MODELLING THE INFLUENCE OF NUCLEUS ELASTICITY ON CELL INVASION IN FIBER NETWORKS AND MICROCHANNELS

Cell migration in highly constrained extracellular matrices is exploited in scaffold-based tissue engineering and is fundamental in a wide variety of physiological and pathological phenomena, among others in cancer invasion and development. Research into the critical processes involved in cell migration has mainly focused on cell adhesion and proteolytic degradation of the external environment. However, rising evidence has recently shown that a number of cell-derived biophysical and mechanical parameters, among others nucleus stiffness and cell deformability, plays a major role in cell motility, especially in the ameboid-like migration mode in 3D confined tissue structures. We here present an extended cellular Potts model (CPM) first used to simulate a micro-fabricated migration chip, which tests the active invasive behavior of cancer cells into narrow channels. As distinct features of our approach, cells are modeled as compartmentalized discrete objects, differentiated in the nucleus and in the cytosolic region, while the migration chamber is composed of channels of different widths. We find that cell motile phenotype and velocity in open spaces (i.e., 2D flat surfaces or large channels) are not significantly influenced by cell elastic properties. On the contrary, the migratory behavior of cells within subcellular and subnuclear structures strongly relies on the deformability of the cytosol and of the nuclear cluster, respectively. Further, we characterize two migration dynamics: a stepwise way, characterized by fluctuations in cell length, within channels smaller than nucleus dimensions and a smooth sliding (i.e., maintaining constant cell length) behavior within channels larger than the nuclear cluster. These resulting observations are then extended looking at cell migration in an artificial fiber network, which mimics cell invasion in a 3D extracellular matrix. In particular, in this case, we analyze the effect of variations in elasticity of the nucleus on cell movement. In order to summarize, with our simulated migration assays, we demonstrate that the dimensionality of the environment strongly affects the migration phenotype and we suggest that the cytoskeletal and nuclear elastic characteristics correlate with the tumor cell's invasive potentia

National and international freight transport models: overview and ideas for further development

This paper contains a review of the literature on freight transport models, focussing on the types of models that have been developed since the nineties for forecasting, policy simulation and project evaluation at the national and international level. Models for production, attraction, distribution, modal split and assignment are discussed in the paper. Furthermore, the paper also includes a number of ideas for future development, especially for the regional and urban components within national freight transport models

Labour supply and taxes

In this paper we provide an overview of the literature relating labour supply to taxes and welfare benefits with a focus on presenting the empirical consensus. We begin with a basic continuous hours model, where individuals have completely free choice over their hours of work. We then consider fixed costs of work, the complications introduced by the benefits system, dynamic aspects of labour supply and we place the analysis in the context of the family. The key conclusion of this work is that in order to estimate the impact of tax reform and be able to generalise results, a structural approach that takes account of many of these issues is desirable. We then discuss the 'new Tax Responsiveness' literature which uses the response of taxable income to the marginal tax rate as a summary statistic of the behavioural response to taxation. Underlying this approach is the unsatisfactory nature of using hours as a proxy for labour effort for those with high levels of autonomy on the job and who already work long hours, such as the self employed or senior executives. After discussing relevant theory we then provide a summary of empirical estimates and the methodology underlying the studies. Our conclusion is that hours of work are relatively inelastic for men, but are a little more responsive for married women and lone mothers. On the other hand, participation is quite sensitive to taxation and benefits for women. Within this paper we present new estimates form a discrete participation model for both married and single men based on the numerous reforms over the past two decades in the UK. We find that the participation of low education men is somewhat more responsive to incentives than previously thought. For men with high levels of education, participation is virtually unresponsive; here the literature on taxable income suggests that there may be significant welfare costs of taxation, although much of this seems to be a result of shifting income and consumption to non-taxable forms as opposed to actual reductions in work effort

Seismic response trends evaluation and finite element model calibration of an instrumented RC building considering soil-structure interaction and non-structural components

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Modelling the Dynamics of a Public Health Care System: Evidence from Time-Series Data

The English National Health Service was established in 1948, and has therefore yielded some long time series data on health system performance. Waiting times for inpatient care have been a persistent cause of policy concern since the creation of the NHS. This paper develops a theoretical model of the dynamic interaction between key indicators of health system performance. It then investigates empirically the relationship between hospital activity, waiting times and population characteristics using aggregate time-series data for the NHS over the period 1952-2005. Structural Vector Auto-Regression suggests that in the long run: a) higher activity is associated with lower waiting times (elasticity = -0.9%); b) a higher proportion of old population is associated with higher waiting times (elasticity = 1.6%). In the short run, higher lagged waiting time leads to higher activity (elasticity = 0.2%). We also find that shocks in waiting times are countered by higher activity, so the effect is only temporary, while shocks in activity have a permanent effect. We conclude that policies to reduce waiting times should focus on initiatives that increase hospital activity.Waiting times, Dynamics, Vector Auto-Regression.

On the critical nature of plastic flow: one and two dimensional models

Steady state plastic flows have been compared to developed turbulence because the two phenomena share the inherent complexity of particle trajectories, the scale free spatial patterns and the power law statistics of fluctuations. The origin of the apparently chaotic and at the same time highly correlated microscopic response in plasticity remains hidden behind conventional engineering models which are based on smooth fitting functions. To regain access to fluctuations, we study in this paper a minimal mesoscopic model whose goal is to elucidate the origin of scale free behavior in plasticity. We limit our description to fcc type crystals and leave out both temperature and rate effects. We provide simple illustrations of the fact that complexity in rate independent athermal plastic flows is due to marginal stability of the underlying elastic system. Our conclusions are based on a reduction of an over-damped visco-elasticity problem for a system with a rugged elastic energy landscape to an integer valued automaton. We start with an overdamped one dimensional model and show that it reproduces the main macroscopic phenomenology of rate independent plastic behavior but falls short of generating self similar structure of fluctuations. We then provide evidence that a two dimensional model is already adequate for describing power law statistics of avalanches and fractal character of dislocation patterning. In addition to capturing experimentally measured critical exponents, the proposed minimal model shows finite size scaling collapse and generates realistic shape functions in the scaling laws.Comment: 72 pages, 40 Figures, International Journal of Engineering Science for the special issue in honor of Victor Berdichevsky, 201

Financial Disintermediation in the 1990s : Implications on Monetary Policy in Malaysia

The increased financial disintermediation that characterizes the Malaysia's financial system since the early 1990s has contributed towards changes in the dynamics of monetary transmission mechanism. Using quarterly data from 1980: 1 to 2005: 4, we found a greater effectiveness of monetary policy during the pre-1990:3 period, but the post-1990:3 period poses much difficulty for the conduct of monetary policy. Innovations in the financial market appeared to have led to lower output variability. Further, when the real interest rate is made a function of financial disintermediation, the real interest rate appeared to have lost its significance in influencing real variables in the post-1990: 3 period. This study did not, however, find evidence in support of the significance of the real interest rate in affecting real variables through the direct financing channel via the capital market.bank lending channel, capital market, cointegration, VAR

Endogenous Fishing Mortalities: a State-Space Bioeconomic Model

A methodology that endogenously determines catchability functions that link fi shing mortality with contemporaneous stock abundance is presented. We consider a stochastic age-structured model for a fishery composed by a number of fi shing units (fleets, vessels or métiers) that optimally select the level of fishing effort to be applied considering total mortalities as given. The introduction of a balance constrain which guarantees that total mortality is equal to the sum of individual fi shing mortalities optimally selected, enables total fishing mortality to be determined as a combination of contemporaneous abundance and stochastic processes affecting the fishery. In this way, future abundance can be projected as a dynamic system that depends on contemporaneous abundance. The model is generic and can be applied to several issues of fisheries management. In particular, we illustrate how to apply the methodology to assess the floating band target management regime for controlling fishing mortalities which is inspired in the new multi-annual plans. Our results support this management regime for the Mediterranean demersal fishery in Northern Spain.This work was funded by the European Commission as part of the MINOUW project (H2020-SFS-2014-2, number 634495) and the Spanish Ministry of Economy, Industry and Competitiveness (ECO2016-78819-R, AEI/FEDER, UE

Modelling Hen Harrier Dynamics to Inform Human-Wildlife Conflict Resolution : A Spatially-Realistic, Individual-Based Approach

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