Hepatic cancer stem cells (HCSCs) are considered as main players for the hepatocellular carcinoma (HCC) initiation, metastasis, drug resistance and recurrence. There is a growing evidence supporting the down-regulated miRNAs in HCSCs as key suppressors for the stemness traits, but still more details are vague about how these miRNAs modulate the HCC development. To uncover some of these miRNA regulatory aspects in HCSC, we compiled 15 down-regulated miRNA and their validated and predicted up-regulated targets in HCSC. The targets were enriched for several cancer cell stemness hallmarks and CSC pre-metastatic niche, which support these miRNAs role in suppression of HCSCs neoplastic transformation. Further, we constructed miRNA-Transcription factor (TF) regulatory networks, which provided new insights on the role of the proposed miRNA-TF co-regulation in the cancer stemness axis and its cross talk with the surrounding microenvironment. Our analysis revealed HCSC important hubs as candidate regulators for targeting hepatic cancer stemness such as, miR-148a, miR-214, E2F family, MYC and SLC7A5. Finally, we proposed a possible model for miRNA and TF co-regulation of HCSC signaling pathways. Our study identified an HCSC signature and set bridges between the reported results to give guide for future validation of HCC therapeutic strategies avoiding drug resistance.

No abstract

Abstract. In Cognitive Science, conceptual blending has been proposed as an important cognitive mechanism that facilitates the creation of new concepts and ideas by constrained combination of available knowledge. It thereby provides a possible theoretical foundation for modeling high-level cognitive faculties such as the ability to understand, learn, and create new concepts and theories. This paper describes a logic-based framework which allows a formal treatment of theory blending, discusses algorithmic aspects of blending within the framework, and provides an illustrating worked out example from mathematics.

In Cognitive Science, conceptual blending has been proposed as an important cognitive mechanism that facilitates the creation of new concepts and ideas by constrained combination of available knowledge. It thereby provides a possible theoretical foundation for modeling high-level cognitive faculties such as the ability to understand, learn, and create new concepts and theories. Quite often the development of new mathematical theories and results is based on the combination of previously independent concepts, potentially even originating from distinct subareas of mathematics. Conceptual blending promises to offer a framework for modeling and re-creating this form of mathematical concept invention with computational means. This paper describes a logic-based framework which allows a formal treatment of theory blending (a subform of the general notion of conceptual blending with high relevance for applications in mathematics), discusses an interactive algorithm for blending within the framework, and provides several illustrating worked examples from mathematics.