External stakeholder risk response strategies selection in project portfolio.

To improve the effectiveness of external stakeholder risks (ESRs) management in project portfolios (PPs), a portfolio-wide risk response approach is required. However, current research is inadequate to effectively identify response strategies for ESRs, which brings challenges to managing ESRs in PPs. In this context, the purpose of this study is to select an appropriate combination of response strategies for ESRs by considering interactions among ESRs, projects, and response strategies in the PP. A Bayesian influence diagram (BID) coupled with a multi-objective optimization model is deemed suitable for this context. Firstly, a probability-sensitivity matrix is established to determine the key ESRs. Then, a BID is constructed to calculate the expected values of different combinations of response strategies. Finally, integrating stakeholder satisfaction and strategy cost, an optimization model for risk response strategy selection is established to obtain candidate combinations. By combining expected values and candidate combinations, the optimal strategy combination is selected. The proposed model comprehensively considers and evaluates the interactions between risks, projects, and risk responses. This enhances the desirability of expected outcomes and reduces project execution costs.

TICRR Contributes to Tumorigenesis Through Accelerating DNA Replication in Cancers.

DNA replication is precisely regulated in cells and its dysregulation can trigger tumorigenesis. Here we identified that the TOPBP1 interacting checkpoint and replication regulator (TICRR) mRNA level was universally and highly expressed in 15 solid cancer types. Depletion of TICRR significantly inhibited tumor cell growth, colony formation and migration in vitro, and strikingly inhibited tumor growth in the xenograft model. We reveal that knockdown of TICRR inhibited not only the initiation but also the fork progression of DNA replication. Suppression of DNA synthesis by TICRR silencing caused DNA damage accumulation, subsequently activated the ATM/CHK2 dependent p53 signaling, and finally induced cell cycle arrest and apoptosis at least in p53-wild cancer cells. Further, we show that a higher TICRR level was associated with poorer overall survival (OS) and disease free survival (DFS) in multiple cancer types. In conclusion, our study shows that TICRR is involved in tumorigenesis by regulating DNA replication, acting as a common biomarker for cancer prognosis and could be a promising target for drug-development and cancer treatment.