Order statistics and heavy-tail distributions for planetary perturbations on Oort cloud comets

This paper tackles important aspects of comets dynamics from a statistical point of view. Existing methodology uses numerical integration for computing planetary perturbations for simulating such dynamics. This operation is highly computational. It is reasonable to wonder whenever statistical simulation of the perturbations can be much more easy to handle. The first step for answering such a question is to provide a statistical study of these perturbations in order to catch their main features. The statistical tools used are order statistics and heavy tail distributions. The study carried out indicated a general pattern exhibited by the perturbations around the orbits of the important planet. These characteristics were validated through statistical testing and a theoretical study based on Opik theory.Comment: 9 pages, 12 figures, submitted for publication in Astronomy and Astrophysic

A unified rheological model for cells and cellularised materials.

The mechanical response of single cells and tissues exhibits a broad distribution of time-scales that often gives rise to a distinctive power-law rheology. Such complex behaviour cannot be easily captured by traditional rheological approaches, making material characterisation and predictive modelling very challenging. Here, we present a novel model combining conventional viscoelastic elements with fractional calculus that successfully captures the macroscopic relaxation response of epithelial monolayers. The parameters extracted from the fitting of the relaxation modulus allow prediction of the response of the same material to slow stretch and creep, indicating that the model captured intrinsic material properties. Two characteristic times, derived from the model parameters, delimit different regimes in the materials response. We compared the response of tissues with the behaviour of single cells as well as intra and extra-cellular components, and linked the power-law behaviour of the epithelium to the dynamics of the cell cortex. Such a unified model for the mechanical response of biological materials provides a novel and robust mathematical approach to consistently analyse experimental data and uncover similarities and differences in reported behaviour across experimental methods and research groups. It also sets the foundations for more accurate computational models of tissue mechanics

The dynamic mechanical properties of cellularised aggregates.

Cellularised materials are composed of cells interfaced through specialised intercellular junctions that link the cytoskeleton of one cell to that of its neighbours allowing for transmission of forces. Cellularised materials are common in early development and adult tissues where they can be found in the form of cell sheets, cysts, or amorphous aggregates and in pathophysiological conditions such as cancerous tumours. Given the growing realisation that forces can regulate cell physiology and developmental processes, understanding how cellularised materials deform under mechanical stress or dissipate stress appear as key biological questions. In this review, we will discuss the dynamic mechanical properties of cellularised materials devoid of extracellular matrix

An integrative approach based on probabilistic modelling and statistical inference for morpho-statistical characterization of astronomical data

This paper describes several applications in astronomy and cosmology that are addressed using probabilistic modelling and statistical inference

Stress relaxation in epithelial monolayers is controlled by the actomyosin cortex

Epithelial monolayers are one-cell thick tissue sheets that separate internal and external environments. As part of their function, they have to withstand extrinsic mechanical stresses applied at high strain rates. However, little is known about how monolayers respond to mechanical deformations. Here, by subjecting suspended epithelial monolayers to stretch, we find that they dissipate stresses on a minute time-scale in a process that involves an increase in monolayer length, pointing to active remodelling of cell architecture during relaxation. Strikingly, monolayers consisting of tens of thousands of cells relax stress with similar dynamics to single rounded cells and both respond similarly to perturbations of actomyosin. By contrast, cell-cell junctional complexes and intermediate filaments do not relax tissue stress, but form stable connections between cells, allowing monolayers to behave rheologically as single cells. Taken together our data show that actomyosin dynamics governs the rheological properties of epithelial monolayers, dissipating applied stresses, and enabling changes in monolayer length.Peer ReviewedPostprint (published version

Tug-of-war between stretching and bending in living cell sheets

The balance between stretching and bending deformations characterizes shape transitions of thin elastic sheets. While stretching dominates the mechanical response in tension, bending dominates in compression after an abrupt buckling transition. Recently, experimental results in suspended living epithelial monolayers have shown that, due to the asymmetry in surface stresses generated by molecular motors across the thickness e of the epithelium, the free edges of such tissues spontaneously curl out-of-plane, stretching the sheet in-plane as a result. This suggests that a competition between bending and stretching sets the morphology of the tissue margin. In this paper, we use the framework of non-Euclidean plates to incorporate active pre-strain and spontaneous curvature to the theory of thin elastic shells. We show that, when the spontaneous curvature of the sheet scales like 1 / e , stretching and bending energies have the same scaling in the limit of a vanishingly small thickness and therefore both compete, in a way that is continuously altered by an external tension, to define the three-dimensional shape of the tissue

Actomyosin controls planarity and folding of epithelia in response to compression.

Throughout embryonic development and adult life, epithelia are subjected to compressive deformations. While these have been shown to trigger mechanosensitive responses such as cell extrusion and differentiation, which span tens of minutes, little is known about how epithelia adapt to compression over shorter timescales. Here, using suspended epithelia, we uncover the immediate response of epithelial tissues to the application of in-plane compressive strains (5-80%). We show that fast compression induces tissue buckling followed by actomyosin-dependent tissue flattening that erases the buckle within tens of seconds, in both mono- and multi-layered epithelia. Strikingly, we identify a well-defined limit to this response, so that stable folds form in the tissue when compressive strains exceed a 'buckling threshold' of ~35%. A combination of experiment and modelling shows that this behaviour is orchestrated by adaptation of the actomyosin cytoskeleton as it re-establishes tissue tension following compression. Thus, tissue pre-tension allows epithelia to both buffer against deformation and sets their ability to form and retain folds during morphogenesis.T.P.J.W. and N.K. were part of the EPSRC funded doctoral training programme CoMPLEX. J.F. and P.R. were funded by BBSRC grants (nos. BB/M003280 and BB/M002578) to G.T.C. and A.J.K. N.K. was funded by the Rosetrees Trust and the UCL Graduate School through a UCL Overseas Research Scholarship. A.L. was supported by an EMBO long-term post-doctoral fellowship. B.B. was supported by UCL, a BBSRC project grant (no. BB/K009001/1) and a CRUK programme grant (no. 17343). T.P.J.W., J.F., N.K., A.L. and G.T.C. were supported by a consolidator grant from the European Research Council to G.T.C. (MolCellTissMech, agreement no. 647186)

Simple blood fibrosis tests reduce unnecessary referrals for specialized evaluations of liver fibrosis in NAFLD and ALD patients

BACKGROUND: Liver fibrosis evaluation is mandatory in non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) to decide the patient management. Patients with these diseases are usually under the care of non-liver specialists who refer them to specialized centers where the most accurate fibrosis tests are available. We aimed to evaluate whether simple blood fibrosis tests available to all physicians help to reduce the rate of unnecessary referral of NAFLD and ALD patients without advanced fibrosis. METHODS: NAFLD and/or ALD patients newly referred to our center for a non-invasive evaluation of liver fibrosis were retrospectively included. The FibroMeter (FM, combination of blood markers and Fibroscan results) was defined as the reference test for specialized evaluation of liver fibrosis. A FM result <0.384 indicated the absence of advanced fibrosis and thus an "unnecessary referral". RESULTS: 558 patients were included (NAFLD: 283, ALD: 156, mixed NAFLD+ALD: 119). FM was <0.384 (unnecessary referral) in 58.8% of patients. FIB4 was <1.30 in 45.2% and eLIFT <8 in 47.7% of the patients. 84.9% of patients with FIB4 <1.30 and 85.3% of patients with eLIFT <8 had also FM <0.384. Therefore, using FIB4 or eLIFT as first-line evaluation of liver fibrosis decreased by three-fold the rate of unnecessary referral. The negative predictive value of FIB4 and eLIFT was >80% whatever the underlying cause of chronic liver disease. CONCLUSION: The use of eLIFT by non-liver specialists for NAFLD and ALD patients can improve the relevance of referrals for specialized evaluation of liver fibrosis

Where do long-period comets come from? 26 comets from the non-gravitational Oort spike

The apparent source region (or regions) of long-period comets as well as the definition of the dynamically new comet are still open questions.The aim of this investigation is to look for the apparent source of selected long period comets and to refine the definition of dynamically new comets. We show that incorporation of the non-gravitational forces into the orbit determination process significantly changes the situation. We determined precise non-gravitational orbits of all investigated comets and next followed numerically their past and future motion during one orbital period. Applying ingenious Sitarski's method of creating swarms of virtual comets compatible with observations, we were able to derive the uncertainties of original and future orbital elements, as well as the uncertainties of the previous and next perihelion distances. We concluded that the past and future evolution of cometary orbits under the Galactic tide perturbations is the only way to find which comets are really dynamically new. We also have shown that a significant percentage of long-period comets can visit the zone of visibility during at least two or three consecutive perihelion passages.Comment: Accepted for publication in MNRA

Liver Stiffness Measurement With FibroScan: Use the Right Probe in the Right Conditions!

INTRODUCTION: FibroScan\u27s M and XL probes give significantly different results, which could lead to misevaluation of liver fibrosis if the correct probe is not chosen. According to the manufacturer, the M probe should be used when the skin-liver capsule distance (SCD) is <25 mm, and the XL probe should be used when SCD is ≥25 mm. We aimed at validating this recommendation and defining the conditions of use for FibroScan probes in clinical practice. METHODS: Four hundred thirty-nine patients with biopsy-proven chronic liver disease were included. Of them, 382 had successful examinations with both M and XL probes. Advanced fibrosis was defined as Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) F ≥3 or Metavir F ≥2. RESULTS: In a same patient, XL probe results were significantly lower than M probe results: 7.9 (5.6-11.7) vs 9.5 (6.7-14.6) kPa, respectively (P < 0.001). After matching for age, sex, liver fibrosis, and serum transaminases, M probe results in patients with SCD <25 mm and XL probe results in those with SCD ≥25 mm did not significantly differ: 8.8 (6.0-12.0) vs 9.1 (6.7-12.8) kPa, respectively (P = 0.175). Of note, 81.4% of patients with body mass index (BMI) <32 kg/m had SCD <25 mm, and 77.7% of patients with BMI ≥32 kg/m had SCD ≥25 mm. A practical algorithm using BMI first and then the FibroScan Automatic Probe Selection tool was proposed to help physicians accurately choose which probe to use in clinical practice. CONCLUSIONS: There is no significant difference in results between M and XL probes when they are used in the right conditions. In clinical practice, the probe should be selected according to the BMI and the Automatic Probe Selection tool