ELECANS--an integrated model development environment for multiscale cancer systems biology.

MOTIVATION: Computational multiscale models help cancer biologists to study the spatiotemporal dynamics of complex biological systems and to reveal the underlying mechanism of emergent properties. RESULTS: To facilitate the construction of such models, we have developed a next generation modelling platform for cancer systems biology, termed 'ELECANS' (electronic cancer system). It is equipped with a graphical user interface-based development environment for multiscale modelling along with a software development kit such that hierarchically complex biological systems can be conveniently modelled and simulated by using the graphical user interface/software development kit combination. Associated software accessories can also help users to perform post-processing of the simulation data for visualization and further analysis. In summary, ELECANS is a new modelling platform for cancer systems biology and provides a convenient and flexible modelling and simulation environment that is particularly useful for those without an intensive programming background. AVAILABILITY AND IMPLEMENTATION: ELECANS, its associated software accessories, demo examples, documentation and issues database are freely available at http://sbie.kaist.ac.kr/sub_0204.php. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Wideband antireflective circular polarizer exhibiting a perfect dark state in organic light-emitting-diode display.

We proposed wideband antireflective circular polarizer for realizing a true black state in all viewing directions in organic light-emitting-diode displays (OLEDs). Present commercialized wideband circular polarizer consisted of a half wave and a quarter wave plates having the refractive index parameter (Nz) of 1.5 in both films exhibits light leakage in the oblique viewing directions, deteriorating image quality of a black state. We evaluated Nzs of both films and proposed a new wideband antireflective circular polarizer with a perfect dark state in all viewing directions with Nz = 0.5 in both plates, which will greatly improve image quality of OLEDs.

Toward Community Standards and Software for Whole-Cell Modeling.

OBJECTIVE: Whole-cell (WC) modeling is a promising tool for biological research, bioengineering, and medicine. However, substantial work remains to create accurate comprehensive models of complex cells. METHODS: We organized the 2015 Whole-Cell Modeling Summer School to teach WC modeling and evaluate the need for new WC modeling standards and software by recoding a recently published WC model in the Systems Biology Markup Language. RESULTS: Our analysis revealed several challenges to representing WC models using the current standards. CONCLUSION: We, therefore, propose several new WC modeling standards, software, and databases. SIGNIFICANCE: We anticipate that these new standards and software will enable more comprehensive models.

Network-based identification of feedback modules that control RhoA activity and cell migration.

Cancer cell migration enables metastatic spread causing most cancer deaths. Rho-family GTPases control cell migration, but being embedded in a highly interconnected feedback network, the control of their dynamical behavior during cell migration remains elusive. To address this question, we reconstructed the Rho-family GTPases signaling network involved in cell migration, and developed a Boolean network model to analyze the different states and emergent rewiring of the Rho-family GTPases signaling network at protrusions and during extracellular matrix-dependent cell migration. Extensive simulations and experimental validations revealed that the bursts of RhoA activity induced at protrusions by EGF are regulated by a negative-feedback module composed of Src, FAK, and CSK. Interestingly, perturbing this module interfered with cyclic Rho activation and extracellular matrix-dependent migration, suggesting that CSK inhibition can be a novel and effective intervention strategy for blocking extracellular matrix-dependent cancer cell migration, while Src inhibition might fail, depending on the genetic background of cells. Thus, this study provides new insights into the mechanisms that regulate the intricate activation states of Rho-family GTPases during extracellular matrix-dependent migration, revealing potential new targets for interfering with extracellular matrix-dependent cancer cell migration.

The APC network regulates the removal of mutated cells from colonic crypts.

Self-renewal is essential for multicellular organisms but carries the risk of somatic mutations that can lead to cancer, which is particularly critical for rapidly renewing tissues in a highly mutagenic environment such as the intestinal epithelium. Using computational modeling and in vivo experimentation, we have analyzed how adenomatous polyposis coli (APC) mutations and ß-catenin aberrations affect the maintenance of mutant cells in colonic crypts. The increasing abundance of APC along the crypt axis forms a gradient of cellular adhesion that causes more proliferative cells to accelerate their movement toward the top of the crypt, where they are shed into the lumen. Thus, the normal crypt can efficiently eliminate ß-catenin mutant cells, whereas APC mutations favor retention. Together, the molecular design of the APC/ß-catenin signaling network integrates cell proliferation and migration dynamics to translate intracellular signal processing and protein gradients along the crypt into intercellular interactions and whole-crypt physiological or pathological behavior.