TY - JOUR A1 - Malem-Shinitski, Noa A1 - Opper, Manfred A1 - Reich, Sebastian A1 - Schwetlick, Lisa A1 - Seelig, Stefan A. A1 - Engbert, Ralf T1 - A mathematical model of local and global attention in natural scene viewing JF - PLoS Computational Biology : a new community journal N2 - Author summary
Switching between local and global attention is a general strategy in human information processing. We investigate whether this strategy is a viable approach to model sequences of fixations generated by a human observer in a free viewing task with natural scenes. Variants of the basic model are used to predict the experimental data based on Bayesian inference. Results indicate a high predictive power for both aggregated data and individual differences across observers. The combination of a novel model with state-of-the-art Bayesian methods lends support to our two-state model using local and global internal attention states for controlling eye movements.
Understanding the decision process underlying gaze control is an important question in cognitive neuroscience with applications in diverse fields ranging from psychology to computer vision. The decision for choosing an upcoming saccade target can be framed as a selection process between two states: Should the observer further inspect the information near the current gaze position (local attention) or continue with exploration of other patches of the given scene (global attention)? Here we propose and investigate a mathematical model motivated by switching between these two attentional states during scene viewing. The model is derived from a minimal set of assumptions that generates realistic eye movement behavior. We implemented a Bayesian approach for model parameter inference based on the model's likelihood function. In order to simplify the inference, we applied data augmentation methods that allowed the use of conjugate priors and the construction of an efficient Gibbs sampler. This approach turned out to be numerically efficient and permitted fitting interindividual differences in saccade statistics. Thus, the main contribution of our modeling approach is two-fold; first, we propose a new model for saccade generation in scene viewing. Second, we demonstrate the use of novel methods from Bayesian inference in the field of scan path modeling. Y1 - 2020 U6 - https://doi.org/10.1371/journal.pcbi.1007880 SN - 1553-734X SN - 1553-7358 VL - 16 IS - 12 PB - PLoS CY - San Fransisco ER - TY - JOUR A1 - Hartung, Niklas A1 - Borghardt, Jens Markus T1 - A mechanistic framework for a priori pharmacokinetic predictions of orally inhaled drugs JF - PLoS Computational Biology : a new community journal N2 - Author summary
The use of orally inhaled drugs for treating lung diseases is appealing since they have the potential for lung selectivity, i.e. high exposure at the site of action -the lung- without excessive side effects. However, the degree of lung selectivity depends on a large number of factors, including physiochemical properties of drug molecules, patient disease state, and inhalation devices. To predict the impact of these factors on drug exposure and thereby to understand the characteristics of an optimal drug for inhalation, we develop a predictive mathematical framework (a "pharmacokinetic model"). In contrast to previous approaches, our model allows combining knowledge from different sources appropriately and its predictions were able to adequately predict different sets of clinical data. Finally, we compare the impact of different factors and find that the most important factors are the size of the inhaled particles, the affinity of the drug to the lung tissue, as well as the rate of drug dissolution in the lung. In contrast to the common belief, the solubility of a drug in the lining fluids is not found to be relevant. These findings are important to understand how inhaled drugs should be designed to achieve best treatment results in patients.
The fate of orally inhaled drugs is determined by pulmonary pharmacokinetic processes such as particle deposition, pulmonary drug dissolution, and mucociliary clearance. Even though each single process has been systematically investigated, a quantitative understanding on the interaction of processes remains limited and therefore identifying optimal drug and formulation characteristics for orally inhaled drugs is still challenging. To investigate this complex interplay, the pulmonary processes can be integrated into mathematical models. However, existing modeling attempts considerably simplify these processes or are not systematically evaluated against (clinical) data. In this work, we developed a mathematical framework based on physiologically-structured population equations to integrate all relevant pulmonary processes mechanistically. A tailored numerical resolution strategy was chosen and the mechanistic model was evaluated systematically against data from different clinical studies. Without adapting the mechanistic model or estimating kinetic parameters based on individual study data, the developed model was able to predict simultaneously (i) lung retention profiles of inhaled insoluble particles, (ii) particle size-dependent pharmacokinetics of inhaled monodisperse particles, (iii) pharmacokinetic differences between inhaled fluticasone propionate and budesonide, as well as (iv) pharmacokinetic differences between healthy volunteers and asthmatic patients. Finally, to identify the most impactful optimization criteria for orally inhaled drugs, the developed mechanistic model was applied to investigate the impact of input parameters on both the pulmonary and systemic exposure. Interestingly, the solubility of the inhaled drug did not have any relevant impact on the local and systemic pharmacokinetics. Instead, the pulmonary dissolution rate, the particle size, the tissue affinity, and the systemic clearance were the most impactful potential optimization parameters. In the future, the developed prediction framework should be considered a powerful tool for identifying optimal drug and formulation characteristics. Y1 - 2020 U6 - https://doi.org/10.1371/journal.pcbi.1008466 SN - 1553-734X SN - 1553-7358 VL - 16 IS - 12 PB - PLoS CY - San Fransisco ER - TY - JOUR A1 - Schiro, Gabriele A1 - Colangeli, Pierluigi A1 - Müller, Marina E. H. T1 - A Metabarcoding Analysis of the Mycobiome of Wheat Ears Across a Topographically Heterogeneous Field JF - Frontiers in microbiology KW - Fusarium KW - microclimate KW - canopy KW - fungal community KW - Alternaria KW - spatially induced variance Y1 - 2019 U6 - https://doi.org/10.3389/fmicb.2019.02095 SN - 1664-302X VL - 10 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Staubitz, Thomas A1 - Serth, Sebastian A1 - Thomas, Max A1 - Ebner, Martin A1 - Koschutnig-Ebner, Markus A1 - Rampelt, Florian A1 - von Stetten, Alexander A1 - Wittke, Andreas ED - Meinel, Christoph ED - Schweiger, Stefanie ED - Staubitz, Thomas ED - Conrad, Robert ED - Alario Hoyos, Carlos ED - Ebner, Martin ED - Sancassani, Susanna ED - Żur, Agnieszka ED - Friedl, Christian ED - Halawa, Sherif ED - Gamage, Dilrukshi ED - Scott, Jeffrey ED - Kristine Jonson Carlon, May ED - Deville, Yves ED - Gaebel, Michael ED - Delgado Kloos, Carlos ED - von Schmieden, Karen T1 - A metastandard for the international exchange of MOOCs BT - the MOOChub as first prototype JF - EMOOCs 2023 : Post-Covid Prospects for Massive Open Online Courses - Boost or Backlash? N2 - The MOOChub is a joined web-based catalog of all relevant German and Austrian MOOC platforms that lists well over 750 Massive Open Online Courses (MOOCs). Automatically building such a catalog requires that all partners describe and publicly offer the metadata of their courses in the same way. The paper at hand presents the genesis of the idea to establish a common metadata standard and the story of its subsequent development. The result of this effort is, first, an open-licensed de-facto-standard, which is based on existing commonly used standards and second, a first prototypical platform that is using this standard: the MOOChub, which lists all courses of the involved partners. This catalog is searchable and provides a more comprehensive overview of basically all MOOCs that are offered by German and Austrian MOOC platforms. Finally, the upcoming developments to further optimize the catalog and the metadata standard are reported. KW - Digitale Bildung KW - Kursdesign KW - MOOC KW - Micro Degree KW - Online-Lehre KW - Onlinekurs KW - Onlinekurs-Produktion KW - digital education KW - e-learning KW - micro degree KW - micro-credential KW - online course creation KW - online course design KW - online teaching Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-624154 SP - 147 EP - 161 PB - Universitätsverlag Potsdam CY - Potsdam ER - TY - JOUR A1 - Ramezani Ziarani, Maryam A1 - Bookhagen, Bodo A1 - Schmidt, Torsten A1 - Wickert, Jens A1 - de la Torre, Alejandro A1 - Deng, Zhiguo A1 - Calori, Andrea T1 - A model for the relationship between rainfall, GNSS-derived integrated water vapour, and CAPE in the eastern central Andes JF - Remote Sensing N2 - Atmospheric water vapour content is a key variable that controls the development of deep convective storms and rainfall extremes over the central Andes. Direct measurements of water vapour are challenging; however, recent developments in microwave processing allow the use of phase delays from L-band radar to measure the water vapour content throughout the atmosphere: Global Navigation Satellite System (GNSS)-based integrated water vapour (IWV) monitoring shows promising results to measure vertically integrated water vapour at high temporal resolutions. Previous works also identified convective available potential energy (CAPE) as a key climatic variable for the formation of deep convective storms and rainfall in the central Andes. Our analysis relies on GNSS data from the Argentine Continuous Satellite Monitoring Network, Red Argentina de Monitoreo Satelital Continuo (RAMSAC) network from 1999 to 2013. CAPE is derived from version 2.0 of the ECMWF’s (European Centre for Medium-Range Weather Forecasts) Re-Analysis (ERA-interim) and rainfall from the TRMM (Tropical Rainfall Measuring Mission) product. In this study, we first analyse the rainfall characteristics of two GNSS-IWV stations by comparing their complementary cumulative distribution function (CCDF). Second, we separately derive the relation between rainfall vs. CAPE and GNSS-IWV. Based on our distribution fitting analysis, we observe an exponential relation of rainfall to GNSS-IWV. In contrast, we report a power-law relationship between the daily mean value of rainfall and CAPE at the GNSS-IWV station locations in the eastern central Andes that is close to the theoretical relationship based on parcel theory. Third, we generate a joint regression model through a multivariable regression analysis using CAPE and GNSS-IWV to explain the contribution of both variables in the presence of each other to extreme rainfall during the austral summer season. We found that rainfall can be characterised with a higher statistical significance for higher rainfall quantiles, e.g., the 0.9 quantile based on goodness-of-fit criterion for quantile regression. We observed different contributions of CAPE and GNSS-IWV to rainfall for each station for the 0.9 quantile. Fourth, we identify the temporal relation between extreme rainfall (the 90th, 95th, and 99th percentiles) and both GNSS-IWV and CAPE at 6 h time steps. We observed an increase before the rainfall event and at the time of peak rainfall—both for GNSS-integrated water vapour and CAPE. We show higher values of CAPE and GNSS-IWV for higher rainfall percentiles (99th and 95th percentiles) compared to the 90th percentile at a 6-h temporal scale. Based on our correlation analyses and the dynamics of the time series, we show that both GNSS-IWV and CAPE had comparable magnitudes, and we argue to consider both climatic variables when investigating their effect on rainfall extremes. KW - Global Navigation Satellite System (GNSS) KW - GNSS-integrated water vapour KW - convective available potential energy (CAPE) KW - extreme rainfall KW - TRMM Y1 - 2021 U6 - https://doi.org/10.3390/rs13183788 SN - 2072-4292 VL - 13 IS - 18 PB - MDPI CY - Basel ER - TY - JOUR A1 - Hassanin, Alshaimaa A1 - Kliem, Bernhard A1 - Seehafer, Norbert A1 - Török, Tibor T1 - A model of homologous confined and ejective eruptions involving kink instability and flux cancellation JF - The astrophysical journal : an international review of spectroscopy and astronomical physics N2 - In this study, we model a sequence of a confined and a full eruption, employing the relaxed end state of the confined eruption of a kink-unstable flux rope as the initial condition for the ejective one. The full eruption, a model of a coronal mass ejection, develops as a result of converging motions imposed at the photospheric boundary, which drive flux cancellation. In this process, parts of the positive and negative external flux converge toward the polarity inversion line, reconnect, and cancel each other. Flux of the same amount as the canceled flux transfers to a flux rope, increasing the free magnetic energy of the coronal field. With sustained flux cancellation and the associated progressive weakening of the magnetic tension of the overlying flux, we find that a flux reduction of approximate to 11% initiates the torus instability of the flux rope, which leads to a full eruption. These results demonstrate that a homologous full eruption, following a confined one, can be driven by flux cancellation. Y1 - 2022 U6 - https://doi.org/10.3847/2041-8213/ac64a9 SN - 2041-8205 SN - 2041-8213 VL - 929 IS - 2 PB - IOP Publ. Ltd. CY - Bristol ER - TY - JOUR A1 - Pornsawad, Pornsarp A1 - Sapsakul, Nantawan A1 - Böckmann, Christine T1 - A modified asymptotical regularization of nonlinear ill-posed problems JF - Mathematics N2 - 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. KW - nonlinear operator KW - regularization KW - discrepancy principle KW - asymptotic method KW - optimal rate Y1 - 2019 U6 - https://doi.org/10.3390/math7050419 SN - 2227-7390 VL - 7 PB - MDPI CY - Basel, Schweiz ET - 5 ER - TY - JOUR A1 - Grebenkov, Denis S. A1 - Metzler, Ralf A1 - Oshanin, Gleb T1 - A molecular relay race: sequential first-passage events to the terminal reaction centre in a cascade of diffusion controlled processes JF - New Journal of Physics (NJP) N2 - We consider a sequential cascade of molecular first-reaction events towards a terminal reaction centre in which each reaction step is controlled by diffusive motion of the particles. The model studied here represents a typical reaction setting encountered in diverse molecular biology systems, in which, e.g. a signal transduction proceeds via a series of consecutive 'messengers': the first messenger has to find its respective immobile target site triggering a launch of the second messenger, the second messenger seeks its own target site and provokes a launch of the third messenger and so on, resembling a relay race in human competitions. For such a molecular relay race taking place in infinite one-, two- and three-dimensional systems, we find exact expressions for the probability density function of the time instant of the terminal reaction event, conditioned on preceding successful reaction events on an ordered array of target sites. The obtained expressions pertain to the most general conditions: number of intermediate stages and the corresponding diffusion coefficients, the sizes of the target sites, the distances between them, as well as their reactivities are arbitrary. KW - diffusion KW - reaction cascade KW - first passage time Y1 - 2021 U6 - https://doi.org/10.1088/1367-2630/ac1e42 SN - 1367-2630 VL - 23 PB - IOP - Institute of Physics Publishing CY - Bristol ER - TY - JOUR A1 - Perach, Shai A1 - Alexandron, Giora T1 - A MOOC-Based Computer Science Program for Middle School BT - Results, Challenges, and the Covid-19 Effect JF - EMOOCs 2021 N2 - In an attempt to pave the way for more extensive Computer Science Education (CSE) coverage in K-12, this research developed and made a preliminary evaluation of a blended-learning Introduction to CS program based on an academic MOOC. Using an academic MOOC that is pedagogically effective and engaging, such a program may provide teachers with disciplinary scaffolds and allow them to focus their attention on enhancing students’ learning experience and nurturing critical 21st-century skills such as self-regulated learning. As we demonstrate, this enabled us to introduce an academic level course to middle-school students. In this research, we developed the principals and initial version of such a program, targeting ninth-graders in science-track classes who learn CS as part of their standard curriculum. We found that the middle-schoolers who participated in the program achieved academic results on par with undergraduate students taking this MOOC for academic credit. Participating students also developed a more accurate perception of the essence of CS as a scientific discipline. The unplanned school closure due to the COVID19 pandemic outbreak challenged the research but underlined the advantages of such a MOOCbased blended learning program above classic pedagogy in times of global or local crises that lead to school closure. While most of the science track classes seem to stop learning CS almost entirely, and the end-of-year MoE exam was discarded, the program’s classes smoothly moved to remote learning mode, and students continued to study at a pace similar to that experienced before the school shut down. Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-517133 SN - 978-3-86956-512-5 VL - 2021 SP - 111 EP - 127 PB - Universitätsverlag Potsdam CY - Potsdam ER - TY - JOUR A1 - Winkelbeiner, Nicola Lisa A1 - Wandt, Viktoria Klara Veronika A1 - Ebert, Franziska A1 - Lossow, Kristina A1 - Bankoglu, Ezgi E. A1 - Martin, Maximilian A1 - Mangerich, Aswin A1 - Stopper, Helga A1 - Bornhorst, Julia A1 - Kipp, Anna Patricia A1 - Schwerdtle, Tanja T1 - A Multi-Endpoint Approach to Base Excision Repair Incision Activity Augmented by PARylation and DNA Damage Levels in Mice BT - Impact of Sex and Age JF - International Journal of Molecular Sciences N2 - Investigation of processes that contribute to the maintenance of genomic stability is one crucial factor in the attempt to understand mechanisms that facilitate ageing. The DNA damage response (DDR) and DNA repair mechanisms are crucial to safeguard the integrity of DNA and to prevent accumulation of persistent DNA damage. Among them, base excision repair (BER) plays a decisive role. BER is the major repair pathway for small oxidative base modifications and apurinic/apyrimidinic (AP) sites. We established a highly sensitive non-radioactive assay to measure BER incision activity in murine liver samples. Incision activity can be assessed towards the three DNA lesions 8-oxo-2’-deoxyguanosine (8-oxodG), 5-hydroxy-2’-deoxyuracil (5-OHdU), and an AP site analogue. We applied the established assay to murine livers of adult and old mice of both sexes. Furthermore, poly(ADP-ribosyl)ation (PARylation) was assessed, which is an important determinant in DDR and BER. Additionally, DNA damage levels were measured to examine the overall damage levels. No impact of ageing on the investigated endpoints in liver tissue were found. However, animal sex seems to be a significant impact factor, as evident by sex-dependent alterations in all endpoints investigated. Moreover, our results revealed interrelationships between the investigated endpoints indicative for the synergetic mode of action of the cellular DNA integrity maintaining machinery. KW - maintenance of genomic integrity KW - ageing KW - sex KW - DNA damage KW - base excision repair (incision activity) KW - DNA damage response KW - poly(ADP-ribosyl)ation KW - liver Y1 - 2020 U6 - https://doi.org/10.3390/ijms21186600 SN - 1422-0067 VL - 21 IS - 18 PB - Molecular Diversity Preservation International CY - Basel ER -