Simulating Brain Tumor Heterogeneity with a Multiscale Agent-Based Model: Linking Molecular Signatures, Phenotypes and Expansion Rate

We have extended our previously developed 3D multi-scale agent-based brain tumor model to simulate cancer heterogeneity and to analyze its impact across the scales of interest. While our algorithm continues to employ an epidermal growth factor receptor (EGFR) gene-protein interaction network to determine the cells' phenotype, it now adds an explicit treatment of tumor cell adhesion related to the model's biochemical microenvironment. We simulate a simplified tumor progression pathway that leads to the emergence of five distinct glioma cell clones with different EGFR density and cell 'search precisions'. The in silico results show that microscopic tumor heterogeneity can impact the tumor system's multicellular growth patterns. Our findings further confirm that EGFR density results in the more aggressive clonal populations switching earlier from proliferation-dominated to a more migratory phenotype. Moreover, analyzing the dynamic molecular profile that triggers the phenotypic switch between proliferation and migration, our in silico oncogenomics data display spatial and temporal diversity in documenting the regional impact of tumorigenesis, and thus support the added value of multi-site and repeated assessments in vitro and in vivo. Potential implications from this in silico work for experimental and computational studies are discussed.Comment: 37 pages, 10 figure

How Network Externalities Can Exacerbate Intergroup Inequality

The authors describe a common but largely unrecognized mechanism that produces and exacerbates intergroup inequality: the diffusion of valuable practices with positive network externalities through social networks whose members differentially possess characteristics associated with adoption. The authors examine two cases: the first, to explore the mechanism's implications and, the second, to demonstrate its utility in analyzing empirical data. In the first, the diffusion of Internet use, network effects increase adoption's benefits to associates of prior adopters. An agent-based model demonstrates positive, monotonic relationships, given externalities, between homophily bias and intergroup inequality in equilibrium adoption rates. In the second, rural-urban migration in Thailand, network effects reduce risk to persons whose networks include prior migrants. Analysis of longitudinal individual-level migration data indicates that network homophily interacts with network externalities to induce divergence of migration rates among otherwise similar villages.Sociolog

Analyzing the determinants of financial distress in Indonesian mining companies

Purpose: The objective of the study is to analyze the effect of leverage, liquidity and managerial ownership on financial distress at mining companies in Indonesia. The study also examines the moderating role of profitability on the effects of leverage, liquidity and managerial ownership on financial distress. Design/Methodology/Approach: The population of this study is 41 mining sector companies listed in Indonesian Stock Exchange in 2013-2015. There are 17 companies as the sample of the study taken by purposive sampling method; then there are 51 units of analysis which are suitable to the predetermined criteria. Data are analyzed by descriptive statistical analysis and logistic regression for inferential conclusions. Findings: The results of the study show that the leverage has a positive effect on financial distress. Then, liquidity and managerial ownership do not have any effect on financial distress. Furthermore, profitability as the moderating variable is not proven to moderate the effect of leverage and managerial ownership on financial distress. However, profitability is proven to moderate significantly the effect of liquidity on financial distress. Practical Implications: This study has the guidance and or feedback to the company management to avoid financial distress. Originality/Value: The research places profitability as the moderating variable to analyze the simultaneous effect among leverage, liquidity, managerial ownership with profitability on financial distress. Then, it takes the mining sector companies as the sample to be analysed.peer-reviewe

Is Poker a Skill Game? New Insights from Statistical Physics

During last years poker has gained a lot of prestige in several countries and, beyond to be one of the most famous card games, it represents a modern challenge for scientists belonging to different communities, spanning from artificial intelligence to physics and from psychology to mathematics. Unlike games like chess, the task of classifying the nature of poker (i.e., as 'skill game' or gambling) seems really hard and it also constitutes a current problem, whose solution has several implications. In general, gambling offers equal winning probabilities both to rational players (i.e., those that use a strategy) and to irrational ones (i.e., those without a strategy). Therefore, in order to uncover the nature of poker, a viable way is comparing performances of rational versus irrational players during a series of challenges. Recently, a work on this topic revealed that rationality is a fundamental ingredient to succeed in poker tournaments. In this study we analyze a simple model of poker challenges by a statistical physics approach, with the aim to uncover the nature of this game. As main result we found that, under particular conditions, few irrational players can turn poker into gambling. Therefore, although rationality is a key ingredient to succeed in poker, also the format of challenges has an important role in these dynamics, as it can strongly influence the underlying nature of the game. The importance of our results lies on related implications, as for instance in identifying the limits poker can be considered as a `skill game' and, as a consequence, which kind of format must be chosen to devise algorithms able to face humans.Comment: 12 pages, 4 figure

Simulation Models for Analyzing the Dynamic Costs of Process-aware Information Systems

Introducing process-aware information systems (PAIS) in enterprises (e.g., workflow management systems, case handling systems) is associated with high costs. Though cost estimation has received considerable attention in software engineering for many years, it is difficult to apply existing approaches to PAIS. This difficulty particularly stems from the inability of existing estimation techniques to deal with the complex interplay of the many technological, organizational and project-driven factors which emerge in the context of PAIS. In response to this problem, this paper proposes an approach which utilizes simulation models for investigating the dynamic costs of PAIS engineering projects. We motivate the need for simulation, discuss the development and execution of simulation models, and give an illustrating example. The present work has been accomplished in the EcoPOST project, which deals with the development of a comprehensive evaluation framework for analyzing PAIS engineering projects from a value-based perspective

On the investment implications of bankruptcy laws

Axiomatic analysis of bankruptcy problems reveals three major principles: (i) proportionality (PRO), (ii) equal awards (EA), and (iii) equal losses (EL). However, most real life bankruptcy procedures implement only the proportionality principle. We construct a noncooperative investment game to explore whether the explanation lies in the alternative implications of these principles on investment behavior. Our results are as follows (i) EL always induces higher total investment than PRO which in turn induces higher total investment than EA; (ii) PRO always induces higher egalitarian social welfare than both EA and EL in interior equilibria; (iii) PRO induces higher utilitarian social welfare than EL in interior equilibria but its relation to EA depends on the parameter values (however, a numerical analysis shows that on a large part of the parameter space, PRO induces higher utilitarian social welfare than EA)