard ; Herbrich, Marcus ; Harfenmeister, Katharina ; Heussner, Karl-Uwe ; Hohmann, Christian ; Itzerott, Sibylle ; Jurasinski, Gerald ; Kaiser, Knut ; Kappler, Christoph ; Koebsch, Franziska ; Liebner, Susanne ; Lischeid, Gunnar ; Merz, Bruno ; Missling, Klaus Dieter ; Morgner, Markus ; Pinkerneil, Sylvia ; Plessen, Birgit ; Raab, Thomas ; Ruhtz, Thomas ; Sachs, Torsten ; Sommer, Michael ; Spengler, Daniel ; Stender, Vivien ; Stüve, Peter ; Wilken, Florian
The Northeast German Lowland Observatory (TERENO-NE) was established to investigate the regional impact of climate and land use change. TERENO-NE focuses on the Northeast German lowlands, for which a high vulnerability has been determined due to increasing temperatures and decreasing amounts of precipitation projected for the coming decades. To facilitate in-depth evaluations of the effects of climate and land use changes and to separate the effects of natural and anthropogenic drivers in the region, six sites were chosen for comprehensive monitoring. In addition, at selected sites, geoarchives were used to substantially extend the instrumental records back in time. It is this combination of diverse disciplines working across different time scales that makes the observatory TERENO-NE a unique observation platform. We provide information about the general characteristics of the observatory and its six monitoring sites and present examples of interdisciplinary research activities at some of these sites. We also illustrate how monitoring improves process understanding, how remote sensing techniques are fine-tuned by the most comprehensive ground-truthing site DEMMIN, how soil erosion dynamics have evolved, how greenhouse gas monitoring of rewetted peatlands can reveal unexpected mechanisms, and how proxy data provides a long-term perspective of current ongoing changes.
Annemarie, Ambühl ; Weiss, Irene M. ; Schierl, Petra ; Schmitzer, Ulrich ; Kirichenko, Alexander ; Heinemann, Matthias ; Weiß, Adrian ; Esposito, Paolo ; Grewing, Farouk F. ; Merli, Elena ; Feichtinger, Barbara ; Seng, Helmut ; Wieber, Anja ; Schollmeyer, Patrick ; Kranzdorf, Anna ; Werner, Eva ; Wöhrle, Georg ; Brinker, Wolfram ; Di Rocco, Emilia ; Wesselmann, Katharina ; Löbcke, Konrad ; Benedetti, Ginevra
This special birthday issue for Christine Walde, co-founder and co-editor of thersites, features contributions from colleagues and friends. The articles, essays, and book reviews, centering around the honoranda’s research interests as well as focusing on core topics of thersites, form a thematically varied mosaic (tessellae): innovative constructions of literary genres and poetics (especially bucolic, elegy, epic, and epigram), images of the city of Rome and its counterparts, sleep and dreams, history of classical scholarship, gender studies, and classical reception studies.