Morphoelastic modelling of pattern development in the petal epidermal cell cuticle.

We use the model system Hibiscus trionum as a vehicle to study the origin and propagation of surface nano-ridges in plant petal epidermal cells by tracking the development of the cell shape and the cuticle. In this system, the cuticle develops two distinct sub-layers, (i) an uppermost layer which increases in thickness and in-plane extension and (ii) a substrate, composed of cuticular and cell wall material. We quantify the pattern formation and geometrical changes and then postulate a mechanical model assuming that the cuticle behaves as a growing bi-layer. The model is a quasi-static morphoelastic system and it is numerically investigated in two- and three-dimensional settings, using different laws of film and substrate expansion and boundary conditions. We recreate several features of the observed developmental trajectories in petals. We establish the respective roles of the layers' stiffness mismatch, the underlying cell-wall curvature, the cell in-plane expansion and the thickness growth rates of the layers in determining the observed pattern features, such as the variance observed in the amplitude and wavelength of the cuticular striations. Our observations provide evidence which justifies the growing bi-layer description, and provide valuable insights into why some systems develop surface patterns and others do not.

A Typical Workflow to Simulate Cytoskeletal Systems.

Many cytoskeletal systems are now sufficiently well known to permit their precise quantitative modeling. Microtubule and actin filaments are well characterized, and the associated proteins are often known, as well as their abundance and the interactions between these elements. Thus, computer simulations can be used to investigate the collective behavior of the system precisely, in a way that is complementary to experiments. Cytosim is an Open Source cytoskeleton simulation suite designed to handle large systems of flexible filaments with associated proteins such as molecular motors. It also offers the possibility to simulate passive crosslinkers, diffusible crosslinkers, nucleators, cutters, and discrete versions of the motors that only step on unoccupied lattice sites on a filament. Other objects complement the filaments by offering spherical or more complicated geometry that can be used to represent chromosomes, the nucleus, or vesicles in the cell. Cytosim offers simple command-line tools for running a simulation and displaying its results, which are versatile and do not require programming skills. In this workflow, step-by-step instructions are given to i) install the necessary environment on a new computer, ii) configure Cytosim to simulate the contraction of a 2D actomyosin network, and iii) produce a visual representation of the system. Next, the system is probed by systematically varying a key parameter: the number of crosslinkers. Finally, the visual representation of the system is complemented by the numerical quantification of contractility to view, in a graph, how contractility depends on the composition of the system. Overall, these different steps constitute a typical workflow that can be applied with few modifications to tackle many other problems in the cytoskeletal field.

Mechanical buckling can pattern the light-diffracting cuticle of Hibiscus trionum.

Many species have cuticular striations that play a range of roles, from pollinator attraction to surface wettability. In Hibiscus trionum, the striations span multiple cells at the base of the petal to form a pattern that produces a type of iridescence. It is postulated, using theoretical models, that the pattern of striations could result from mechanical instabilities. By combining the application of mechanical stress with high-resolution imaging, we demonstrate that the cuticle buckles to create a striated pattern. Through mechanical modeling and cryo-SEM fractures, we show that the cuticle behaves like a bilayer system with a stiff film on a compliant substrate. The pattern of buckling aligns with the direction of the stress to create a larger-scale pattern. Our findings contribute to the understanding of the formation of tissue-wide patterns in living organisms.

Effects of Lean Healthcare on Patient Flow: A Systematic Review.

OBJECTIVES: To assess the effects of lean healthcare (LH) on patient flow in ambulatory care and determine whether waiting time and length of stay (LOS) decrease after LH interventions. METHODS: A systematic review was performed with close adherence to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We searched for studies of healthcare organizations applying LH interventions within ambulatory care published between 2002 and 2018. Six databases and grey literature sources were used. Two reviewers independently screened and assessed each study. When consensus was difficult to reach, a third reviewer intervened. Finally, a summary of findings was generated. RESULTS: Out of 5627 studies, 40 were included. Regarding LOS for all patients, 19 out of 22 studies reported a decrease. LOS for discharged patients decreased in 11 out of 13 studies, whereas LOS for admitted patients was reduced in 6 out of 7 studies. Waiting time for patients before seeing a healthcare professional decreased in 24 out of 26 studies. Waiting time to treatment and waiting time for appointments were minimized in 4 and 2 studies, respectively. Patients who left without being seen by a doctor decreased in 9 out of 12 studies. Finally, patient and staff satisfaction were measured in 8 and 2 studies, respectively, with each reporting improvements. CONCLUSIONS: According to our findings, LH helped to reduce waiting time and LOS in ambulatory care, mainly owing to its focus on identifying and minimizing non-value added (NVA) activities. Nevertheless, evidence of the impact of LH on patient/staff satisfaction and the translation of the obtained benefits into savings is scarce among studies.

Lessons from Fraxinus, a crowd-sourced citizen science game in genomics.

In 2013, in response to an epidemic of ash dieback disease in England the previous year, we launched a Facebook-based game called Fraxinus to enable non-scientists to contribute to genomics studies of the pathogen that causes the disease and the ash trees that are devastated by it. Over a period of 51 weeks players were able to match computational alignments of genetic sequences in 78% of cases, and to improve them in 15% of cases. We also found that most players were only transiently interested in the game, and that the majority of the work done was performed by a small group of dedicated players. Based on our experiences we have built a linear model for the length of time that contributors are likely to donate to a crowd-sourced citizen science project. This model could serve a guide for the design and implementation of future crowd-sourced citizen science initiatives.

Are SR Ca content fluctuations or SR refractoriness the key to atrial cardiac alternans?: insights from a human atrial model.

Despite the important role of electromechanical alternans in cardiac arrhythmogenesis, its molecular origin is not well understood. The appearance of calcium alternans has often been associated to fluctuations in the sarcoplasmic reticulum (SR) Ca loading. However, cytosolic calcium alternans observed without concurrent oscillations in the SR Ca content suggests an alternative mechanism related to a dysfunction in the dynamics of the ryanodine receptor (RyR2). We have investigated the effect of SR release refractoriness in the appearance of alternans, using a mathematical model of a single human atrial cell, based on the model by Nygren et al. (30), where we modified the dynamics of the RyR2 and of SR Ca release. The genesis of calcium alternans was studied stimulating the cell for different periods and values of the RyR2 recovery time from inactivation. At fast rates cytosolic calcium alternans were obtained without concurrent SR Ca content fluctuations. A transition from regular response to alternans was also observed, changing the recovery time from inactivation of the RyR2. This transition was found to be hysteretic, so for a given set of parameters different responses were observed. We then studied the relevance of RyR2 refractoriness for the generation of alternans, reproducing the same protocols as in recent experiments. In particular, restitution of Ca release during alternans was studied with a S1S2 protocol, obtaining a different response if the S2 stimulation was given after a long or a short release. We show that the experimental results can be explained by RyR2 refractoriness, arising from a slow RyR2 recovery from inactivation, stressing the role of the RyR2 in the genesis of alternans.

Quasicycles in a spatial predator-prey model.

We use spatial models of simple predator-prey interactions to predict that predator and prey numbers oscillate in time and space. These oscillations are not seen in the deterministic versions of the models, but are due to stochastic fluctuations about the time-independent solutions of the deterministic equations which are amplified due to the existence of a resonance. We calculate the power spectra of the fluctuations analytically and show that they agree well with results obtained from stochastic simulations. This work extends the analysis of these quasicycles from that previously developed for well-mixed systems to spatial systems, and shows that the ideas and methods used for nonspatial models naturally generalize to the spatial case.

The characteristics of species in an evolutionary food web model.

We explore the consequences of modifying the way in which species are defined in an evolutionary food web model. In the original version of the model, the species were defined in terms of a fixed number of features, chosen from a large number of possibilities. These features represented phenotypic and behavioural characteristics of the species. Speciation consisted in occasionally replacing one of the features by another. Here we modify this scheme by firstly allowing for a richer structure and secondly by testing whether we are able to eliminate the need for an explicit choice of features altogether. In the first case we allow for changing the number of features which define a species, as well as their nature, and find that in the resulting webs the higher trophic levels typically contain species with the greatest number of features. In the second case, by a simplification of the mechanisms for inter and intra-species competition, we construct a model without any explicit features and find that we are still able to grow model food webs. We assess the quality of the food webs produced and discuss the consequences of our findings for the future modelling of food webs.