Gaining Insights into Conceptual Models: A Graph-Theoretic Querying Approach

Modern complex systems include products and services that comprise many interconnected pieces of integrated hardware and software, which are expected to serve humans interacting with them. As technology advances, expectations of a smooth, flawless system operation grow. Model-based systems engineering, an approach based on conceptual models, copes with this challenge. Models help construct formal system representations, visualize them, understand the design, simulate the system, and discover design flaws early on. Modeling tools can benefit tremendously from querying capabilities that enable gaining deep insights into system aspects that direct model observations do not reveal. Querying mechanisms can unveil and explain cause-and-effect phenomena, identify central components, and estimate impacts or risks associated with changes. Being connected networks of system elements, models can be effectively represented as graphs, to which queries are applied. Capitalizing on established graph-theoretic algorithms to solve a large variety of problems can elevate the modeling experience to new levels. To utilize this rich set of capabilities, one must convert the model into a graph and store it in a graph database with no significant loss of information. Applying the appropriate algorithms and translating the query response back to the original intelligible and meaningful diagrammatic and textual model representation is most valuable. We present and demonstrate a querying approach of converting Object-Process Methodology (OPM) ISO 19450 models into graphs, storing them in a Neo4J graph database, and performing queries that answer complex questions on various system aspects, providing key insights into the modeled system or phenomenon and helping to improve the system design

Loss of E2F7 expression is an early event in squamous differentiation and causes derepression of the key differentiation activator Sp1

Squamous differentiation is controlled by key transcription factors such as Sp1 and E2F. We have previously shown that E2F1 can suppress transcription of the differentiation-specific gene, transglutaminase type 1 (TG1), by an indirect mechanism mediated by Sp1. Transient transfection of E2F1-E2F6 indicated that E2F-mediated reduction of Sp1 transcription was not responsible for E2F-mediated suppression of squamous differentiation. However, we found that E2F4 and E2F7, but not E2Fs 1, 2, 3, 5, or 6, could suppress the activation of the Sp1 promoter in differentiated keratinocytes (KCs). E2F4-mediated suppression could not be antagonized by E2Fs 1, 2, 3, 5, or 6 and was localized to a region of the human Sp1 promoter spanning-139 to +35 bp. Chromatin immunoprecipitation analysis, as well as transient overexpression and short hairpin RNA knockdown experiments indicate that E2F7 binds to a unique binding site located between-139 and-119 bp of the Sp1 promoter, and knockdown of E2F7 in proliferating KCs leads to a derepression of Sp1 expression and the induction of TG1. In contrast, E2F4 knockdown in proliferating KCs did not alter Sp1 expression. These data indicate that loss of E2F7 during the initiation of differentiation leads to the derepression of Sp1 and subsequent transcription of differentiation-specific genes such as TG1