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The knowledge of transformation pathways and identification of transformation products (TPs) of veterinary drugs is important for animal health, food, and environmental matters. The active agent Monensin (MON) belongs to the ionophore antibiotics and is widely used as a veterinary drug against coccidiosis in broiler farming. However, no electrochemically (EC) generated TPs of MON have been described so far. In this study, the online coupling of EC and mass spectrometry (MS) was used for the generation of oxidative TPs. EC-conditions were optimized with respect to working electrode material, solvent, modifier, and potential polarity. Subsequent LC/HRMS (liquid+ chromatography/high resolution mass spectrometry) and MS/MS experiments were performed to identify the structures of derived TPs by a suspected target analysis. The obtained EC-results were compared to TPs observed in metabolism tests with microsomes and hydrolysis experiments of MON. Five previously undescribed TPs of MON were identified in our EC/MS based study and one TP, which was already known from literature and found by a microsomal assay, could be confirmed. Two and three further TPs were found as products in microsomal tests and following hydrolysis, respectively. We found decarboxylation, O-demethylation and acid-catalyzed ring-opening reactions to be the major mechanisms of MON transformation
Dermal Delivery of the High-Molecular-Weight Drug Tacrolimus by Means of Polyglycerol-Based Nanogels
(2019)
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.
OpenForecast
(2019)
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.
Forest structure is a crucial component in the assessment of whether a forest is likely to act as a carbon sink under changing climate. Detailed 3D structural information about the tundra–taiga ecotone of Siberia is mostly missing and still underrepresented in current research due to the remoteness and restricted accessibility. Field based, high-resolution remote sensing can provide important knowledge for the understanding of vegetation properties and dynamics. In this study, we test the applicability of consumer-grade Unmanned Aerial Vehicles (UAVs) for rapid calculation of stand metrics in treeline forests. We reconstructed high-resolution photogrammetric point clouds and derived canopy height models for 10 study sites from NE Chukotka and SW Yakutia. Subsequently, we detected individual tree tops using a variable-window size local maximum filter and applied a marker-controlled watershed segmentation for the delineation of tree crowns. With this, we successfully detected 67.1% of the validation individuals. Simple linear regressions of observed and detected metrics show a better correlation (R2) and lower relative root mean square percentage error (RMSE%) for tree heights (mean R2 = 0.77, mean RMSE% = 18.46%) than for crown diameters (mean R2 = 0.46, mean RMSE% = 24.9%). The comparison between detected and observed tree height distributions revealed that our tree detection method was unable to representatively identify trees <2 m. Our results show that plot sizes for vegetation surveys in the tundra–taiga ecotone should be adapted to the forest structure and have a radius of >15–20 m to capture homogeneous and representative forest stands. Additionally, we identify sources of omission and commission errors and give recommendations for their mitigation. In summary, the efficiency of the used method depends on the complexity of the forest’s stand structure.
In this paper Lie group method in combination with Magnus expansion is utilized to develop a universal method applicable to solving a Sturm–Liouville problem (SLP) of any order with arbitrary boundary conditions. It is shown that the method has ability to solve direct regular (and some singular) SLPs of even orders (tested for up to eight), with a mix of (including non-separable and finite singular endpoints) boundary conditions, accurately and efficiently. The present technique is successfully applied to overcome the difficulties in finding suitable sets of eigenvalues so that the inverse SLP problem can be effectively solved. The inverse SLP algorithm proposed by Barcilon (1974) is utilized in combination with the Magnus method so that a direct SLP of any (even) order and an inverse SLP of order two can be solved effectively.
In this paper Lie group method in combination with Magnus expansion is utilized to develop a universal method applicable to solving a Sturm–Liouville problem (SLP) of any order with arbitrary boundary conditions. It is shown that the method has ability to solve direct regular (and some singular) SLPs of even orders (tested for up to eight), with a mix of (including non-separable and finite singular endpoints) boundary conditions, accurately and efficiently. The present technique is successfully applied to overcome the difficulties in finding suitable sets of eigenvalues so that the inverse SLP problem can be effectively solved. The inverse SLP algorithm proposed by Barcilon (1974) is utilized in combination with the Magnus method so that a direct SLP of any (even) order and an inverse SLP of order two can be solved effectively.
In this paper, we investigate the continuous version of modified iterative Runge–Kutta-type methods for nonlinear inverse ill-posed problems proposed in a previous work. The convergence analysis is proved under the tangential cone condition, a modified discrepancy principle, i.e., the stopping time T is a solution of ∥𝐹(𝑥𝛿(𝑇))−𝑦𝛿∥=𝜏𝛿+ for some 𝛿+>𝛿, and an appropriate source condition. We yield the optimal rate of convergence.
In this paper, we investigate the continuous version of modified iterative Runge–Kutta-type methods for nonlinear inverse ill-posed problems proposed in a previous work. The convergence analysis is proved under the tangential cone condition, a modified discrepancy principle, i.e., the stopping time T is a solution of ∥𝐹(𝑥𝛿(𝑇))−𝑦𝛿∥=𝜏𝛿+ for some 𝛿+>𝛿, and an appropriate source condition. We yield the optimal rate of convergence.
In animals and humans, behavior can be influenced by irrelevant stimuli, a phenomenon called Pavlovian-to-instrumental transfer (PIT). In subjects with substance use disorder, PIT is even enhanced with functional activation in the nucleus accumbens (NAcc) and amygdala. While we observed enhanced behavioral and neural PIT effects in alcohol-dependent subjects, we here aimed to determine whether behavioral PIT is enhanced in young men with high-risk compared to low-risk drinking and subsequently related functional activation in an a-priori region of interest encompassing the NAcc and amygdala and related to polygenic risk for alcohol consumption. A representative sample of 18-year old men (n = 1937) was contacted: 445 were screened, 209 assessed: resulting in 191 valid behavioral, 139 imaging and 157 genetic datasets. None of the subjects fulfilled criteria for alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders-IV-TextRevision (DSM-IV-TR). We measured how instrumental responding for rewards was influenced by background Pavlovian conditioned stimuli predicting action-independent rewards and losses. Behavioral PIT was enhanced in high-compared to low-risk drinkers (b = 0.09, SE = 0.03, z = 2.7, p < 0.009). Across all subjects, we observed PIT-related neural blood oxygen level-dependent (BOLD) signal in the right amygdala (t = 3.25, p(SVC) = 0.04, x = 26, y = -6, z = -12), but not in NAcc. The strength of the behavioral PIT effect was positively correlated with polygenic risk for alcohol consumption (r(s) = 0.17, p = 0.032). We conclude that behavioral PIT and polygenic risk for alcohol consumption might be a biomarker for a subclinical phenotype of risky alcohol consumption, even if no drug-related stimulus is present. The association between behavioral PIT effects and the amygdala might point to habitual processes related to out PIT task. In non-dependent young social drinkers, the amygdala rather than the NAcc is activated during PIT; possible different involvement in association with disease trajectory should be investigated in future studies.
This study presents the first suite of apatite fission-track (AFT) ages from the SE part of the Western Sudetes. AFT cooling ages from the Orlica-snie(z) over dotnik Dome and the Upper Nysa Klodzka Graben range from Late Cretaceous (84 Ma) to Early Palaeocene-Middle Eocene (64-45 Ma). The first stage of basin evolution (similar to 100-90 Ma) was marked by the formation of a local extensional depocentre and disruption of the Mesozoic planation surface. Subsequent far-field convergence of European microplates resulted in Coniacian-Santonian (similar to 89-83 Ma) thrust faulting. AFT data from both metamorphic basement and Mesozoic sedimentary cover indicate homogenous Late Cretaceous burial of the entire Western Sudetes. Thermal history modeling suggests that the onset of cooling could be constrained between 89 and 63 Ma with a climax during the Palaeocene-Middle Eocene basin inversion phase.
Die vorliegende Arbeit geht der Fragestellung nach, inwiefern der Beutelsbacher Konsens in einem ausgewählten Schulbuch für den Politikunterricht in der Sekundarstufe I in Brandenburg berücksichtigt wird. Um sich dieser Frage anzunähern, werden zunächst die drei Grundsätze des Konsenses wiedergegeben: das Überwältigungsverbot, das Kontroversitätsgebot und die Schülerorientierung. Da der Konsens, auch wenn er von einem Großteil der Fachdidaktikerinnen und Fachdidaktiker geteilt wird, immer wieder Gegenstand von Diskussionen ist, werden in einem ersten Schritt Ansätze zur Aktualisierung bzw. Erweiterung dargestellt und anschließend aktuelle Streitpunkte aufgezeigt. In einem kurzen Zwischenfazit wird dann ein für die Schulbuchanalyse unabdingliches, eindeutiges Verständnis des Konsenses entwickelt.
Im folgenden Schritt wird die Rolle von Schulbüchern als Lehr- und Lernmedien diskutiert. Dabei steht insbesondere die Frage im Zentrum, weshalb sich gerade Schulbücher für eine Analyse im Rahmen der vorliegenden Arbeit eignen. Vor diesem Hintergrund wird das Konzept der Schulbuchanalyse vorgestellt. In diesem Rahmen werden der Untersuchungsschwerpunkt (Kontroversitätsgebot) und der Untersuchungsgegenstand (Kontroverse um Migration und Integration) eingegrenzt. In der Folge wird das Schulbuch Politik und Co. 1 mithilfe des erarbeiteten Untersuchungsinstruments (Kodierleitfaden) analysiert. Zudem werden die Ergebnisse pointiert und die gewählte Vorgehensweise reflektiert.
Narratives are shaping our understanding of the world. They convey values and norms and point to desirable future developments. In this way, they justify and legitimize political actions and social practices. Once a narrative has emerged and this world view is supported by broad societal groups, narratives can provide powerful momentum to trigger innovation and changes in the course of action. Narratives, however, are not necessarily based on evidence and precise categories, but can instead be vague and ambiguous in order to be acceptable and attractive to different actors. However, the more open and inclusive a narrative is, the less impact can be expected. We investigate whether there is a shared narrative in research for the sustainable economy and how this can be evaluated in terms of its potential societal impact. The paper carves out the visions for the future that have been underlying the research projects conducted within the German Federal Ministry of Education and Research (BMBF) funding programme "The Sustainable Economy". It then analyzes whether these visions are compatible with narratives dominating societal discourse on the sustainable economy, and concludes how the use of visions and narratives in research can contribute to fostering societal transformations.
Bank filtration (BF) is an established indirect water-treatment technology. The quality of water gained via BF depends on the subsurface capture zone, the mixing ratio (river water versus ambient groundwater), spatial and temporal distribution of subsurface travel times, and subsurface temperature patterns. Surface-water infiltration into the adjacent aquifer is determined by the local hydraulic gradient and riverbed permeability, which could be altered by natural clogging, scouring and artificial decolmation processes. The seasonal behaviour of a BF system in Germany, and its development during and about 6 months after decolmation (canal reconstruction), was observed with a long-term monitoring programme. To quantify the spatial and temporal variation in the BF system, a transient flow and heat transport model was implemented and two model scenarios, 'with' and 'without' canal reconstruction, were generated. Overall, the simulated water heads and temperatures matched those observed. Increased hydraulic connection between the canal and aquifer caused by the canal reconstruction led to an increase of similar to 23% in the already high share of BF water abstracted by the nearby waterworks. Subsurface travel-time distribution substantially shifted towards shorter travel times. Flow paths with travel times <200 days increased by similar to 10% and those with <300 days by 15%. Generally, the periodic temperature signal, and the summer and winter temperature extrema, increased and penetrated deeper into the aquifer. The joint hydrological and thermal effects caused by the canal reconstruction might increase the potential of biodegradable compounds to further penetrate into the aquifer, also by potentially affecting the redox zonation in the aquifer.
When does life end?
(2019)
If you look at the question of the end-of-life legislation, one – or rather THE basic question – is particularly interesting: What is the "end of life"? What is death? Ofcourse, one can approach this question theologically or philosophically, but alsolegally and especially medically. Since the 1960 s, medical progress has made itpossible to distinguish between different individual points of time within the na-tural dying process. However, this raises the question as to which of these pointsof time is relevant for criminal law. This question, which is usually onsideredvery emotionally, will be examined in more detail in the paper.
Pride is linked to conviviality, to the practice of life-with-an-other, and to an awareness of the limitations of the life forms and life norms which guide and regulate the life of culturally, socially, and historically defined communities. Assuming this link, pride in living-together and conviviality appear as concepts creating a framework for future perspectives. But these concepts need a space in which they can unfold critically and confidently with a view to the future. For millennia, the literatures of the world have created this space of simulation and experimentation in which knowledge of how-to-live-with-an-other has been put down on paper through the open-ended tradition of writing. It is the space of the life forms and life norms of conviviality: it offers us prospective knowledge for the future by translating the imaginable into the thinkable, and the readable into the livable.
Assessments of psychotherapeutic competencies play a crucial role in research and training. However, research on the reliability and validity of such assessments is sparse. This study aimed to provide an overview of the current evidence and to provide an average interrater reliability (IRR) of psychotherapeutic competence ratings. A systematic review was conducted, and 20 studies reported in 32 publications were collected. These 20 studies were included in a narrative synthesis, and 20 coefficients were entered into the meta-analysis. Most primary studies referred to cognitive-behavioral therapies and the treatment of depression, used the Cognitive Therapy Scale, based ratings on videos, and trained the raters. Our meta-analysis revealed a pooled ICC of 0.82, but at the same time severe heterogeneity. The evidence map highlighted a variety of variables related to competence assessments. Further aspects influencing the reliability of competence ratings and regarding the considerable heterogeneity are discussed in detail throughout the manuscript.