Adaptive mesh refinement for the Landau–Lifshitz–Gilbert equation

We propose a new adaptive algorithm for the approximation of the Landau–Lifshitz–Gilbert equation via a higher-order tangent plane scheme. We show that the adaptive approximation satisfies an energy inequality and demonstrate numerically, that the adaptive algorithm outperforms uniform approaches

The Interplay of Signaling Dynamics and Cell Cycle Regulation in Single Cells

Signaling pathways that control cellular responses such as proliferation, quiescence, migration and apoptosis are crucial for embryonic development, tissue homeostasis and regeneration. Dysregulation of these signaling processes can result in severe human diseases including cancer. Therefore, to maintain a balance between the above-mentioned cell fates and to prevent pathological events, an interplay between different signaling pathways is indispensable. For instance, mitogenic signaling induced by the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)-AKT networks is required for cells to enter the cell cycle and divide. However, to prevent uncontrolled proliferation, anti-mitogenic signals such as those transmitted by mothers against decapentaplegic homologue (SMAD) proteins are essential. To gain a deeper understanding of these pathway interactions, I employed quantitative time-resolved measurements of fluorescent reporters and computer-aided data analysis. In the first part of the present study, I examined how the MAPK and PI3K/AKT pathways synergize to regulate cell cycle entry and progression. Although these networks have been well characterized in earlier studies, their relative contribution, especially at later cell cycle stages, remains largely unexplored. In order to investigate the response of cells outside of an active cell cycle to acute mitogenic signals, untransformed human breast epithelial cells were first arrested in a quiescent state by growth factor deprivation. Afterwards, epidermal growth factor (EGF)-induced signal processing in individual cells was quantified over time, which revealed that both pathways were necessary for initial cell cycle entry, whereas only PI3K/AKT affected the duration of S-phase at later stages of mitogenic signaling. My results provide evidence that the high metabolic demands of replication are unmet in the absence of AKT signaling, which results in a strongly prolonged S-phase of the cell cycle. In the second part, I investigated how the cell cycle and mitogenic signals influence the SMAD signaling pathway. I uncovered that ligands of the transforming growth factor beta (TGFb) superfamily signaled very differently in quiescent versus proliferating cells. While TGFb mediated a stronger SMAD2 response in proliferating cells compared to quiescent cells, the opposite was observed upon growth differentiation factor 11 (GDF11) stimulation. I was able to show that MAPK activity was responsible for the switch in ligand sensitivity, most likely through regulation of target genes. Therefore, the question arose whether a single key player or a complete pathway-rewiring were accountable. As RNA sequencing revealed considerable changes in the expression of multiple SMAD associated genes and single perturbations of SMAD signaling regulators could not explain the observed phenomenon, I hypothesized that a more wide-ranging rewiring of the network is necessary to shift the sensitivity to different ligands of the TGFb superfamily. However, further studies using genome-scale knockout or activation screenings need to be carried out to validate this idea and recreate the pathway-rewiring in proliferating cells. Besides the switch in ligand sensitivity, I observed different SMAD-mediated cell fates in proliferating and quiescent cells. While apoptosis was only induced in quiescent cells, epithelial to mesenchymal transition (EMT) and cytostasis were found in dividing cells. Interestingly, cellular responses correlated well with the dynamics of SMAD signaling, which suggested that ligands mediate diverse cellular outcomes through different dynamical patterns of SMAD2 nuclear accumulation. This quantitative nature of the pathway was later validated by real-time quantitative PCR (RT-qPCR) and RNA sequencing

Micron‐Sized Pored Membranes Based on Polyvinylidene Difluoride Hexafluoropropylene Prepared by Phase Inversion Techniques

In this study, micron‐sized pored membranes, based on the co‐polymer polyvinylidene difluoride hexafluoropropylene (PVdF‐HFP) were prepared via phase inversion techniques. The aim of the approach was to find less harmful and less toxic solvents to fabricate such films. Therefore, the Hansen solubility approach was used to identify safer and less toxic organic solvents for the phase inversion process, relative to present solvent mixtures, based on acetone, dimethyl formamide, dimethyl acetamide or methanol. With this approach, it was possible to identify cyclopentanone, ethylene glycol and benzyl alcohol as suitable solvents for the membrane preparation process. Physicochemical and mechanical properties were analyzed and compared, which revealed a uniform membrane structure through the cross section. Differences were observed at the top surface, in dependence of both preparation approaches, which are described in detail

Beratung, Organisation, Profession - Die gescheiterte Professionalisierung in der Organisationsentwicklung, systemischen Beratung und Managementberatung

Kühl S, Bohn U. Beratung, Organisation, Profession - Die gescheiterte Professionalisierung in der Organisationsentwicklung, systemischen Beratung und Managementberatung. In: Schützeichel R, Brüsemeister T, eds. Die beratene Gesellschaft. Zur gesellschaftlichen Bedeutung von Beratung. Opladen: VS Verlag; 2004: 57-77

Emergence of fractal geometries in the evolution of a metabolic enzyme

Fractals are patterns that are self-similar across multiple length-scales. Macroscopic fractals are common in nature; however, so far, molecular assembly into fractals is restricted to synthetic systems. Here we report the discovery of a natural protein, citrate synthase from the cyanobacterium Synechococcus elongatus, which self-assembles into Sierpiński triangles. Using cryo-electron microscopy, we reveal how the fractal assembles from a hexameric building block. Although different stimuli modulate the formation of fractal complexes and these complexes can regulate the enzymatic activity of citrate synthase in vitro, the fractal may not serve a physiological function in vivo. We use ancestral sequence reconstruction to retrace how the citrate synthase fractal evolved from non-fractal precursors, and the results suggest it may have emerged as a harmless evolutionary accident. Our findings expand the space of possible protein complexes and demonstrate that intricate and regulatable assemblies can evolve in a single substitution

Dopamine D3 receptor dysfunction prevents anti-nociceptive effects of morphine in the spinal cord

Abstract Dopamine (DA) modulates spinal reflexes, including nociceptive reflexes, in part via the D3 receptor subtype. We have previously shown that mice lacking the functional D3 receptor (D3KO) exhibit decreased paw withdrawal latencies from painful thermal stimuli. Altering the DA system in the CNS, including D1 and D3 receptor systems, reduces the ability of opioids to provide analgesia. Here, we tested if the increased pain sensitivity in D3KO might result from a modified μ-opioid receptor (MOR) function at the spinal cord level. As D1 and D3 receptor subtypes have competing cellular effects and can form heterodimers, we tested if the changes in MOR function may be mediated in D3KO through the functionally intact D1 receptor system. We assessed thermal paw withdrawal latencies in D3KO and wild type (WT) mice before and after systemic treatment with morphine, determined MOR and phosphorylated MOR (p-MOR) protein expression levels in lumbar spinal cords, and tested the functional effects of DA and MOR receptor agonists in the isolated spinal cord. In vivo, a single morphine administration (2 mg/kg) increased withdrawal latencies in WT but not D3KO, and these differential effects were mimicked in vitro, where morphine modulated spinal reflex amplitudes (SRAs) in WT but not D3KO. Total MOR protein expression levels were similar between WT and D3KO, but the ratio of pMOR/total MOR was higher in D3KO. Blocking D3 receptors in the isolated WT cord precluded morphine's inhibitory effects observed under control conditions. Lastly, we observed an increase in D1 receptor protein expression in the lumbar spinal cord of D3KO. Our data suggest that the D3 receptor modulates the MOR system in the spinal cord, and that a dysfunction of the D3 receptor can induce a morphine-resistant state. We propose that the D3KO mouse may serve as a model to study the onset of morphine resistance at the spinal cord level, the primary processing site of the nociceptive pathway

The HD(CP)² Observational Prototype Experiment (HOPE) – an overview

The HD(CP)2 Observational Prototype Experiment (HOPE) was performed as a major 2-month field experiment in Jülich, Germany, in April and May 2013, followed by a smaller campaign in Melpitz, Germany, in September 2013. HOPE has been designed to provide an observational dataset for a critical evaluation of the new German community atmospheric icosahedral non-hydrostatic (ICON) model at the scale of the model simulations and further to provide information on land-surface–atmospheric boundary layer exchange, cloud and precipitation processes, as well as sub-grid variability and microphysical properties that are subject to parameterizations. HOPE focuses on the onset of clouds and precipitation in the convective atmospheric boundary layer. This paper summarizes the instrument set-ups, the intensive observation periods, and example results from both campaigns. HOPE-Jülich instrumentation included a radio sounding station, 4 Doppler lidars, 4 Raman lidars (3 of them provide temperature, 3 of them water vapour, and all of them particle backscatter data), 1 water vapour differential absorption lidar, 3 cloud radars, 5 microwave radiometers, 3 rain radars, 6 sky imagers, 99 pyranometers, and 5 sun photometers operated at different sites, some of them in synergy. The HOPE-Melpitz campaign combined ground-based remote sensing of aerosols and clouds with helicopter- and balloon-based in situ observations in the atmospheric column and at the surface. HOPE provided an unprecedented collection of atmospheric dynamical, thermodynamical, and micro- and macrophysical properties of aerosols, clouds, and precipitation with high spatial and temporal resolution within a cube of approximately 10  ×  10  ×  10 km3. HOPE data will significantly contribute to our understanding of boundary layer dynamics and the formation of clouds and precipitation. The datasets have been made available through a dedicated data portal. First applications of HOPE data for model evaluation have shown a general agreement between observed and modelled boundary layer height, turbulence characteristics, and cloud coverage, but they also point to significant differences that deserve further investigations from both the observational and the modelling perspective

The PROFOUND Database for evaluating vegetation models and simulating climate impacts on European forests

Process-based vegetation models are widely used to predict local and global ecosystem dynamics and climate change impacts. Due to their complexity, they require careful parameterization and evaluation to ensure that projections are accurate and reliable. The PROFOUND Database (PROFOUND DB) provides a wide range of empirical data on European forests to calibrate and evaluate vegetation models that simulate climate impacts at the forest stand scale. A particular advantage of this database is its wide coverage of multiple data sources at different hierarchical and temporal scales, together with environmental driving data as well as the latest climate scenarios. Specifically, the PROFOUND DB provides general site descriptions, soil, climate, CO2, nitrogen deposition, tree and forest stand level, and remote sensing data for nine contrasting forest stands distributed across Europe. Moreover, for a subset of five sites, time series of carbon fluxes, atmospheric heat conduction and soil water are also available. The climate and nitrogen deposition data contain several datasets for the historic period and a wide range of future climate change scenarios following the Representative Concentration Pathways (RCP2.6, RCP4.5, RCP6.0, RCP8.5). We also provide pre-industrial climate simulations that allow for model runs aimed at disentangling the contribution of climate change to observed forest productivity changes. The PROFOUND DB is available freely as a "SQLite" relational database or "ASCII" flat file version (at https://doi.org/10.5880/PIK.2020.006/; Reyer et al., 2020). The data policies of the individual contributing datasets are provided in the metadata of each data file. The PROFOUND DB can also be accessed via the ProfoundData R package (https://CRAN.R- project.org/package=ProfoundData; Silveyra Gonzalez et al., 2020), which provides basic functions to explore, plot and extract the data for model set-up, calibration and evaluation.Peer reviewe