184 research outputs found

    Mutation Size Optimizes Speciation in an Evolutionary Model

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    The role of mutation rate in optimizing key features of evolutionary dynamics has recently been investigated in various computational models. Here, we address the related question of how maximum mutation size affects the formation of species in a simple computational evolutionary model. We find that the number of species is maximized for intermediate values of a mutation size parameter μ; the result is observed for evolving organisms on a randomly changing landscape as well as in a version of the model where negative feedback exists between the local population size and the fitness provided by the landscape. The same result is observed for various distributions of mutation values within the limits set by μ. When organisms with various values of μ compete against each other, those with intermediate μ values are found to survive. The surviving values of μ from these competition simulations, however, do not necessarily coincide with the values that maximize the number of species. These results suggest that various complex factors are involved in determining optimal mutation parameters for any population, and may also suggest approaches for building a computational bridge between the (micro) dynamics of mutations at the level of individual organisms and (macro) evolutionary dynamics at the species level

    Quasi-Neutral theory of epidemic outbreaks

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    Some epidemics have been empirically observed to exhibit outbreaks of all possible sizes, i.e., to be scalefree or scale-invariant. Different explanations for this finding have been put forward; among them there is a model for "accidental pathogens" which leads to power-law distributed outbreaks without apparent need of parameter fine tuning. This model has been claimed to be related to self-organized criticality, and its critical properties have been conjectured to be related to directed percolation. Instead, we show that this is a (quasi) neutral model, analogous to those used in Population Genetics and Ecology, with the same critical behavior as the voter-model, i.e. the theory of accidental pathogens is a (quasi)-neutral theory. This analogy allows us to explain all the system phenomenology, including generic scale invariance and the associated scaling exponents, in a parsimonious and simple way.Comment: 13 pages, 6 figures Accepted for publication in PLoS ONE the text have been modified in orden to improve the figure's resolutio

    Model for in vivo progression of tumors based on co-evolving cell population and vasculature

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    With countless biological details emerging from cancer experiments, there is a growing need for minimal mathematical models which simultaneously advance our understanding of single tumors and metastasis, provide patient-personalized predictions, whilst avoiding excessive hard-to-measure input parameters which complicate simulation, analysis and interpretation. Here we present a model built around a co-evolving resource network and cell population, yielding good agreement with primary tumors in a murine mammary cell line EMT6-HER2 model in BALB/c mice and with clinical metastasis data. Seeding data about the tumor and its vasculature from in vivo images, our model predicts corridors of future tumor growth behavior and intervention response. A scaling relation enables the estimation of a tumor's most likely evolution and pinpoints specific target sites to control growth. Our findings suggest that the clinically separate phenomena of individual tumor growth and metastasis can be viewed as mathematical copies of each other differentiated only by network structure

    Activation of PPARγ in Myeloid Cells Promotes Lung Cancer Progression and Metastasis

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    Activation of peroxisome proliferator-activated receptor-γ (PPARγ) inhibits growth of cancer cells including non-small cell lung cancer (NSCLC). Clinically, use of thiazolidinediones, which are pharmacological activators of PPARγ is associated with a lower risk of developing lung cancer. However, the role of this pathway in lung cancer metastasis has not been examined well. The systemic effect of pioglitazone was examined in two models of lung cancer metastasis in immune-competent mice. In an orthotopic model, murine lung cancer cells implanted into the lungs of syngeneic mice metastasized to the liver and brain. As a second model, cancer cells injected subcutaneously metastasized to the lung. In both models systemic administration of pioglitazone increased the rate of metastasis. Examination of tissues from the orthotopic model demonstrated increased numbers of arginase I-positive macrophages in tumors from pioglitazone-treated animals. In co-culture experiments of cancer cells with bone marrow-derived macrophages, pioglitazone promoted arginase I expression in macrophages and this was dependent on the expression of PPARγ in the macrophages. To assess the contribution of PPARγ in macrophages to cancer progression, experiments were performed in bone marrow-transplanted animals receiving bone marrow from Lys-M-Cre+/PPARγflox/flox mice, in which PPARγ is deleted specifically in myeloid cells (PPARγ-Macneg), or control PPARγflox/flox mice. In both models, mice receiving PPARγ-Macneg bone marrow had a marked decrease in secondary tumors which was not significantly altered by treatment with pioglitazone. This was associated with decreased numbers of arginase I-positive cells in the lung. These data support a model in which activation of PPARγ may have opposing effects on tumor progression, with anti-tumorigenic effects on cancer cells, but pro-tumorigenic effects on cells of the microenvironment, specifically myeloid cells

    Quantifying and predicting success in show business

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    Recent studies in the science of success have shown that the highest-impact works of scientists or artists happen randomly and uniformly over the individual's career. Yet in certain artistic endeavours, such as acting in films and TV, having a job is perhaps the most important achievement: success is simply making a living. By analysing a large online database of information related to films and television we are able to study the success of those working in the entertainment industry. We first support our initial claim, finding that two in three actors are "one-hit wonders". In addition we find that, in agreement with previous works, activity is clustered in hot streaks, and the percentage of careers where individuals are active is unpredictable. However, we also discover that productivity in show business has a range of distinctive features, which are predictable. We unveil the presence of a rich-get-richer mechanism underlying the assignment of jobs, with a Zipf law emerging for total productivity. We find that productivity tends to be highest at the beginning of a career and that the location of the "annus mirabilis" -- the most productive year of an actor -- can indeed be predicted. Based on these stylized signatures we then develop a machine learning method which predicts, with up to 85% accuracy, whether the annus mirabilis of an actor has yet passed or if better days are still to come. Finally, our analysis is performed on both actors and actresses separately, and we reveal measurable and statistically significant differences between these two groups across different metrics, thereby providing compelling evidence of gender bias in show business.Comment: 6 Figure

    Status and Prospects of ZnO-Based Resistive Switching Memory Devices

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    In the advancement of the semiconductor device technology, ZnO could be a prospective alternative than the other metal oxides for its versatility and huge applications in different aspects. In this review, a thorough overview on ZnO for the application of resistive switching memory (RRAM) devices has been conducted. Various efforts that have been made to investigate and modulate the switching characteristics of ZnO-based switching memory devices are discussed. The use of ZnO layer in different structure, the different types of filament formation, and the different types of switching including complementary switching are reported. By considering the huge interest of transparent devices, this review gives the concrete overview of the present status and prospects of transparent RRAM devices based on ZnO. ZnO-based RRAM can be used for flexible memory devices, which is also covered here. Another challenge in ZnO-based RRAM is that the realization of ultra-thin and low power devices. Nevertheless, ZnO not only offers decent memory properties but also has a unique potential to be used as multifunctional nonvolatile memory devices. The impact of electrode materials, metal doping, stack structures, transparency, and flexibility on resistive switching properties and switching parameters of ZnO-based resistive switching memory devices are briefly compared. This review also covers the different nanostructured-based emerging resistive switching memory devices for low power scalable devices. It may give a valuable insight on developing ZnO-based RRAM and also should encourage researchers to overcome the challenges

    Brain energy rescue:an emerging therapeutic concept for neurodegenerative disorders of ageing

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    The brain requires a continuous supply of energy in the form of ATP, most of which is produced from glucose by oxidative phosphorylation in mitochondria, complemented by aerobic glycolysis in the cytoplasm. When glucose levels are limited, ketone bodies generated in the liver and lactate derived from exercising skeletal muscle can also become important energy substrates for the brain. In neurodegenerative disorders of ageing, brain glucose metabolism deteriorates in a progressive, region-specific and disease-specific manner — a problem that is best characterized in Alzheimer disease, where it begins presymptomatically. This Review discusses the status and prospects of therapeutic strategies for countering neurodegenerative disorders of ageing by improving, preserving or rescuing brain energetics. The approaches described include restoring oxidative phosphorylation and glycolysis, increasing insulin sensitivity, correcting mitochondrial dysfunction, ketone-based interventions, acting via hormones that modulate cerebral energetics, RNA therapeutics and complementary multimodal lifestyle changes
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