Complex delay dynamics on railway networks: from universal laws to realistic modelling

Railways are a key infrastructure for any modern country. The reliability and resilience of this peculiar transportation system may be challenged by different shocks such as disruptions, strikes and adverse weather conditions. These events compromise the correct functioning of the system and trigger the spreading of delays into the railway network on a daily basis. Despite their importance, a general theoretical understanding of the underlying causes of these disruptions is still lacking. In this work, we analyse the Italian and German railway networks by leveraging on the train schedules and actual delay data retrieved during the year 2015. We use {these} data to infer simple statistical laws ruling the emergence of localized delays in different areas of the network and we model the spreading of these delays throughout the network by exploiting a framework inspired by epidemic spreading models. Our model offers a fast and easy tool for the preliminary assessment of the {effectiveness of} traffic handling policies, and of the railway {network} criticalities.Comment: 32 pages (with appendix), 28 Figures (with appendix), 2 Table

Shrinking Point Bifurcations of Resonance Tongues for Piecewise-Smooth, Continuous Maps

Resonance tongues are mode-locking regions of parameter space in which stable periodic solutions occur; they commonly occur, for example, near Neimark-Sacker bifurcations. For piecewise-smooth, continuous maps these tongues typically have a distinctive lens-chain (or sausage) shape in two-parameter bifurcation diagrams. We give a symbolic description of a class of "rotational" periodic solutions that display lens-chain structures for a general $N$-dimensional map. We then unfold the codimension-two, shrinking point bifurcation, where the tongues have zero width. A number of codimension-one bifurcation curves emanate from shrinking points and we determine those that form tongue boundaries.Comment: 27 pages, 6 figure

Inference of gene regulatory networks and compound mode of action from time course gene expression profiles.

MOTIVATION: Time series expression experiments are an increasingly popular method for studying a wide range of biological systems. Here we developed an algorithm that can infer the local network of gene-gene interactions surrounding a gene of interest. This is achieved by a perturbation of the gene of interest and subsequently measuring the gene expression profiles at multiple time points. We applied this algorithm to computer simulated data and to experimental data on a nine gene network in Escherichia coli. RESULTS: In this paper we show that it is possible to recover the gene regulatory network from a time series data of gene expression following a perturbation to the cell. We show this both on simulated data and on a nine gene subnetwork part of the DNA-damage response pathway (SOS pathway) in the bacteria E. coli

Automatic synchronisation of the cell cycle in budding yeast through closed-loop feedback control

The cell cycle is the process by which eukaryotic cells replicate. Yeast cells cycle asynchronously with each cell in the population budding at a different time. Although there are several experimental approaches to synchronise cells, these usually work only in the short-term. Here, we build a cyber-genetic system to achieve long-term synchronisation of the cell population, by interfacing genetically modified yeast cells with a computer by means of microfluidics to dynamically change medium, and a microscope to estimate cell cycle phases of individual cells. The computer implements a controller algorithm to decide when, and for how long, to change the growth medium to synchronise the cell-cycle across the population. Our work builds upon solid theoretical foundations provided by Control Engineering. In addition to providing an avenue for yeast cell cycle synchronisation, our work shows that control engineering can be used to automatically steer complex biological processes towards desired behaviours similarly to what is currently done with robots and autonomous vehicles

Priming attachment security and outgroup humanization: The mediation role of intergroup emotions

Individuals tend to dehumanize the outgroup. In this paper, we explore whether the activation of attachment security can attenuate dehumanization. Two studies were performed. In Study 1, attachment security was primed by showing pictures that depicted relationships with attachment figures; the outgroup was the homeless and humanization was measured considering the attribution of uniquely human and non-uniquely human emotions to this group. In Study 2, the sense of interpersonal security was activated by inviting participants to relive a recent interaction that left them with a feeling of safety and warmth. Outgroup members were the Roma, and humanization was measured considering the attribution of uniquely human and human nature traits to them. In Study 2, the mediation effect of intergroup emotions was investigated. In both studies, outgroup humanization effects were highlighted. In Study 2, these effects were mediated by increased empathy toward the outgroup. Interestingly, the positive impact of security activation was not moderated by chronic attachment orientations. Findings suggest strategies that can be used to improve intergroup relations in specific contexts and in society at large

Quantitative Characterization of α-Synuclein Aggregation in Living Cells through Automated Microfluidics Feedback Control

Aggregation of α-synuclein and formation of inclusions are hallmarks of Parkinson's disease (PD). Aggregate formation is affected by cellular environment, but it has been studied almost exclusively in cell-free systems. We quantitatively analyzed α-synuclein inclusion formation and clearance in a yeast cell model of PD expressing either wild-type (WT) α-synuclein or the disease-associated A53T mutant from the galactose (Gal)-inducible promoter. A computer-controlled microfluidics device regulated α-synuclein in cells by means of closed-loop feedback control. We demonstrated that inclusion formation is strictly concentration dependent and that the aggregation threshold of the A53T mutant is about half of the WT α-synuclein (56%). We chemically modulated the proteasomal and autophagic pathways and demonstrated that autophagy is the main determinant of A53T α-synuclein inclusions’ clearance. In addition to proposing a technology to overcome current limitations in dynamically regulating protein expression levels, our results contribute to the biology of PD and have relevance for therapeutic applications

Simultaneous Border-Collision and Period-Doubling Bifurcations

We unfold the codimension-two simultaneous occurrence of a border-collision bifurcation and a period-doubling bifurcation for a general piecewise-smooth, continuous map. We find that, with sufficient non-degeneracy conditions, a locus of period-doubling bifurcations emanates non-tangentially from a locus of border-collision bifurcations. The corresponding period-doubled solution undergoes a border-collision bifurcation along a curve emanating from the codimension-two point and tangent to the period-doubling locus here. In the case that the map is one-dimensional local dynamics are completely classified; in particular, we give conditions that ensure chaos.Comment: 22 pages; 5 figure

Identification and characterization of PlAlix, the Alix homologue from the Mediterranean sea urchin Paracentrotus lividus.

The sea urchin provides a relatively simple and tractable system for analyzing the early stages of embryo development. Here, we use the sea urchin species, Paracentrotus lividus, to investigate the role of Alix in key stages of embryogenesis, namely the egg fertilization and the first cleavage division. Alix is a multifunctional protein involved in different cellular processes including endocytic membrane trafficking, filamentous (F)-actin remodeling, and cytokinesis. Alix homologues have been identified in different metazoans; in these organisms, Alix is involved in oogenesis and in determination/differentiation events during embryo development. Herein, we describe the identification of the sea urchin homologue of Alix, PlAlix. The deduced amino acid sequence shows that Alix is highly conserved in sea urchins. Accordingly, we detect the PlAlix protein cross-reacting with monoclonal Alix antibodies in extracts from P. lividus, at different developmental stages. Focusing on the role of PlAlix during early embryogenesis we found that PlAlix is a maternal protein that is expressed at increasingly higher levels from fertilization to the 2-cell stage embryo. In sea urchin eggs, PlAlix localizes throughout the cytoplasm with a punctuated pattern and, soon after fertilization, accumulates in larger puncta in the cytosol, and in microvilli-like protrusions. Together our data show that PlAlix is structurally conserved from sea urchin to mammals and may open new lines of inquiry into the role of Alix during the early stages of embryo development

A single-cell analysis of breast cancer cell lines to study tumour heterogeneity and drug response

Cancer cells within a tumour have heterogeneous phenotypes and exhibit dynamic plasticity. How to evaluate such heterogeneity and its impact on outcome and drug response is still unclear. Here, we transcriptionally profile 35,276 individual cells from 32 breast cancer cell lines to yield a single cell atlas. We find high degree of heterogeneity in the expression of biomarkers. We then train a deconvolution algorithm on the atlas to determine cell line composition from bulk gene expression profiles of tumour biopsies, thus enabling cell line-based patient stratification. Finally, we link results from large-scale in vitro drug screening in cell lines to the single cell data to computationally predict drug responses starting from single-cell profiles. We find that transcriptional heterogeneity enables cells with differential drug sensitivity to co-exist in the same population. Our work provides a framework to determine tumour heterogeneity in terms of cell line composition and drug response