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Glucose is the preferred carbon source for most cell types and a major determinant of cell growth. In yeast and certain mammalian cells, glucose activates the cAMP-dependent protein kinase A (PKA), but the mechanisms of PKA activation remain unknown. Here, we identify cytosolic pH as a second messenger for glucose that mediates activation of the PKA pathway(More)
Mitogen-activated protein kinase (MAPK) cascades are conserved signaling modules that control many cellular processes by integrating intra- and extracellular cues. The p38/Hog1 MAPK is transiently activated in response to osmotic stress, leading to rapid translocation into the nucleus and induction of a specific transcriptional program. When investigating(More)
Spectral resolved tissue imaging has a broad range of biomedical applications such as the minimally invasive diagnosis of diseases and the study of wound healing and tissue engineering processes. Two-photon microscopy imaging of endogenous fluorescence has been shown to be a powerful method for the quantification of tissue structure and biochemistry. While(More)
Recent computational studies indicate that the molecular noise of a cellular process may be a rich source of information about process dynamics and parameters. However, accessing this source requires stochastic models that are usually difficult to analyze. Therefore, parameter estimation for stochastic systems using distribution measurements, as provided(More)
— Robust estimation of kinetic parameters of intra-cellular processes requires large amounts of quantitative data. Due to the high uncertainty of such processes and the fact that recent single-cell measurement techniques have limited resolution and dimensionality, estimation should pool recordings of multiple cells of an isogenic cell population. However,(More)
— Calibration or model parameter estimation from measured data is an ubiquitous problem in engineering. In systems biology this problem turns out to be particularly challenging due to very short data-records, low signal-to-noise ratio of data acquisition, large intrinsic process noise and limited measurement access to only a few, of sometimes several(More)
Parameterized models of biophysical and mechanical cell properties are important for predictive mathematical modeling of cellular processes. The concepts of turgor, cell wall elasticity, osmotically active volume, and intracellular osmolarity have been investigated for decades, but a consistent rigorous parameterization of these concepts is lacking. Here,(More)
The NarI sequence represents a strong mutation hot spot for -2 frameshift mutations induced by N-2-acetylaminofluorene (AAF), a strong chemical carcinogen. Only when bound to the third (underlined) guanine (5'-GGCGCC-->GGCC) can AAF trigger frameshift mutations, suggesting the involvement of a slipped replication intermediate with a two-nucleotide bulge.(More)
The measurement of Forster resonance energy transfer (FRET) in microscopes can be realized by different imaging modalities. In the present work, reference FRET constructs are developed to allow the comparison of FRET microscopy measurements using intensity, spectral, and lifetime imaging. Complimentary DNA strands are respectively labeled with Oregon Green(More)
Mathematical methods combined with measurements of single-cell dynamics provide a means to reconstruct intracellular processes that are only partly or indirectly accessible experimentally. To obtain reliable reconstructions, the pooling of measurements from several cells of a clonal population is mandatory. However, cell-to-cell variability originating from(More)