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Now showing 1 - 5 of 5
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    PDA Indolylmaleimides Induce Anti-Tumor Effects in Prostate Carcinoma Cell Lines Through Mitotic Death
    (Lausanne : Frontiers Research Foundation, 2021) Schille, Jan Torben; Nolte, Ingo; Beck, Julia; Jilani, Daria; Roolf, Catrin; Pews-Davtyan, Anahit; Rolfs, Arndt; Henze, Larissa; Beller, Matthias; Brenig, Bertram; Junghanss, Christian; Schütz, Ekkehard; Murua Escobar, Hugo
    Castrate resistant prostate cancer in men shares several characteristics with canine prostate cancer (PCa). Due to current insufficient therapies, evaluating novel therapeutic agents for late-stage PCa is of considerable interest for both species. PDA indolylmaleimides showed anticancer effects in several neoplastic cell lines. Herein, a comparative characterization of PDA-66 and PDA-377 mediated effects was performed in human and canine PCa cell lines, which is also the first detailed characterization of these agents on cells derived from solid tumors in general. While PDA-377 showed only weak growth inhibition on human PCa cell lines, PDA-66 inhibited proliferation and induced apoptosis in human and canine cell lines with concentrations in the low micromolar range. Morphological characterization and whole transcriptome sequencing revealed that PDA-66 induces mitotic death through its microtubule-depolymerizing ability. PDA-66 appears to be a worthwhile anti-mitotic agent for further evaluation. The similarities in cellular and molecular response observed in the cell lines of both origins form a solid basis for the use of canine PCa in vivo models to gain valuable interchangeable data to the advantage of both species.
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    Basins of attraction of chimera states on networks
    (Lausanne : Frontiers Research Foundation, 2022) Li, Qiang; Larosz, Kelly C.; Han, Dingding; Ji, Peng; Kurths, Jürgen
    Networks of identical coupled oscillators display a remarkable spatiotemporal pattern, the chimera state, where coherent oscillations coexist with incoherent ones. In this paper we show quantitatively in terms of basin stability that stable and breathing chimera states in the original two coupled networks typically have very small basins of attraction. In fact, the original system is dominated by periodic and quasi-periodic chimera states, in strong contrast to the model after reduction, which can not be uncovered by the Ott-Antonsen ansatz. Moreover, we demonstrate that the curve of the basin stability behaves bimodally after the system being subjected to even large perturbations. Finally, we investigate the emergence of chimera states in brain network, through inducing perturbations by stimulating brain regions. The emerged chimera states are quantified by Kuramoto order parameter and chimera index, and results show a weak and negative correlation between these two metrics.
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    Simulating Dynamics of Circulation in the Awake State and Different Stages of Sleep Using Non-autonomous Mathematical Model With Time Delay
    (Lausanne : Frontiers Research Foundation, 2021) Karavaev, Anatoly S.; Ishbulatov, Yurii M.; Prokhorov, Mikhail D.; Ponomarenko, Vladimir I.; Kiselev, Anton R.; Runnova, Anastasiia E.; Hramkov, Alexey N.; Semyachkina-Glushkovskaya, Oxana V.; Kurths, Jürgen; Penzel, Thomas
    We propose a mathematical model of the human cardiovascular system. The model allows one to simulate the main heart rate, its variability under the influence of the autonomic nervous system, breathing process, and oscillations of blood pressure. For the first time, the model takes into account the activity of the cerebral cortex structures that modulate the autonomic control loops of blood circulation in the awake state and in various stages of sleep. The adequacy of the model is demonstrated by comparing its time series with experimental records of healthy subjects in the SIESTA database. The proposed model can become a useful tool for studying the characteristics of the cardiovascular system dynamics during sleep.
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    Synaptic Plasticity in Memristive Artificial Synapses and Their Robustness Against Noisy Inputs
    (Lausanne : Frontiers Research Foundation, 2021) Du, Nan; Zhao, Xianyue; Chen, Ziang; Choubey, Bhaskar; Di Ventra, Massimiliano; Skorupa, Ilona; Bürger, Danilo; Schmidt, Heidemarie
    Emerging brain-inspired neuromorphic computing paradigms require devices that can emulate the complete functionality of biological synapses upon different neuronal activities in order to process big data flows in an efficient and cognitive manner while being robust against any noisy input. The memristive device has been proposed as a promising candidate for emulating artificial synapses due to their complex multilevel and dynamical plastic behaviors. In this work, we exploit ultrastable analog BiFeO3 (BFO)-based memristive devices for experimentally demonstrating that BFO artificial synapses support various long-term plastic functions, i.e., spike timing-dependent plasticity (STDP), cycle number-dependent plasticity (CNDP), and spiking rate-dependent plasticity (SRDP). The study on the impact of electrical stimuli in terms of pulse width and amplitude on STDP behaviors shows that their learning windows possess a wide range of timescale configurability, which can be a function of applied waveform. Moreover, beyond SRDP, the systematical and comparative study on generalized frequency-dependent plasticity (FDP) is carried out, which reveals for the first time that the ratio modulation between pulse width and pulse interval time within one spike cycle can result in both synaptic potentiation and depression effect within the same firing frequency. The impact of intrinsic neuronal noise on the STDP function of a single BFO artificial synapse can be neglected because thermal noise is two orders of magnitude smaller than the writing voltage and because the cycle-to-cycle variation of the current–voltage characteristics of a single BFO artificial synapses is small. However, extrinsic voltage fluctuations, e.g., in neural networks, cause a noisy input into the artificial synapses of the neural network. Here, the impact of extrinsic neuronal noise on the STDP function of a single BFO artificial synapse is analyzed in order to understand the robustness of plastic behavior in memristive artificial synapses against extrinsic noisy input.
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    The Search as Learning Spaceship: Toward a Comprehensive Model of Psychological and Technological Facets of Search as Learning
    (Lausanne : Frontiers Research Foundation, 2022) von Hoyer, Johannes; Hoppe, Anett; Kammerer, Yvonne; Otto, Christian; Pardi, Georg; Rokicki, Markus; Yu, Ran; Dietze, Stefan; Ewerth, Ralph; Holtz, Peter
    Using a Web search engine is one of today’s most frequent activities. Exploratory search activities which are carried out in order to gain knowledge are conceptualized and denoted as Search as Learning (SAL). In this paper, we introduce a novel framework model which incorporates the perspective of both psychology and computer science to describe the search as learning process by reviewing recent literature. The main entities of the model are the learner who is surrounded by a specific learning context, the interface that mediates between the learner and the information environment, the information retrieval (IR) backend which manages the processes between the interface and the set of Web resources, that is, the collective Web knowledge represented in resources of different modalities. At first, we provide an overview of the current state of the art with regard to the five main entities of our model, before we outline areas of future research to improve our understanding of search as learning processes.