Coupled effects of local movement and global interaction on contagion

By incorporating segregated spatial domain and individual-based linkage into the SIS (susceptible-infected-susceptible) model, we investigate the coupled effects of random walk and intragroup interaction on contagion. Compared with the situation where only local movement or individual-based linkage exists, the coexistence of them leads to a wider spread of infectious disease. The roles of narrowing segregated spatial domain and reducing mobility in epidemic control are checked, these two measures are found to be conducive to curbing the spread of infectious disease. Considering heterogeneous time scales between local movement and global interaction, a log-log relation between the change in the number of infected individuals and the timescale $\tau$ is found. A theoretical analysis indicates that the evolutionary dynamics in the present model is related to the encounter probability and the encounter time. A functional relation between the epidemic threshold and the ratio of shortcuts, and a functional relation between the encounter time and the timescale $\tau$ are found

A generalized public goods game with coupling of individual ability and project benefit

Facing a heavy task, any single person can only make a limited contribution and team cooperation is needed. As one enjoys the benefit of the public goods, the potential benefits of the project are not always maximized and may be partly wasted. By incorporating individual ability and project benefit into the original public goods game, we study the coupling effect of the four parameters, the upper limit of individual contribution, the upper limit of individual benefit, the needed project cost and the upper limit of project benefit on the evolution of cooperation. Coevolving with the individual-level group size preferences, an increase in the upper limit of individual benefit promotes cooperation while an increase in the upper limit of individual contribution inhibits cooperation. The coupling of the upper limit of individual contribution and the needed project cost determines the critical point of the upper limit of project benefit, where the equilibrium frequency of cooperators reaches its highest level. Above the critical point, an increase in the upper limit of project benefit inhibits cooperation. The evolution of cooperation is closely related to the preferred group-size distribution. A functional relation between the frequency of cooperators and the dominant group size is found

Current perspectives on genotype classification and individualized drug targeting in triple-negative breast cancer

Triple negative breast cancer (TNBC), a special subset of breast cancer, refers to negative expressions of estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth receptor 2 (HER2). It is associated with extreme local recurrence and distant metastasis with highly invasive character. With advances in genomics, the bases of molecular classification of TNBC now include the heterogeneity of its expression at the molecular level and clinical pathology, apart from classical immunohistochemistry. Every subtype of TNBC has different individualized target drugs, which include epidermal growth factor receptor (EGFR) inhibitor, poly-AD-ribose polymerase (PARP) inhibitor, anthracycline or paclitaxel, immunotherapy and vascular endothelial growth factor receptor (VEGFR) inhibitor. Combinations of target drugs are also used. Thus, there are no widely recognized standards of genotype classification and individualized drug targeting in TNBC. In this review, relevant studies and latest developments on TNBC are presented.Keywords: Triple-negative breast cancer, Genotype classification, Individualized drug targeting, Breast cance

MAVS Is essential for primary CD4 + T cell immunity but not for recall T cell responses following an attenuated West Nile virus infection

ABSTRACT The use of pathogen recognition receptor (PRR) agonists and the molecular mechanisms involved have been the major focus of research in individual vaccine development. West Nile virus (WNV) nonstructural (NS) 4B-P38G mutant has several features for an ideal vaccine candidate, including significantly reduced neuroinvasiveness, induction of strong adaptive immunity, and protection of mice from wild-type (WT) WNV infection. Here, we determined the role of mitochondrial antiviral signaling protein (MAVS), the adaptor protein for RIG-I-like receptor in regulating host immunity against the NS4B-P38G vaccine. We found that Mavs −/− mice were more susceptible to NS4B-P38G priming than WT mice. Mavs −/− mice had a transiently reduced production of antiviral cytokines and an impaired CD4 + T cell response in peripheral organs. However, antibody and CD8 + T cell responses were minimally affected. NS4B-P38G induced lower type I interferon (IFN), IFN-stimulating gene, and proinflammatory cytokine responses in Mavs −/− dendritic cells and subsequently compromised the antigen-presenting capacity for CD4 + T cells. Interestingly, Mavs −/− mice surviving NS4B-P38G priming were all protected from a lethal WT WNV challenge. NS4B-P38G-primed Mavs −/− mice exhibited equivalent levels of protective CD4 + T cell recall response, a modestly reduced WNV-specific IgM production, but more robust CD8 + T cell recall response. Taken together, our results suggest that MAVS is essential for boosting optimal primary CD4 + T cell responses upon NS4B-P38G vaccination and yet is dispensable for host protection and recall T cell responses during secondary WT WNV infection. IMPORTANCE The production of innate cytokines induced by the recognition of pathogen recognition receptors (PRRs) via their cognate ligands are critical for enhancing antigen-presenting cell functions and influencing T cell responses during microbial infection. The use of PRR agonists and the underlying molecular mechanisms have been the major focus in individual vaccine development. Here, we determined the role of mitochondrial antiviral-signaling protein (MAVS), the adaptor protein for RIG-I like receptor in regulating host immunity against the live attenuated West Nile virus (WNV) vaccine strain, the nonstructural (NS) 4B-P38G mutant. We found that MAVS is important for boosting optimal primary CD4 + T cell response during NS4B-P38G vaccination. However, MAVS is dispensable for memory T cell development and host protection during secondary wild-type WNV infection. Overall, these results may be utilized as a paradigm to aid in the rational development of other efficacious live attenuated flavivirus vaccines