Cancer growth and metastasis as a metaphor of Go gaming: An Ising model approach

© 2018 Barradas-Bautista et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestric ted use, distribution, and reproduction in any medium, provided the original author and source are credited. This work aims for modeling and simulating the metastasis of cancer, via the analogy between the cancer process and the board game Go. In the game of Go, black stones that play first could correspond to a metaphor of the birth, growth, and metastasis of cancer. Moreover, playing white stones on the second turn could correspond the inhibition of cancer invasion. Mathematical modeling and algorithmic simulation of Go may therefore benefit the efforts to deploy therapies to surpass cancer illness by providing insight into the cellular growth and expansion over a tissue area. We use the Ising Hamiltonian, that models the energy exchange in interacting particles, for modeling the cancer dynamics. Parameters in the energy function refer the biochemical elements that induce cancer birth, growth, and metastasis; as well as the biochemical immune system process of defense

Urban-Tissue Optimization through Evolutionary Computation

The experiments analyzed in this paper focus their research on the use of Evolutionary Computation (EC) applied to a parametrized urban tissue. Through the application of EC, it is possible to develop a design under a single model that addresses multiple conflicting objectives. The experiments presented are based on Cerdà’s master plan in Barcelona, specifically on the iconic Eixample block which is grouped into a 4 × 4 urban Superblock. The proposal aims to reach the existing high density of the city while reclaiming the block relations proposed by Cerdà’s original plan. Generating and ranking multiple individuals in a population through several generations ensures a flexible solution rather than a single “optimal” one. Final results in the Pareto front show a successful and diverse set of solutions that approximate Cerdà’s and the existing Barcelona’s Eixample states. Further analysis proposes different methodologies and considerations to choose appropriate individuals within the front depending on design requirements

Modeling the Searching Behavior of Social Monkeys

We discuss various features of the trajectories of spider monkeys looking for food in a tropical forest, as observed recently in an extensive {\it in situ} study. Some of the features observed can be interpreted as the result of social interactions. In addition, a simple model of deterministic walk in a random environment reproduces the observed angular correlations between successive steps, and in some cases, the emergence of L\'evy distributions for the length of the steps.Comment: 7 pages, 3 figure

Bifurcating spatially heterogeneous solutions in a chemotaxis model for biological pattern formation

We consider a simple cell-chemotaxis model for spatial pattern formation on two-dimensional domains proposed by Oster and Murray (1989,J. exp. Zool. 251, 186–202). We determine finite-amplitude, steady-state, spatially heterogeneous solutions and study the effect of domain growth on the resulting patterns. We also investigate in-depth bifurcating solutions as the chemotactic parameter varies. This numerical study shows that this deceptively simple-chemotaxis model can produce a surprisingly rich spectrum of complex spatial patterns

Assessment of a targeted resequencing assay as a support tool in the diagnosis of lysosomal storage disorders

BACKGROUND: With over 50 different disorders and a combined incidence of up to 1/3000 births, lysosomal storage diseases (LSDs) constitute a major public health problem and place an enormous burden on affected individuals and their families. Many factors make LSD diagnosis difficult, including phenotype and penetrance variability, shared signs and symptoms, and problems inherent to biochemical diagnosis. Developing a powerful diagnostic tool could mitigate the protracted diagnostic process for these families, lead to better outcomes for current and proposed therapies, and provide the basis for more appropriate genetic counseling. METHODS: We have designed a targeted resequencing assay for the simultaneous testing of 57 lysosomal genes, using in-solution capture as the enrichment method and two different sequencing platforms. A total of 84 patients with high to moderate-or low suspicion index for LSD were enrolled in different centers in Spain and Portugal, including 18 positive controls. RESULTS: We correctly diagnosed 18 positive blinded controls, provided genetic diagnosis to 25 potential LSD patients, and ended with 18 diagnostic odysseys. CONCLUSION: We report the assessment of a next-generation-sequencing-based approach as an accessory tool in the diagnosis of LSDs, a group of disorders which have overlapping clinical profiles and genetic heterogeneity. We have also identified and quantified the strengths and limitations of next generation sequencing (NGS) technology applied to diagnosis

Phase transitions in tumor growth VI: Epithelial–Mesenchymal transition

Herewith we discuss a network model of the epithelial–mesenchymal transition (EMT) based on our previous proposed framework. The EMT appears as a “first order” phase transition process, analogous to the transitions observed in the chemical–physical field. Chiefly, EMT should be considered a transition characterized by a supercritical Andronov–Hopf bifurcation, with the emergence of limit cycle and, consequently, a cascade of saddle-foci Shilnikov's bifurcations. We eventually show that the entropy production rate is an EMT-dependent function and, as such, its formalism reminds the van der Waals equation.Fil: Guerra, A.. Universidad de La Habana; CubaFil: Rodriguez, D. J.. Universidad de La Habana; CubaFil: Montero, S.. Medical Sciences University Of Havana; CubaFil: Betancourt Mar, J. A.. Universidad de La Habana; CubaFil: Martín Pardo, Reinaldo Román. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; Argentina. Mexican Institute Of Complex Systems. Tamaulipas; MéxicoFil: Silva Lamar, Eduardo. Universidad de La Habana; CubaFil: Bizzarri, María Julia. Universidad de La Habana; CubaFil: Cocho, G.. Universidad Nacional Autónoma de México; MéxicoFil: Mansilla, R.. Universidad Nacional Autónoma de México; MéxicoFil: Nieto Villar, José Manuel. Universidad de La Habana; Cub

Newborn screening for medium-chain acyl-CoA dehydrogenase deficiency: regional experience and high incidence of carnitine deficiency

Background Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the most common inherited defect in the mitochondrial fatty acid oxidation pathway, resulting in significant morbidity and mortality in undiagnosed patients. Newborn screening (NBS) has considerably improved MCADD outcome, but the risk of complication remains in some patients. The aim of this study was to evaluate the relationship between genotype, biochemical parameters and clinical data at diagnosis and during follow-up, in order to optimize monitoring of these patients. Methods We carried out a multicenter study in southwest Europe, of MCADD patients detected by NBS. Evaluated NBS data included free carnitine (C0) and the acylcarnitines C8, C10, C10:1 together with C8/C2 and C8/C10 ratios, clinical presentation parameters and genotype, in 45 patients. Follow-up data included C0 levels, duration of carnitine supplementation and occurrence of metabolic crises. Results C8/C2 ratio and C8 were the most accurate biomarkers of MCADD in NBS. We found a high number of patients homozygous for the prevalent c.985A > G mutation (75%). Moreover, in these patients C8, C8/C10 and C8/C2 were higher than in patients with other genotypes, while median value of C0 was significantly lower (23 μmol/L vs 36 μmol/L). The average follow-up period was 43 months. To keep carnitine levels within the normal range, carnitine supplementation was required in 82% of patients, and for a longer period in patients homozygotes for the c.985A>G mutation than in patients with other genotypes (average 31 vs 18 months). Even with treatment, median C0 levels remained lower in homozygous patients than in those with other genotypes (14 μmol/L vs 22 μmol/L). Two patients died and another three suffered a metabolic crisis, all of whom were homozygous for the c.985 A>G mutation. Conclusions Our data show a direct association between homozygosity for c.985A>G and lower carnitine values at diagnosis, and a higher dose of carnitine supplementation for maintenance within the normal range. This study contributes to a better understanding of the relationship between genotype and phenotype in newborn patients with MCADD detected through screening which could be useful in improving follow-up strategies and clinical outcome

First passage and arrival time densities for L\'evy flights and the failure of the method of images

We discuss the first passage time problem in the semi-infinite interval, for homogeneous stochastic Markov processes with L{\'e}vy stable jump length distributions $\lambda(x)\sim\ell^{\alpha}/|x|^{1+\alpha}$ ($|x|\gg\ell$), namely, L{\'e}vy flights (LFs). In particular, we demonstrate that the method of images leads to a result, which violates a theorem due to Sparre Andersen, according to which an arbitrary continuous and symmetric jump length distribution produces a first passage time density (FPTD) governed by the universal long-time decay $\sim t^{-3/2}$. Conversely, we show that for LFs the direct definition known from Gaussian processes in fact defines the probability density of first arrival, which for LFs differs from the FPTD. Our findings are corroborated by numerical results.Comment: 8 pages, 3 figures, iopart.cls style, accepted to J. Phys. A (Lett

Abundance of unknots in various models of polymer loops

A veritable zoo of different knots is seen in the ensemble of looped polymer chains, whether created computationally or observed in vitro. At short loop lengths, the spectrum of knots is dominated by the trivial knot (unknot). The fractional abundance of this topological state in the ensemble of all conformations of the loop of $N$ segments follows a decaying exponential form, $\sim \exp (-N/N_0)$, where $N_0$ marks the crossover from a mostly unknotted (ie topologically simple) to a mostly knotted (ie topologically complex) ensemble. In the present work we use computational simulation to look closer into the variation of $N_0$ for a variety of polymer models. Among models examined, $N_0$ is smallest (about 240) for the model with all segments of the same length, it is somewhat larger (305) for Gaussian distributed segments, and can be very large (up to many thousands) when the segment length distribution has a fat power law tail.Comment: 13 pages, 6 color figure

Tear fluid biomarkers in ocular and systemic disease: potential use for predictive, preventive and personalised medicine

In the field of predictive, preventive and personalised medicine, researchers are keen to identify novel and reliable ways to predict and diagnose disease, as well as to monitor patient response to therapeutic agents. In the last decade alone, the sensitivity of profiling technologies has undergone huge improvements in detection sensitivity, thus allowing quantification of minute samples, for example body fluids that were previously difficult to assay. As a consequence, there has been a huge increase in tear fluid investigation, predominantly in the field of ocular surface disease. As tears are a more accessible and less complex body fluid (than serum or plasma) and sampling is much less invasive, research is starting to focus on how disease processes affect the proteomic, lipidomic and metabolomic composition of the tear film. By determining compositional changes to tear profiles, crucial pathways in disease progression may be identified, allowing for more predictive and personalised therapy of the individual. This article will provide an overview of the various putative tear fluid biomarkers that have been identified to date, ranging from ocular surface disease and retinopathies to cancer and multiple sclerosis. Putative tear fluid biomarkers of ocular disorders, as well as the more recent field of systemic disease biomarkers, will be shown