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Physiological Parameters Relevant to Dissolution Testing - Hydrodynamic Considerations (rev. and suppl. version)

2023, Diebold, Steffen M.

The first two sections of the monograph present an introduction into basic hydrodynamics relevant to in vitro dissolution testing including V. G. Levichs convective diffusion theory and the authors combination model. This part is followed by hydrodynamic considerations of in vivo dissolution including hydrodynamic problems inherent to in vivo bioavailability of solid oral dosage forms. Hydrodynamics in the upper GI tract contribute to in vivo dissolution. Our ability to forecast dissolution of poorly soluble drugs in vitro depends on our knowledge of and ability to control hydrodynamics as well as other factors influencing dissolution. Provided suitable conditions (apparatus, hydrodynamics, media) are chosen for the dissolution test, it seems possible to predict dissolution limitations to the oral absorption of drugs and to reflect variations in hydrodynamic conditions in the upper GI tract. The fluid volume available for dissolution in the gut lumen, the contact time of the dissolved compound with the absorptive sites and the particle size have been identified as the main hydrodynamic determinants for the absorption of poorly soluble drugs in vivo. The influence of these factors is usually more pronounced than that of the motility pattern or the gastrointestinal flow rates per se.

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The Global Gridded Crop Model Intercomparison phase 1 simulation dataset

2019, Müller, Christoph, Elliott, Joshua, Kelly, David, Arneth, Almut, Balkovic, Juraj, Ciais, Philippe, Deryng, Delphine, Folberth, Christian, Hoek, Steven, Izaurralde, Roberto C., Jones, Curtis D., Khabarov, Nikolay, Lawrence, Peter, Liu, Wenfeng, Olin, Stefan, Pugh, Thomas A. M., Reddy, Ashwan, Rosenzweig, Cynthia, Ruane, Alex C., Sakurai, Gen, Schmid, Erwin, Skalsky, Rastislav, Wang, Xuhui, de Wit, Allard, Yang, Hong

The Global Gridded Crop Model Intercomparison (GGCMI) phase 1 dataset of the Agricultural Model Intercomparison and Improvement Project (AgMIP) provides an unprecedentedly large dataset of crop model simulations covering the global ice-free land surface. The dataset consists of annual data fields at a spatial resolution of 0.5 arc-degree longitude and latitude. Fourteen crop modeling groups provided output for up to 11 historical input datasets spanning 1901 to 2012, and for up to three different management harmonization levels. Each group submitted data for up to 15 different crops and for up to 14 output variables. All simulations were conducted for purely rainfed and near-perfectly irrigated conditions on all land areas irrespective of whether the crop or irrigation system is currently used there. With the publication of the GGCMI phase 1 dataset we aim to promote further analyses and understanding of crop model performance, potential relationships between productivity and environmental impacts, and insights on how to further improve global gridded crop model frameworks. We describe dataset characteristics and individual model setup narratives. © 2019, The Author(s).

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Nitrosylation vs. oxidation – How to modulate cold physical plasmas for biological applications

2019, Lackmann, Jan-Wilm, Bruno, Giuliana, Jablonowski, Helena, Kogelheide, Friederike, Offerhaus, Björn, Held, Julian, Schulz-von der Gathen, Volker, Stapelmann, Katharina, von Woedtke, Thomas, Wende, Kristian

Thiol moieties are major targets for cold plasma-derived nitrogen and oxygen species, making CAPs convenient tools to modulate redox-signaling pathways in cells and tissues. The underlying biochemical pathways are currently under investigation but especially the role of CAP derived RNS is barely understood. Their potential role in protein thiol nitrosylation would be relevant in inflammatory processes such as wound healing and improving their specific production by CAP would allow for enhanced treatment options beyond the current application. The impact of a modified kINPen 09 argon plasma jet with nitrogen shielding on cysteine as a thiol-carrying model substance was investigated by FTIR spectroscopy and high-resolution mass spectrometry. The deposition of short-lived radical species was measured by electron paramagnetic resonance spectroscopy, long-lived species were quantified by ion chromatography (NO2-, NO3-) and xylenol orange assay (H2O2). Product profiles were compared to samples treated with the so-called COST jet, being introduced by a European COST initiative as a reference device, using both reference conditions as well as conditions adjusted to kINPen gas mixtures. While thiol oxidation was dominant under all tested conditions, an Ar + N2/O2 gas compositions combined with a nitrogen curtain fostered nitric oxide deposition and the desired generation of S-nitrosocysteine. Interestingly, the COST-jet revealed significant differences in its chemical properties in comparison to the kINPen by showing a more stable production of RNS with different gas admixtures, indicating a different •NO production pathway. Taken together, results indicate various chemical properties of kINPen and COST-jet as well as highlight the potential of plasma tuning not only by gas admixtures alone but by adjusting the surrounding atmosphere as well.

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Climate change and international migration: Exploring the macroeconomic channel

2022, Rikani, Albano, Frieler, Katja, Schewe, Jacob

International migration patterns, at the global level, can to a large extent be explained through economic factors in origin and destination countries. On the other hand, it has been shown that global climate change is likely to affect economic development over the coming decades. Here, we demonstrate how these future climate impacts on national income levels could alter the global migration landscape. Using an empirically calibrated global migration model, we investigate two separate mechanisms. The first is through destination-country income, which has been shown consistently to have a positive effect on immigration. As countries' income levels relative to each other are projected to change in the future both due to different rates of economic growth and due to different levels of climate change impacts, the relative distribution of immigration across destination countries also changes as a result, all else being equal. Second, emigration rates have been found to have a complex, inverted U-shaped dependence on origin-country income. Given the available migration flow data, it is unclear whether this dependence-found in spatio-temporal panel data-also pertains to changes in a given migration flow over time. If it does, then climate change will additionally affect migration patterns through origin countries' emigration rates, as the relative and absolute positions of countries on the migration "hump" change. We illustrate these different possibilities, and the corresponding effects of 3°C global warming (above pre-industrial) on global migration patterns, using climate model projections and two different methods for estimating climate change effects on macroeconomic development.

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Intestinal flow rates, absorption of felodipine from the small intestine and attributes of chyme collected at midgut from Labradors

2023, Diebold, Steffen M.

The objectives of the present study were (1) to investigate gastrointestinal hydrodynamics of Labradors as a model for human midgut (2) to examine various attributes of intestinal fluids in vivo and (3) to study the influence of hydrodynamics on the dissolution and absorption of a poorly soluble drug from various suspensions. Gastrointestinal flow rates were determined volumetrically using an aspiration method. Isotonic saline and 20 % glucose solutions were used to alter gastrointestinal hydrodynamics. Felodipine, a BCS class II substance, was suspended in these fluids. Osmolality, pH, bile acid concentration and drug solubility in various chyme samples were determined. Blood plasma levels of felodipine were recorded while gastrointestinal dissolution was ongoing. Fluid recovery at midgut fistula was significantly higher (>100 %) for glucose 20 % than for isotonic saline solutions (70 %). After administration of 200 ml glucose 20 % the (overall) grand median of differential gastrointestinal flow rates (DFR) was 8.3 ml/min.. Individual spike flow ranged from 20 up to 60 ml/min. Corresponding flow rates after administration of 200 ml isotonic saline were 35.0 ml/min. for the grand median including individual spike flows beyond 100 ml/min.. Within and between-dog variability in flow rate data was similar. In general, glucose solutions released more evenly. Following oral administration of glucose solution 20 % osmolality of intestinal fluids decreased within 40 min. from about 1000 mOsm. towards more physiological values of about 350 mOsm.. Saturation solubility of felodipine (Cs) in jejunal chyme after administration of either solution (saline or glucose) was determined to be about 10 (µg/ml) on average (median), exposing high variability with time! The intestinal solubility varied greatly within the course of an experiment. However, a strong correlation was observed between the aspirated fluid volume and the dissolved amount of felodipine confirming the well known relationship of Noyes, Whitney, Nernst and Brunner in-vivo. Grand median of pH in jejunal chyme of labradors was determined to be 6.68. Median values range from 4.38-7.62. The pharmacokinetic data showed a slight trend to differences based on particle size and on fluid administered.

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Plasma-MDS, a metadata schema for plasma science with examples from plasma technology

2020, Franke, Steffen, Paulet, Lucian, Schäfer, Jan, O'Connell, Deborah, Becker, Markus M.

A metadata schema, named Plasma-MDS, is introduced to support research data management in plasma science. Plasma-MDS is suitable to facilitate the publication of research data following the FAIR principles in domain-specific repositories and with this the reuse of research data for data driven plasma science. In accordance with common features in plasma science and technology, the metadata schema bases on the concept to separately describe the source generating the plasma, the medium in which the plasma is operated in, the target the plasma is acting on, and the diagnostics used for investigation of the process under consideration. These four basic schema elements are supplemented by a schema element with various attributes for description of the resources, i.e. the digital data obtained by the applied diagnostic procedures. The metadata schema is first applied for the annotation of datasets published in INPTDAT—the interdisciplinary data platform for plasma technology. © 2020, The Author(s).

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Improving Accuracy and Temporal Resolution of Learning Curve Estimation for within- and across-Session Analysis

2016, Deliano, Matthias, Tabelow, Karsten, König, Reinhard, Polzehl, Jörg

Estimation of learning curves is ubiquitously based on proportions of correct responses within moving trial windows. Thereby, it is tacitly assumed that learning performance is constant within the moving windows, which, however, is often not the case. In the present study we demonstrate that violations of this assumption lead to systematic errors in the analysis of learning curves, and we explored the dependency of these errors on window size, different statistical models, and learning phase. To reduce these errors in the analysis of single-subject data as well as on the population level, we propose adequate statistical methods for the estimation of learning curves and the construction of confidence intervals, trial by trial. Applied to data from an avoidance learning experiment with rodents, these methods revealed performance changes occurring at multiple time scales within and across training sessions which were otherwise obscured in the conventional analysis. Our work shows that the proper assessment of the behavioral dynamics of learning at high temporal resolution can shed new light on specific learning processes, and, thus, allows to refine existing learning concepts. It further disambiguates the interpretation of neurophysiological signal changes recorded during training in relation to learning.

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Global data on earthworm abundance, biomass, diversity and corresponding environmental properties

2021, Phillips, Helen R. P., Bach, Elizabeth M., Bartz, Marie L. C., Bennett, Joanne M., Beugnon, Rémy, Briones, Maria J. I., Brown, George G., Ferlian, Olga, Gongalsky, Konstantin B., Guerra, Carlos A., König-Ries, Birgitta, López-Hernández, Danilo, Loss, Scott R., Marichal, Raphael, Matula, Radim, Minamiya, Yukio, Moos, Jan Hendrik, Moreno, Gerardo, Morón-Ríos, Alejandro, Motohiro, Hasegawa, Muys, Bart, Krebs, Julia J., Neirynck, Johan, Norgrove, Lindsey, Novo, Marta, Nuutinen, Visa, Nuzzo, Victoria, Mujeeb Rahman, P., Pansu, Johan, Paudel, Shishir, Pérès, Guénola, Pérez-Camacho, Lorenzo, Orgiazzi, Alberto, Ponge, Jean-François, Prietzel, Jörg, Rapoport, Irina B., Rashid, Muhammad Imtiaz, Rebollo, Salvador, Rodríguez, Miguel Á., Roth, Alexander M., Rousseau, Guillaume X., Rozen, Anna, Sayad, Ehsan, Ramirez, Kelly S., van Schaik, Loes, Scharenbroch, Bryant, Schirrmann, Michael, Schmidt, Olaf, Schröder, Boris, Seeber, Julia, Shashkov, Maxim P., Singh, Jaswinder, Smith, Sandy M., Steinwandter, Michael, Russell, David J., Szlavecz, Katalin, Talavera, José Antonio, Trigo, Dolores, Tsukamoto, Jiro, Uribe-López, Sheila, de Valença, Anne W., Virto, Iñigo, Wackett, Adrian A., Warren, Matthew W., Webster, Emily R., Schwarz, Benjamin, Wehr, Nathaniel H., Whalen, Joann K., Wironen, Michael B., Wolters, Volkmar, Wu, Pengfei, Zenkova, Irina V., Zhang, Weixin, Cameron, Erin K., Eisenhauer, Nico, Wall, Diana H., Brose, Ulrich, Decaëns, Thibaud, Lavelle, Patrick, Loreau, Michel, Mathieu, Jérôme, Mulder, Christian, van der Putten, Wim H., Rillig, Matthias C., Thakur, Madhav P., de Vries, Franciska T., Wardle, David A., Ammer, Christian, Ammer, Sabine, Arai, Miwa, Ayuke, Fredrick O., Baker, Geoff H., Baretta, Dilmar, Barkusky, Dietmar, Beauséjour, Robin, Bedano, Jose C., Birkhofer, Klaus, Blanchart, Eric, Blossey, Bernd, Bolger, Thomas, Bradley, Robert L., Brossard, Michel, Burtis, James C., Capowiez, Yvan, Cavagnaro, Timothy R., Choi, Amy, Clause, Julia, Cluzeau, Daniel, Coors, Anja, Crotty, Felicity V., Crumsey, Jasmine M., Dávalos, Andrea, Cosín, Darío J. Díaz, Dobson, Annise M., Domínguez, Anahí, Duhour, Andrés Esteban, van Eekeren, Nick, Emmerling, Christoph, Falco, Liliana B., Fernández, Rosa, Fonte, Steven J., Fragoso, Carlos, Franco, André L. C., Fusilero, Abegail, Geraskina, Anna P., Gholami, Shaieste, González, Grizelle, Gundale, Michael J., López, Mónica Gutiérrez, Hackenberger, Branimir K., Hackenberger, Davorka K., Hernández, Luis M., Hirth, Jeff R., Hishi, Takuo, Holdsworth, Andrew R., Holmstrup, Martin, Hopfensperger, Kristine N., Lwanga, Esperanza Huerta, Huhta, Veikko, Hurisso, Tunsisa T., Iannone, Basil V., Iordache, Madalina, Irmler, Ulrich, Ivask, Mari, Jesús, Juan B., Johnson-Maynard, Jodi L., Joschko, Monika, Kaneko, Nobuhiro, Kanianska, Radoslava, Keith, Aidan M., Kernecker, Maria L., Koné, Armand W., Kooch, Yahya, Kukkonen, Sanna T., Lalthanzara, H., Lammel, Daniel R., Lebedev, Iurii M., Le Cadre, Edith, Lincoln, Noa K.

Earthworms are an important soil taxon as ecosystem engineers, providing a variety of crucial ecosystem functions and services. Little is known about their diversity and distribution at large spatial scales, despite the availability of considerable amounts of local-scale data. Earthworm diversity data, obtained from the primary literature or provided directly by authors, were collated with information on site locations, including coordinates, habitat cover, and soil properties. Datasets were required, at a minimum, to include abundance or biomass of earthworms at a site. Where possible, site-level species lists were included, as well as the abundance and biomass of individual species and ecological groups. This global dataset contains 10,840 sites, with 184 species, from 60 countries and all continents except Antarctica. The data were obtained from 182 published articles, published between 1973 and 2017, and 17 unpublished datasets. Amalgamating data into a single global database will assist researchers in investigating and answering a wide variety of pressing questions, for example, jointly assessing aboveground and belowground biodiversity distributions and drivers of biodiversity change.

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Cell stimulation versus cell death induced by sequential treatments with pulsed electric fields and cold atmospheric pressure plasma

2018, Steuer, Anna, Wolff, Christina M., von Woedtke, Thomas, Weltmann, Klaus-Dieter, Kolb, Juergen F.

Pulsed electric fields (PEFs) and cold atmospheric pressure plasma (CAP) are currently both investigated for medical applications. The exposure of cells to PEFs can induce the formation of pores in cell membranes and consequently facilitate the uptake of molecules. In contrast, CAP mainly acts through reactive species that are generated in the liquid environment. The objective of this study was to determine, if PEFs combined with plasma-treated cell culture medium can mutually reinforce effects on viability of mammalian cells. Experiments were conducted with rat liver epithelial WB-F344 cells and their tumorigenic counterpart WB-ras for a direct comparison of non-tumorigenic and tumorigenic cells from the same origin. Viability after treatments strongly depended on cell type and applied field strength. Notably, tumorigenic WB-ras cells responded more sensitive to the respective treatments than non-tumorigenic WB-F344 cells. More cells were killed when plasma-treated medium was applied first in combination with treatments with 100-μs PEFs. For the reversed treatment order, i.e. application of PEFs first, the combination with 100-ns PEFs resulted in a stimulating effect for non-tumorigenic but not for tumorigenic cells. The results suggest that other mechanisms, besides simple pore formation, contributed to the mutually reinforcing effects of the two methods.

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Monoclonal Antibodies 13A4 and AC133 Do Not Recognize the Canine Ortholog of Mouse and Human Stem Cell Antigen Prominin-1 (CD133)

2016, Thamm, Kristina, Graupner, Sylvi, Werner, Carsten, Huttner, Wieland B., Corbeil, Denis, Nabi, Ivan R

The pentaspan membrane glycoprotein prominin-1 (CD133) is widely used in medicine as a cell surface marker of stem and cancer stem cells. It has opened new avenues in stem cell-based regenerative therapy and oncology. This molecule is largely used with human samples or the mouse model, and consequently most biological tools including antibodies are directed against human and murine prominin-1. Although the general structure of prominin-1 including its membrane topology is conserved throughout the animal kingdom, its primary sequence is poorly conserved. Thus, it is unclear if anti-human and -mouse prominin-1 antibodies cross-react with their orthologs in other species, especially dog. Answering this issue is imperative in light of the growing number of studies using canine prominin-1 as an antigenic marker. Here, we address this issue by cloning the canine prominin-1 and use its overexpression as a green fluorescent protein fusion protein in Madin-Darby canine kidney cells to determine its immunoreactivity with antibodies against human or mouse prominin-1. We used immunocytochemistry, flow cytometry and immunoblotting techniques and surprisingly found no cross-species immunoreactivity. These results raise some caution in data interpretation when anti-prominin-1 antibodies are used in interspecies studies.