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    A systems biology approach to analyse leaf carbohydrate metabolism in Arabidopsis thaliana
    (2011) Henkel, Sebastian; Nägele, Thomas; Hörmiller, Imke; Sauter, Thomas; Sawodny, Oliver; Ederer, Michael; Heyer, Arnd G.
    Plant carbohydrate metabolism comprises numerous metabolite interconversions, some of which form cycles of metabolite degradation and re-synthesis and are thus referred to as futile cycles. In this study, we present a systems biology approach to analyse any possible regulatory principle that operates such futile cycles based on experimental data for sucrose (Scr) cycling in photosynthetically active leaves of the model plant Arabidopsis thaliana. Kinetic parameters of enzymatic steps in Scr cycling were identified by fitting model simulations to experimental data. A statistical analysis of the kinetic parameters and calculated flux rates allowed for estimation of the variability and supported the predictability of the model. A principal component analysis of the parameter results revealed the identifiability of the model parameters. We investigated the stability properties of Scr cycling and found that feedback inhibition of enzymes catalysing metabolite interconversions at different steps of the cycle have differential influence on stability. Applying this observation to futile cycling of Scr in leaf cells points to the enzyme hexokinase as an important regulator, while the step of Scr degradation by invertases appears subordinate.
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    ItemOpen Access
    Adaptive method for quantitative estimation of glucose and fructose concentrations in aqueous solutions based on infrared nanoantenna optics
    (2019) Schuler, Benjamin; Kühner, Lucca; Hentschel, Mario; Giessen, Harald; Tarín, Cristina
    In life science and health research one observes a continuous need for new concepts and methods to detect and quantify the presence and concentration of certain biomolecules-preferably even in vivo or aqueous solutions. One prominent example, among many others, is the blood glucose level, which is highly important in the treatment of, e.g., diabetes mellitus. Detecting and, in particular, quantifying the amount of such molecular species in a complex sensing environment, such as human body fluids, constitutes a significant challenge. Surface-enhanced infrared absorption (SEIRA) spectroscopy has proven to be uniquely able to differentiate even very similar molecular species in very small concentrations. We are thus employing SEIRA to gather the vibrational response of aqueous glucose and fructose solutions in the mid-infrared spectral range with varying concentration levels down to 10 g/l. In contrast to previous work, we further demonstrate that it is possible to not only extract the presence of the analyte molecules but to determine the quantitative concentrations in a reliable and automated way. For this, a baseline correction method is applied to pre-process the measurement data in order to extract the characteristic vibrational information. Afterwards, a set of basis functions is fitted to capture the characteristic features of the two examined monosaccharides and a potential contribution of the solvent itself. The reconstruction of the actual concentration levels is then performed by superposition of the different basis functions to approximate the measured data. This software-based enhancement of the employed optical sensors leads to an accurate quantitative estimate of glucose and fructose concentrations in aqueous solutions.
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    Modeling time delay in the NFκB signaling pathway following low dose IL-1 stimulation
    (2011) Witt, Johannes; Barisic, Sandra; Sawodny, Oliver; Ederer, Michael; Kulms, Dagmar; Sauter, Thomas
    Stimulation of human epithelial cells with IL-1 (10 ng/ml) + UVB radiation results in sustained NFκB activation caused by continuous IKKbeta phosphorylation. We have recently published a strictly reduced ordinary differential equation model elucidating the involved mechanisms. Here, we compare model extensions for low IL-1 doses (0.5 ng/ml), where delayed IKKbeta phosphorylation is observed. The extended model including a positive regulatory element, most likely auto-ubiquitination of TRAF6, reproduces the observed experimental data most convincingly. The extension is shown to be consistent with the original model and contains very sensitive processes which may serve as potential intervention targets.
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    ItemOpen Access
    Regression methods for ophthalmic glucose sensing using metamaterials
    (2011) Rapp, Philipp; Mesch, Martin; Giessen, Harald; Tarín, Cristina
    We present a novel concept for in vivo sensing of glucose using metamaterials in combination with automatic learning systems. In detail, we use the plasmonic analogue of electromagnetically induced transparency (EIT) as sensor and evaluate the acquired data with support vector machines. The metamaterial can be integrated into a contact lens. This sensor changes its optical properties such as reflectivity upon the ambient glucose concentration, which allows for in situ measurements in the eye. We demonstrate that estimation errors below 2% at physiological concentrations are possible using simulations of the optical properties of the metamaterial in combination with an appropriate electrical circuitry and signal processing scheme. In the future, functionalization of our sensor with hydrogel will allow for a glucose-specific detection which is insensitive to other tear liquid substances providing both excellent selectivity and sensitivity.