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Thank you for submitting your manuscript for consideration by The EMBO Journal. It has now been seen by three referees whose comments to the authors are shown below. As you will see while all three referees consider the study as very interesting and potentially important they all feel that the causal link between cytoplasmic pH/V-ATPase and PKA needs to be(More)
Directional cell growth requires that cells read and interpret shallow chemical gradients, but how the gradient directional information is identified remains elusive. We use single-cell analysis and mathematical modeling to define the cellular gradient decoding network in yeast. Our results demonstrate that the spatial information of the gradient signal is(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)
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)
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)
BY4741 (wild-type) MATa ura3∆0; leu2∆0; his3∆1; met15∆0 Openbiosystems RD66 VMA5-GFP::HIS3 Openbiosystems RD68 VPH1-GFP::HIS3 Openbiosystems RD146 VMA5-RFP::KANR This study RD157 VMA5-RFP::KANR; VPH1-GFP::HIS3 This study RD67 VMA2-GFP::HIS3 Openbiosystems RD148 VMA5-RFP::KANR This study RD151 VMA5-RFP::KANR pHluorin::URA3 This study RD57 vma5∆::KANR(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)
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)
Robust estimation of kinetic parameters of intracellular 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)