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- ItemPhysiological Parameters Relevant to Dissolution Testing - Hydrodynamic Considerations (rev. and suppl. version)(Tübingen : Universitätsbibliothek Tübingen, 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.
- ItemIntestinal flow rates, absorption of felodipine from the small intestine and attributes of chyme collected at midgut from Labradors(Tübingen : Universitätsbibliothek Tübingen, 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.
- ItemGlobal data on earthworm abundance, biomass, diversity and corresponding environmental properties(London : Nature Publ. Group, 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.
- ItemPlasma-MDS, a metadata schema for plasma science with examples from plasma technology(London : Nature Publ. Group, 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).
- ItemClimate change and international migration: Exploring the macroeconomic channel(San Francisco, California, US : PLOS, 2022) Rikani, Albano; Frieler, Katja; Schewe, JacobInternational 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.
- ItemScanning electron microscopy preparation of the cellular actin cortex: A quantitative comparison between critical point drying and hexamethyldisilazane drying(San Francisco, California, US : PLOS, 2021) Schu, Moritz; Terriac, Emmanuel; Koch, Marcus; Paschke, Stephan; Lautenschläger, Franziska; Flormann, Daniel A.D.The cellular cortex is an approximately 200-nm-thick actin network that lies just beneath the cell membrane. It is responsible for the mechanical properties of cells, and as such, it is involved in many cellular processes, including cell migration and cellular interactions with the environment. To develop a clear view of this dense structure, high-resolution imaging is essential. As one such technique, electron microscopy, involves complex sample preparation procedures. The final drying of these samples has significant influence on potential artifacts, like cell shrinkage and the formation of artifactual holes in the actin cortex. In this study, we compared the three most used final sample drying procedures: critical-point drying (CPD), CPD with lens tissue (CPD-LT), and hexamethyldisilazane drying. We show that both hexamethyldisilazane and CPD-LT lead to fewer artifactual mesh holes within the actin cortex than CPD. Moreover, CPD-LT leads to significant reduction in cell height compared to hexamethyldisilazane and CPD. We conclude that the final drying procedure should be chosen according to the reduction in cell height, and so CPD-LT, or according to the spatial separation of the single layers of the actin cortex, and so hexamethyldisilazane.
- ItemIn vitro assembly of plasmid DNA for direct cloning in Lactiplantibacillus plantarum WCSF1(San Francisco, California, US : PLOS, 2023) Blanch-Asensio, Marc; Dey, Sourik; Sankaran, ShrikrishnanLactobacilli are gram-positive bacteria that are growing in importance for the healthcare industry and genetically engineering them as living therapeutics is highly sought after. However, progress in this field is hindered since most strains are difficult to genetically manipulate, partly due to their complex and thick cell walls limiting our capability to transform them with exogenous DNA. To overcome this, large amounts of DNA (>1 μg) are normally required to successfully transform these bacteria. An intermediate host, like E. coli, is often used to amplify recombinant DNA to such amounts although this approach poses unwanted drawbacks such as an increase in plasmid size, different methylation patterns and the limitation of introducing only genes compatible with the intermediate host. In this work, we have developed a direct cloning method based on in-vitro assembly and PCR amplification to yield recombinant DNA in significant quantities for successful transformation in L. plantarum WCFS1. The advantage of this method is demonstrated in terms of shorter experimental duration and the possibility to introduce a gene incompatible with E. coli into L. plantarum WCFS1.
- ItemA Gini approach to spatial CO2 emissions(San Francisco, California, US : PLOS, 2020) Zhou, Bin; Thies, Stephan; Gudipudi, Ramana; Lüdeke, Matthias K.B.; Kropp, Jürgen P.; Rybski, DiegoCombining global gridded population and fossil fuel based CO2 emission data at 1 km scale, we investigate the spatial origin of CO2 emissions in relation to the population distribution within countries. We depict the correlations between these two datasets by a quasi-Lorenz curve which enables us to discern the individual contributions of densely and sparsely populated regions to the national CO2 emissions. We observe pronounced country-specific characteristics and quantify them using an indicator resembling the Gini-index. As demonstrated by a robustness test, the Gini-index for each country arise from a compound distribution between the population and emissions which differs among countries. Relating these indices with the degree of socio-economic development measured by per capita Gross Domestic Product (GDP) at purchase power parity, we find a strong negative correlation between the two quantities with a Pearson correlation coefficient of -0.71. More specifically, this implies that in developing countries locations with large population tend to emit relatively more CO2, and in developed countries the opposite tends to be the case. Based on the relation to urban scaling, we discuss the implications for CO2 emissions from cities. Our results show that general statements with regard to the (in)efficiency of large cities should be avoided as it is subject to the socio-economic development of respective countries. Concerning the political relevance, our results suggest a differentiated spatial prioritization in deploying climate change mitigation measures in cities for developed and developing countries.
- ItemFuture heat stress to reduce people’s purchasing power(San Francisco, Ca. : PLOS, 2021) Kuhla, Kilian; Willner, Sven Norman; Otto, Christian; Wenz, Leonie; Levermann, AndersWith increasing carbon emissions rising temperatures are likely to impact our economies and societies profoundly. In particular, it has been shown that heat stress can strongly reduce labor productivity. The resulting economic perturbations can propagate along the global supply network. Here we show, using numerical simulations, that output losses due to heat stress alone are expected to increase by about 24% within the next 20 years, if no additional adaptation measures are taken. The subsequent market response with rising prices and supply shortages strongly reduces the consumers’ purchasing power in almost all countries including the US and Europe with particularly strong effects in India, Brazil, and Indonesia. As a consequence, the producing sectors in many regions temporarily benefit from higher selling prices while decreasing their production in quantity, whereas other countries suffer losses within their entire national economy. Our results stress that, even though climate shocks may stimulate economic activity in some regions and some sectors, their unpredictability exerts increasing pressure on people’s livelihood.
- ItemGuiding cell adhesion and motility by modulating cross-linking and topographic properties of microgel arrays(San Francisco, California, US : PLOS, 2021) Riegert, Janine; Töpel, Alexander; Schieren, Jana; Coryn, Renee; Dibenedetto, Stella; Braunmiller, Dominik; Zajt, Kamil; Schalla, Carmen; Rütten, Stephan; Zenke, Martin; Pich, Andrij; Sechi, Antonio; Blank, Kerstin G.Biomaterial-driven modulation of cell adhesion and migration is a challenging aspect of tissue engineering. Here, we investigated the impact of surface-bound microgel arrays with variable geometry and adjustable cross-linking properties on cell adhesion and migration. We show that cell migration is inversely correlated with microgel array spacing, whereas directionality increases as array spacing increases. Focal adhesion dynamics is also modulated by microgel topography resulting in less dynamic focal adhesions on surface-bound microgels. Microgels also modulate the motility and adhesion of Sertoli cells used as a model for cell migration and adhesion. Both focal adhesion dynamics and speed are reduced on microgels. Interestingly, Gas2L1, a component of the cytoskeleton that mediates the interaction between microtubules and microfilaments, is dispensable for the regulation of cell adhesion and migration on microgels. Finally, increasing microgel cross-linking causes a clear reduction of focal adhesion turnover in Sertoli cells. These findings not only show that spacing and rigidity of surface-grafted microgels arrays can be effectively used to modulate cell adhesion and motility of diverse cellular systems, but they also form the basis for future developments in the fields of medicine and tissue engineering.