Evolutionary dynamics of cancer cell populations under immune selection pressure and optimal control of chemotherapy

Increasing experimental evidence suggests that epigenetic and microenvironmental factors play a key role in cancer progression. In this respect, it is now generally recognized that the immune system can act as an additional selective pressure, which modulates tumor development and leads, through cancer immunoediting, to the selection for resistance to immune effector mechanisms. This may have serious implications for the design of effective anti-cancer protocols. Motivated by these considerations, we present a mathematical model for the dynamics of cancer and immune cells under the effects of chemotherapy and immunity-boosters. Tumor cells are modeled as a population structured by a continuous phenotypic trait, that is related to the level of resistance to receptor-induced cell death triggered by effector lymphocytes. The level of resistance can vary over time due to the effects of epigenetic modifications. In the asymptotic regime of small epimutations, we highlight the ability of the model to reproduce cancer immunoediting. In an optimal control framework, we tackle the problem of designing effective anti-cancer protocols. The results obtained suggest that chemotherapeutic drugs characterized by high cytotoxic effects can be useful for treating tumors of large size. On the other hand, less cytotoxic chemotherapy in combination with immunity-boosters can be effective against tumors of smaller size. Taken together, these results support the development of therapeutic protocols relying on combinations of less cytotoxic agents and immune-boosters to fight cancer in the early stages. © EDP Sciences, 2014

Technological Progress, Employment and the Lifetime of Capital

We study the impact of technological progress on the level of employment in a vintage capital model where: i) capital and labor are gross complementary; ii) labor supply is endogenous and indivisible; iii) there is full employment, and iv) the rate of labor-saving technological progress is endogenous. We characterize the stationary distributions of vintage capital goods and the corresponding equilibrium values for employment and capital lifetime. It is shown that both variables are non-monotonic functions of technological progress indicators. Technological accelerations are found to increase employment provided innovations are not too radical

Flashing annihilation term of a logistic kinetic as a mechanism leading to Pareto distributions

It is shown analytically that the flashing annihilation term of a Verhulst kinetic leads to the power--law distribution in the stationary state. For the frequency of switching slower than twice the free growth rate this provides the quasideterministic source of a Levy noises at the macroscopic level.Comment: 1 fi

Improving fleet solution – a case study

Transportation management is a logistical activity with a high impact on a company’s ability to compete in the market. Although the focus on cost reduction is the most usual concern with this activity, lead times and the quality of the service provided should also be considered depending on the market to be served. The goal of this research was to compare different fleet alternatives for a specific construction materials company and discuss which scenario is the most suited to fulfil the company’s customer service policy. A case study approach was developed, and four alternative scenarios were considered. These were compared both regarding the costs they involve, which was analysed using a vehicle routing problem heuristic, and the quality of the customer service they allow, which was assessed based on their ability to provide flexibility in the fleet occupancy rate to respond to unexpected orders. Evidence showed that the current fleet solution is not adequate and investment should be made only if the demand level increases, otherwise outsourcing should be considered along with a minimum level of the self-owned fleet.info:eu-repo/semantics/acceptedVersio

Molecular adaptation of a plant-bacterium outer membrane protease towards plague virulence factor Pla

<p>Abstract</p> <p>Background</p> <p>Omptins are a family of outer membrane proteases that have spread by horizontal gene transfer in Gram-negative bacteria that infect vertebrates or plants. Despite structural similarity, the molecular functions of omptins differ in a manner that reflects the life style of their host bacteria. To simulate the molecular adaptation of omptins, we applied site-specific mutagenesis to make Epo of the plant pathogenic <it>Erwinia pyrifoliae </it>exhibit virulence-associated functions of its close homolog, the plasminogen activator Pla of <it>Yersinia pestis</it>. We addressed three virulence-associated functions exhibited by Pla, i.e., proteolytic activation of plasminogen, proteolytic degradation of serine protease inhibitors, and invasion into human cells.</p> <p>Results</p> <p>Pla and Epo expressed in <it>Escherichia coli </it>are both functional endopeptidases and cleave human serine protease inhibitors, but Epo failed to activate plasminogen and to mediate invasion into a human endothelial-like cell line. Swapping of ten amino acid residues at two surface loops of Pla and Epo introduced plasminogen activation capacity in Epo and inactivated the function in Pla. We also compared the structure of Pla and the modeled structure of Epo to analyze the structural variations that could rationalize the different proteolytic activities. Epo-expressing bacteria managed to invade human cells only after all extramembranous residues that differ between Pla and Epo and the first transmembrane β-strand had been changed.</p> <p>Conclusions</p> <p>We describe molecular adaptation of a protease from an environmental setting towards a virulence factor detrimental for humans. Our results stress the evolvability of bacterial β-barrel surface structures and the environment as a source of progenitor virulence molecules of human pathogens.</p

From Linear to Nonlinear Utility in Vintage Capital Models

Optimization problems with nonlinear utility and endogenous capital lifetime are investigated in one- and two-sector modifications of the Solow vintage capital model. Both models have the same balanced growth path in the case of exponential technological change and labour. Turnpike theorems in normal form are proved for the optimal capital lifetime in both models. The differences between the cases of the linear and nonlinear utility are highlighted.balanced growth path, capital lifetime, nonlinear utility, optimization, turnpike theorems, vintage capital models,

Bifurcations in nonlinear integral models of biological systems

A bifurcation analysis is suggested for nonlinear integral models of age-distributed biological populations. The analysis shows that the integral model of one-species population with intra-species competition has zero and positive stationary states for some values of a bifurcation parameter. The nontrivial positive stationary state is initially stable and becomes unstable as the parameter grows. The obtained results are discussed and compared with the corresponding results in differential and difference models