Synthetic LISA: Simulating Time Delay Interferometry in a Model LISA

We report on three numerical experiments on the implementation of Time-Delay Interferometry (TDI) for LISA, performed with Synthetic LISA, a C++/Python package that we developed to simulate the LISA science process at the level of scientific and technical requirements. Specifically, we study the laser-noise residuals left by first-generation TDI when the LISA armlengths have a realistic time dependence; we characterize the armlength-measurements accuracies that are needed to have effective laser-noise cancellation in both first- and second-generation TDI; and we estimate the quantization and telemetry bitdepth needed for the phase measurements. Synthetic LISA generates synthetic time series of the LISA fundamental noises, as filtered through all the TDI observables; it also provides a streamlined module to compute the TDI responses to gravitational waves according to a full model of TDI, including the motion of the LISA array and the temporal and directional dependence of the armlengths. We discuss the theoretical model that underlies the simulation, its implementation, and its use in future investigations on system characterization and data-analysis prototyping for LISA.Comment: 18 pages, 14 EPS figures, REVTeX 4. Accepted PRD version. See http://www.vallis.org/syntheticlisa for information on the Synthetic LISA software packag

Study of wound healing dynamics by single pseudo-particle tracking in phase contrast images acquired in time-lapse

Cellular contacts modify the way cells migrate in a cohesive group with respect to a free single cell. The resulting motion is persistent and correlated, with cells’ velocities self-aligning in time. The presence of a dense agglomerate of cells makes the application of single particle tracking techniques to define cells dynamics difficult, especially in the case of phase contrast images. Here, we propose an original pipeline for the analysis of phase contrast images of the wound healing scratch assay acquired in time-lapse, with the aim of extracting single particle trajectories describing the dynamics of the wound closure. In such an approach, the membrane of the cells at the border of the wound is taken as a unicum, i.e., the wound edge, and the dynamics is described by the stochastic motion of an ensemble of points on such a membrane, i.e., pseudo-particles. For each single frame, the pipeline of analysis includes: first, a texture classification for separating the background from the cells and for identifying the wound edge; second, the computation of the coordinates of the ensemble of pseudo-particles, chosen to be uniformly distributed along the length of the wound edge. We show the results of this method applied to a glioma cell line (T98G) performing a wound healing scratch assay without external stimuli. We discuss the efficiency of the method to assess cell motility and possible applications to other experimental layouts, such as single cell motion. The pipeline is developed in the Python language and is available upon request

Study of Wound Healing Dynamics by Single Pseudo-Particle Tracking in Phase Contrast Images Acquired in Time-Lapse

Cellular contacts modify the way cells migrate in a cohesive group with respect to a free single cell. The resulting motion is persistent and correlated, with cells’ velocities self-aligning in time. The presence of a dense agglomerate of cells makes the application of single particle tracking techniques to define cells dynamics difficult, especially in the case of phase contrast images. Here, we propose an original pipeline for the analysis of phase contrast images of the wound healing scratch assay acquired in time-lapse, with the aim of extracting single particle trajectories describing the dynamics of the wound closure. In such an approach, the membrane of the cells at the border of the wound is taken as a unicum, i.e., the wound edge, and the dynamics is described by the stochastic motion of an ensemble of points on such a membrane, i.e., pseudo-particles. For each single frame, the pipeline of analysis includes: first, a texture classification for separating the background from the cells and for identifying the wound edge; second, the computation of the coordinates of the ensemble of pseudo-particles, chosen to be uniformly distributed along the length of the wound edge. We show the results of this method applied to a glioma cell line (T98G) performing a wound healing scratch assay without external stimuli. We discuss the efficiency of the method to assess cell motility and possible applications to other experimental layouts, such as single cell motion. The pipeline is developed in the Python language and is available upon request.Basque Government BERC 2018– 2021 Spanish Ministry of Economy and Competitiveness MINECO via the BCAM Severo Ochoa SEV-2017-0718 accreditatio

Network Entropy measures applied to different systemic perturbations of cell basal state

NOTE: includes supplementary materialNOTE: includes supplementary materialNOTE: includes supplementary materialWe characterize different cell states, related to cancer and ageing phenotypes, by a measure of entropy of network ensembles, integrating gene expression values and protein interaction networks. The entropy measure estimates the parameter space available to the network ensemble, that can be interpreted as the level of plasticity of the system for high entropy values (the ability to change its internal parameters, e.g. in response to environmental stimuli), or as a fine tuning of the parameters (that restricts the range of possible parameter values) in the opposite case. This approach can be applied at different scales, from whole cell to single biological functions, by defining appropriate subnetworks based on a priori biological knowledge, thus allowing a deeper understanding of the cell processes involved. In our analysis we used specific network features (degree sequence, subnetwork structure and distance between gene profiles) to obtain informations at different biological scales, providing a novel point of view for the integration of experimental transcriptomic data and a priori biological knowledge, but the entropy measure can also highlight other aspects of the biological systems studied depending on the constraints introduced in the model (e.g. community structures)

Stochastic analysis of a miRNA-protein toggle switch

none5Within systems biology there is an increasing interest in the stochastic behavior of genetic and biochemical reaction networks. An appropriate stochastic description is provided by the chemical master equation, which represents a continuous time Markov chain (CTMC). In this paper we consider the stochastic properties of a toggle switch, involving a protein compound (E2Fs and Myc) and a miRNA cluster (miR-17-92), known to control the eukaryotic cell cycle and possibly involved in oncogenesis, recently proposed in the literature within a deterministic framework. Due to the inherent stochasticity of biochemical processes and the small number of molecules involved, the stochastic approach should be more correct in describing the real system: we study the agreement between the two approaches by exploring the system parameter space. We address the problem by proposing a simplified version of the model that allows analytical treatment, and by performing numerical simulations for the full model. We observed optimal agreement between the stochastic and the deterministic description of the circuit in a large range of parameters, but some substantial differences arise in at least two cases: (1) when the deterministic system is in the proximity of a transition from a monostable to a bistable configuration, and (2) when bistability (in the deterministic system) is "masked" in the stochastic system by the distribution tails. The approach provides interesting estimates of the optimal number of molecules involved in the toggle switch. Our discussion of the points of strengths, potentiality and weakness of the chemical master equation in systems biology and the differences with respect to deterministic modeling are leveraged in order to provide useful advice for both the bioinformatician and the theoretical scientist.openGiampieri E.; Remondini D.; de Oliveira L.; Castellani G.; Lió P.Giampieri E.; Remondini D.; de Oliveira L.; Castellani G.; Lió P

Large-scale modelling of neuronal systems

The brain is, without any doubt, the most complex system of the human body. Its complexity is also due to the extremely high number of neurons, as well as the huge number of synapses connecting them. Each neuron is capable to perform complex tasks, like learning and memorizing a large class of patterns. The simulation of large neuronal systems is challenging for both technological and computational reasons, and can open new perspectives for the comprehension of brain functioning. A well-known and widely accepted model of bidirectional synaptic plasticity, the BCM model, is stated by a differential equation approach based on bistability and selectivity properties. We have modified the BCM model extending it from a single-neuron to a whole-network model. This new model is capable to generate interesting network topologies starting from a small number of local parameters, describing the interaction between incoming and outgoing links from each neuron. We have characterized this model in terms of complex network theory, showing how this learning rule can be a support for network generation

A fully automated pipeline for a robust conjunctival hyperemia estimation

Purpose: Many semi-automated and fully-automated approaches have been proposed in literature to improve the objectivity of the estimation of conjunctival hyperemia, based on image processing analysis of eyes’ photographs. The purpose is to improve its evaluation using faster fully-automated systems and independent by the human subjectivity. Methods: In this work, we introduce a fully-automated analysis of the redness grading scales able to completely automatize the clinical procedure, starting from the acquired image to the redness estimation. In particular, we introduce a neural network model for the conjunctival segmentation followed by an image processing pipeline for the vessels network segmentation. From these steps, we extract some features already known in literature and whose correlation with the conjunctival redness has already been proved. Lastly, we implemented a predictive model for the conjunctival hyperemia using these features. Results: In this work, we used a dataset of images acquired during clinical practice.We trained a neural network model for the conjunctival segmentation, obtaining an average accuracy of 0.94 and a corresponding IoU score of 0.88 on a test set of images. The set of features extracted on these ROIs is able to correctly predict the Efron scale values with a Spearman’s correlation coefficient of 0.701 on a set of not previously used samples. Conclusions: The robustness of our pipeline confirms its possible usage in a clinical practice as a viable decision support system for the ophthalmologists