Search

It is well-established that Whitham's modulation equations approximate the dynamics of slowly varying periodic wave trains in dispersive systems. We are interested in its validity in dissipative systems with a conservation law. The prototype example for such a system is the generalized Ginzburg-Landau system that arises as a universal amplitude system for the description of a Turing-Hopf bifurcation in spatially extended pattern-forming systems with neutrally stable long modes. In this paper we prove rigorous error estimates between the approximation obtained through Whitham's modulation equations and true solutions to this Ginzburg-Landau system. Our proof relies on analytic smoothing, Cauchy-Kovalevskaya theory, energy estimates in Gevrey spaces, and a local decomposition in Fourier space, which separates center from stable modes and uncovers a (semi)derivative in front of the relevant nonlinear terms., Comment: 24 pages, 1 figure

International audience; DNA replication is a highly regulated process that occurs in the context of chromatin structure and is sensitive to several histone post-translational modifications. In Saccharomyces cerevisiae, the histone methylase Set1 is responsible for the transcription-dependent deposition of H3K4 methylation (H3K4me) throughout the genome. Here we show that a combination of a hypomorphic replication mutation (orc5-1) with the absence of Set1 (set1Δ) compromises the progression through S-phase, and this is associated with a large increase in DNA damage. The ensuing DNA damage checkpoint activation, in addition to that of the spindle assembly checkpoint, restricts the growth of orc5-1 set1Δ. The opposite effects of the lack of RNase H activity and the reduction of histone levels on orc5-1 set1Δ viability are in agreement with their expected effects on replication fork progression. We propose that the role of H3K4 methylation during DNA replication becomes critical when the replication forks acceleration due to decreased origin firing in the orc5-1 background increases the risk for transcription replication conflicts. Furthermore, we show that an increase of reactive oxygen species levels, likely a consequence of the elevated DNA damage, is partly responsible for the lethality in orc5-1 set1Δ

Light is the primary signal that calibrates circadian neural circuits and thus coordinates daily physiological and behavioral rhythms with solar entrainment cues. Drosophila and mammalian circadian circuits consist of diverse populations of cellular oscillators that exhibit a wide range of dynamic light responses, periods, phases, and degrees of synchrony. How heterogeneous circadian circuits can generate robust physiological rhythms while remaining flexible enough to respond to synchronizing stimuli has long remained enigmatic. Cryptochrome is a short-wavelength photoreceptor that is endogenously expressed in approximately half of Drosophila circadian neurons. In a previous study, physiological light response was measured using real-time bioluminescence recordings in Drosophila whole-brain explants, which remain intrinsically light-sensitive. Here we apply analysis of real-time bioluminescence experimental data to show detailed dynamic ensemble representations of whole circadian circuit light entrainment at single neuron resolution. Organotypic whole-brain explants were either maintained in constant darkness (DD) for 6 days or exposed to a phase-advancing light pulse on the second day. We find that stronger circadian oscillators support robust overall circuit rhythmicity in DD, whereas weaker oscillators can be pushed toward transient desynchrony and damped amplitude to facilitate a new state of phase-shifted network synchrony. Additionally, we use mathematical modeling to examine how a network composed of distinct oscillator types can give rise to complex dynamic signatures in DD conditions and in response to simulated light pulses. Simulations suggest that complementary coupling mechanisms and a combination of strong and weak oscillators may enable a robust yet flexible circadian network that promotes both synchrony and entrainment. A more complete understanding of how the properties of oscillators and their signaling mechanisms facilitate their distinct roles in light entrainment may allow us to direct and augment the circadian system to speed recovery from jet lag, shift work, and seasonal affective disorder.

Alpha oscillations are modulated in response to visual temporal and spatial cues, However, the neural response to alerting cues is less explored, as is how this response is affected by healthy aging. Using scalp EEG, we examined how visual cortical alpha activity relates to working memory performance. Younger (20-30 years) and older (60-70 years) participants were presented with a visual alerting cue uninformative of the position or size of a lateralized working memory array. Older adults showed longer response times overall, and reduced accuracy when memory load was high. Older adults had less consistent cue-evoked phase resetting than younger adults, which predicted worse performance. Alpha phase prior to memory array presentation predicted response time, but the relationship between phase and response time was weaker in older adults. These results suggest that changes in alpha phase dynamics, especially prior to presentation of task-relevant stimuli, potentially contribute to age-related cognitive decline.

DNA replication is a highly regulated process that occurs in the context of chromatin structure and is sensitive to several histone post-translational modifications. In Saccharomyces cerevisiae, the histone methylase Set1 is responsible for the transcription-dependent deposition of H3K4 methylation (H3K4me) throughout the genome. Here we show that a combination of a hypomorphic replication mutation (orc5-1) with the absence of Set1 (set1Δ) compromises the progression through S phase, and this is associated with a large increase in DNA damage. The ensuing DNA damage checkpoint activation, in addition to that of the spindle assembly checkpoint, restricts the growth of orc5-1 set1Δ. Interestingly, orc5-1 set1Δ is sensitive to the lack of RNase H activity while a reduction of histone levels is able to counterbalance the loss of Set1. We propose that the recently described Set1-dependent mitigation of transcription-replication conflicts becomes critical for growth when the replication forks accelerate due to decreased origin firing in the orc5-1 background. Furthermore, we show that an increase of reactive oxygen species (ROS) levels, likely a consequence of the elevated DNA damage, is partly responsible for the lethality in orc5-1 set1Δ.Author summaryDNA replication, that ensures the duplication of the genetic material, starts at discrete sites, termed origins, before proceeding at replication forks whose progression is carefully controlled in order to avoid conflicts with the transcription of genes. In eukaryotes, DNA replication occurs in the context of chromatin, a structure in which DNA is wrapped around proteins, called histones, that are subjected to various chemical modifications. Among them, the methylation of the lysine 4 of histone H3 (H3K4) is carried out by Set1 in Saccharomyces cerevisiae, specifically at transcribed genes. We report that, when the replication fork accelerates in response to a reduction of active origins, the absence of Set1 leads to accumulation of DNA damage. Because H3K4 methylation was recently shown to slow down replication at transcribed genes, we propose that the Set1-dependent becomes crucial to limit the occurrence of conflicts between replication and transcription caused by replication fork acceleration. In agreement with this model, stabilization of transcription-dependent structures or reduction histone levels, to limit replication fork velocity, respectively exacerbates or moderates the effect of Set1 loss. Last, but not least, we show that the oxidative stress associated to DNA damage is partly responsible for cell lethality.

Background Growth differentiation factor 15 (GDF-15) in ST-elevation myocardial infarction (STEMI) is prognostic in first-generation radioimmunoassays. We examined GDF-15 temporal dynamics in STEMI and its predictive value using a first fully automated GDF-15 electrochemiluminescence assay. Methods In this prospective study, circulating GDF-15 concentration was measured at admission (0 h), 12 h and 24 h in 1026 consecutive STEMI patients treated between February 2011 and May 2016 with primary percutaneous coronary intervention. GDF-15 dynamics (0 h, 12 h, 24 h) and predictive value (30 days and 3 years) were examined. Results Median GDF-15 concentration was 1443 pg/mL at 0 h, 1731 pg/mL at 12 h and 1510 pg/mL at 24 h (p Conclusions GDF-15 peaked at 12 h and remained elevated at 24 h in STEMI. GDF-15 measurement during the first 24 h in STEMI is valuable for predicting especially short- but also long-term outcomes, and may be a useful addition to risk stratification.

Neural oscillatory dynamics are a candidate mechanism to steer perception of time and temporal rate change. While oscillator models of time perception are strongly supported by behavioral evidence, a direct link to neural oscillations and oscillatory entrainment has not yet been provided. In addition, it has thus far remained unaddressed how context-induced illusory percepts of time are coded for in oscillator models of time perception. To investigate these questions, we used magnetoencephalography and examined the neural oscillatory dynamics that underpin pitch-induced illusory percepts of temporal rate change. Human participants listened to frequency-modulated sounds that varied over time in both modulation rate and pitch, and judged the direction of rate change (decrease vs increase). Our results demonstrate distinct neural mechanisms of rate perception: Modulation rate changes directly affected listeners' rate percept as well as the exact frequency of the neural oscillation. However, pitch-induced illusory rate changes were unrelated to the exact frequency of the neural responses. The rate change illusion was instead linked to changes in neural phase patterns, which allowed for single-trial decoding of percepts. That is, illusory underestimations or overestimations of perceived rate change were tightly coupled to increased intertrial phase coherence and changes in cerebro-acoustic phase lag. The results provide insight on how illusory percepts of time are coded for by neural oscillatory dynamics.

Polymer characterizations are often performed using mass spectrometry (MS). Aside from MS and different tandem MS (MS/MS) techniques, ion mobility–mass spectrometry (IM-MS) has been recently added to the inventory of characterization technique. However, only few studies have focused on the reproducibility and robustness of polymer IM-MS analyses. Here, we perform collisional and electron-mediated activation of polymer ions before measuring IM drift times, collision cross-sections (CCS), or reduced ion mobilities (K0). The resulting IM behavior of different activated product ions is then compared to non-activated native intact polymer ions. First, we analyzed collision induced unfolding (CIU) of precursor ions to test the robustness of polymer ion shapes. Then, we focused on fragmentation product ions to test for shape retentions from the precursor ions: cation ejection species (CES) and product ions with m/z and charge state values identical to native intact polymer ions. The CES species are formed using both collision induced dissociation (CID) and electron transfer dissociation (ETD, formally ETnoD) experiments. Only small drift time, CCS, or K0 deviations between the activated/formed ions are observed compared to the native intact polymer ions. The polymer ion shapes seem to depend solely on their mass and charge state. The experiments were performed on three synthetic homopolymers: poly(ethoxy phosphate) (PEtP), poly(2-n-propyl-2-oxazoline) (Pn-PrOx), and poly(ethylene oxide) (PEO). These results confirm the robustness of polymer ion CCSs for IM calibration, especially singly charged polymer ions. The results are also discussed in the context of polymer analyses, CCS predictions, and probing ion–drift gas interaction potentials.

Materials 10(2), 208 (2017). doi:10.18154/RWTH-2017-03760, Published by MDPI, Basel

Partial synchronous states appear between full synchrony and asynchrony and exhibit many interesting properties. Most frequently, these states are studied within the framework of phase approximation. The latter is used ubiquitously to analyze coupled oscillatory systems. Typically, the phase dynamics description is obtained in the weak coupling limit, i.e., in the first-order in the coupling strength. The extension beyond the first-order represents an unsolved problem and is an active area of research. In this paper, three partially synchronous states are investigated and presented in order of increasing complexity. First, the usage of the phase response curve for the description of macroscopic oscillators is analyzed. To achieve this, the response of the mean-field oscillations in a model of all-to-all coupled limit-cycle oscillators to pulse stimulation is measured. The next part treats a two-group Kuramoto model, where the interaction of one attractive and one repulsive group results in an interesting solitary state, situated between full synchrony and self-consistent partial synchrony. In the last part, the phase dynamics of a relatively simple system of three Stuart-Landau oscillators are extended beyond the weak coupling limit. The resulting model contains triplet terms in the high-order phase approximation, though the structural connections are only pairwise. Finally, the scaling of the new terms with the coupling is analyzed., Comment: 16 pages, 6 figures

In this study we develop a computational framework for the reconstruction of phase dynamics in spatio-temporally oscillating systems and use it to study the dynamics of the somitogenesis clock oscillator. Our understanding of the somitogenesis clock, a developmental oscillator found in the vertebrate embryo, has been revolutionised by the development of real time reporters of clock gene expression. However, the signals obtained from the real time reporters are typically noisy, nonstationary and spatiotemporally dynamic and there are open questions with regard to how post-processing can be used to both improve the insight gained from a given experiment and to constrain theoretical models. In this study we present a methodology, which is a variant of empirical mode decomposition, that reconstructs the phase dynamics of the somitogenesis clock. After validating the methodology using synthetic datasets, we define a set of metrics that use the reconstructed phase profiles to infer biologically meaningful quantities. We perform experiments that measure signal from a real time reporter of the somitogenesis clock and reconstruct the phase dynamics. Application of the defined metrics yields results that are consistent with previous experimental observations. Moreover, we extend previous work by developing a gradient descent method for defining unbiased kymographs and showing that boundary conditions are nonhomogeneous. By studying phase dynamics along phase gradient descent trajectories, we show that, consistent with a previous theoretical model, the oscillation frequency is inversely correlated with the phase gradient but that the coefficient is not constant in time. The proposed methodology provides a tool kit for that can be used in the analysis of future experiments and the quantitative observations can be used to guide the development of future mathematical models.

[EN] The microstructure of rubber-modified polystyrene after thermal ageing at 90 °C and multiple extrusion was analyzed by time-domain nuclear magnetic resonance (TD-NMR) in a non-destructive manner. The transverse magnetization decay behaviour observed in TD-NMR was related to the total rubber fraction and its cross-linking density. The data reveal different mechanisms of long-term rubber degradation in high-impact polystyrene (HIPS) during thermo-oxidation and multiple processing: Multiple processing causes a slight increase in the cross-linking density of the rubber phase, without appreciably altering the total amount of rubber fraction. Thermo-oxidation is accompanied by a significant overall decrease of the rubber fraction, an increase of the cross-linking density, and a pronounced increase of the non-crosslinked fraction (chain ends and fragmented segments). The NMR results correlate well with spectroscopic observations and moderately with macroscopic mechanical properties. © 2011 Elsevier Ltd. All rights reserved., The lab support for the NMR studies by Jens Schober and Cornelia Willax is gratefully acknowledged. FV thanks the economical support of the Spanish Ministry of Science and Innovation through the FPU doctoral program.

The melting of an ultrathin lubricant film is studied at friction between atomically flat surfaces. We take into account fluctuations of lubricant temperature, which are defined by the Ornstein-Uhlenbeck process. Phase diagrams and portraits are calculated for second- and first-order transitions (the melting of an amorphous and that of a crystalline lubricants, respectively). It is shown that, in the former case, a stick-slip friction domain, separating the regions of dry and sliding friction, appears. In the latter case, three domains of stick-slip friction arise, which are characterized by the transitions between dry, metastable and stable sliding friction. The increase in the correlation time of lubricant temperature fluctuations leads to increasing in the rubbing-surface temperature needed for realization of sliding friction. The stationary states, corresponding to dry, stable and metastable sliding friction, are reached as a result of damped oscillations.

The melting of an ultrathin lubricant film at friction between atomically smooth surfaces is studied with allowance for fluctuations of its temperature, which are described by the Ornstein-Uhlenbeck process. The behavior of the most probable types of shear stresses arising in the lubricant is considered, and phase diagrams for second- and first-order phase transformations (the melting of an amorphous lubricant and that of a crystal- line lubricant, respectively) are constructed. It is shown that, in the former case, lubricant temperature fluctua- tions lead to the formation of a stick-slip friction domain separating the domains of dry and sliding friction, which is typical of first-order transitions. In the latter case, three domains of stick-slip friction arise, which mark the transitions between dry friction and metastable and stable sliding friction. As the time of correlation of lubricant temperature fluctuations gets longer, the temperature of rubbing surfaces rises to the point where sliding friction sets in.

We consider a singular phase field system located in a smooth bounded domain. In the entropy balance equation appears a logarithmic nonlinearity. The second equation of the system, deduced from a balance law for the microscopic forces that are responsible for the phase transition process, is perturbed by an additional term involving a possibly nonlocal maximal monotone operator and arising from a class of sliding mode control problems. We prove existence and uniqueness of the solution for this resulting highly nonlinear system. Moreover, under further assumptions, the longtime behavior of the solution is investigated.

The formation of spatially repetitive structures along the growth axis of a developing embryo is a common theme in developmental biology. Here we apply the novel flow-distributed oscillator (FDO) mechanism of wave pattern formation to the problem of axial segmentation in general and to somitogenesis in particular. We argue that the conditions for formation of FDO waves are satisfied during somitogenesis in the chick and mouse and that the waves of gene expression observed in these species arise from phase dynamics in a growing oscillatory medium. We substantiate this claim by showing that the FDO mechanism allows the waves to be mimicked by an inorganic experiment and that it predicts a wavelength that coincides with that observed experimentally. To see whether the FDO mechanism is compatible with other aspects of somitogenesis, we construct an FDO-based model of somitogenesis and successfully test it against a number of experimental observations, including the effect of heat shock. Our analysis provides a rigorous physical basis for the hypothesis that the phase dynamics of a segmental clock controls important stages of segmentation during somitogenesis in the chick and mouse as well as in other organisms that undergo segmentation during their axial growth.

Using the previous approach outlined in Ratliff and Bridges (2016, 2015), a novel method is presented to derive the fifth order Kadomtsev–Petviashvili(KP) equation from periodic wavetrains. As a result, the coefficients and criterion for the fifth order KP to emerge take a universal form that can be determined a-priori, relating to the system’s conservation laws and the termination of a Jordan chain. Moreover, the analysis reveals that generically a mixed dispersive term q X X X Y appears within the final phase equation. The theory presented here is complimented by an example from the context of flexural gravity waves in shallow water and a higher order Nonlinear Schrodinger model relevant in plasma physics, demonstrating how the coefficients in this model are determined via elementary calculations.

International audience; Protonated intermediates are postulated to be involved in the rate determining step of many sugar reactions. This paper presents a study of protonated sugar species, isolated in the gas phase, using a combination of infrared multiple photon dissociation (IRMPD) spectroscopy, classical ab initio molecular dynamics (AIMD) and quantum mechanical vibrational self-consistent field (VSCF) calculations. It provides a likely identification of the reactive intermediate oxocarbenium ion structure in a D-galactosyl system as well as the saccharide pyrolysis product anhydrogalactose (that suggests oxocarbenium ion stabilization), along with the spectrum of the protonated parent species: methyl D-galactopyranoside-H +. Its vibrational fingerprint indicates intramolecular proton sharing. Classical AIMD simulations for galactosyl oxocarbenium ions, conducted in the temperature range ~300-350 K (using B3LYP potentials on-the-fly) reveal efficient transitions on the picosecond timescale. Multiple conformers are likely to exist under the experimental conditions and along with static VSCF calculations, they have facilitated the identification of the individual structural motifs of the galactosyl oxocarbenium ion and protonated anhydrogalactose ion conformers that contribute to the observed experimental spectra. These results demonstrate the power of experimental IRMPD spectroscopy combined with dynamics simulations and with computational spectroscopy at the anharmonic level to unravel conformer structures of protonated saccharides, and to provide information on their lifetimes.

Cell viability and cytotoxicity assays are highly important for drug screening and cytotoxicity tests of antineoplastic or other therapeutic drugs. Even though biochemical-based tests are very helpful to obtain preliminary preview, their results should be confirmed by methods based on direct cell death assessment. In this study, time-dependent changes in quantitative phase-based parameters during cell death were determined and methodology useable for rapid and label-free assessment of direct cell death was introduced. The goal of our study was distinction between apoptosis and primary lytic cell death based on morphologic features. We have distinguished the lytic and non-lytic type of cell death according to their end-point features (Dance of Death typical for apoptosis versus swelling and membrane rupture typical for all kinds of necrosis common for necroptosis, pyroptosis, ferroptosis and accidental cell death). Our method utilizes Quantitative Phase Imaging (QPI) which enables the time-lapse observation of subtle changes in cell mass distribution. According to our results, morphological and dynamical features extracted from QPI micrographs are suitable for cell death detection (76% accuracy in comparison with manual annotation). Furthermore, based on QPI data alone and machine learning, we were able to classify typical dynamical changes of cell morphology during both caspase 3,7-dependent and -independent cell death subroutines. The main parameters used for label-free detection of these cell death modalities were cell density (pg/pixel) and average intensity change of cell pixels further designated as Cell Dynamic Score (CDS). To the best of our knowledge, this is the first study introducing CDS and cell density as a parameter typical for individual cell death subroutines with prediction accuracy 75.4% for caspase 3,7-dependent and -independent cell death.

The study of hyperbolic waves involves various notions which help characterise how these structures evolve. One important facet is the notion of \emph{genuine nonlinearity}, namely the ability for shocks and rarefactions to form instead of contact discontinuities. In the context of the Whitham Modulation equations, this paper demonstrate that a loss of genuine nonlinearity leads to the appearance of a dispersive set of dynamics in the form of the modified Korteweg de-Vries equation governing the evolution of the waves instead. Its form is universal in the sense that its coefficients can be written entirely using linear properties of the underlying waves such as the conservation laws and linear dispersion relation. This insight is applied to two systems of physical interest, one an optical model and the other a stratified hydrodynamics experiment, to demonstrate how it can be used to provide insight into how waves in these systems evolve when genuine nonlinearity is lost., Comment: 38 pages