Long-term coastal openness variation and its impact on sediment grain-size distribution:a case study from the Baltic Sea

We analysed the long-term variations in grain-size distribution in sediments from Gåsfjärden, a fjordlike inlet in the southwestern Baltic Sea, and explored potential drivers of the recorded changes in the sediment grain-size data. Over the last 5.4 thousand years (ky) in the study region, the relative sea level decreased 17 m, which was caused by isostatic land uplift. As a consequence, Gåsfjärden was transformed from an open coastal setting to a semi-closed inlet surrounded by numerous small islands on the seaward side. To quantitatively estimate the morphological changes in Gåsfjärden over the investigated time period and to further link the changes to the grain-size distribution data, a digital elevation model (DEM)-based openness index was calculated. The largest values of the openness indices were found between 5.4 and 4.4 cal ka BP, which indicates relatively high bottom water energy. During the same period, the highest sand content (∼0.4 %) and silt / clay ratio (∼0.3) in the sediment sequence were also recorded. After 4.4 cal ka BP, the average sand content was halved to ∼0.2% and the silt / clay ratio showed a significant decreasing trend over the last 4 ky. These changes were found to be associated with the gradual embayment of Gåsfjärden, as represented by the openness indices. The silt / clay ratios exhibited a delayed and relatively slower change compared with the sand content, which indicates different grain-size sediment responses to the changes in hydrodynamic energy. Our DEM-based coastal openness indices have proved to be a useful tool for interpreting the temporal dynamics of sedimentary grain size

AOTree: Aspect Order Tree-based Model for Explainable Recommendation

Recent recommender systems aim to provide not only accurate recommendations but also explanations that help users understand them better. However, most existing explainable recommendations only consider the importance of content in reviews, such as words or aspects, and ignore the ordering relationship among them. This oversight neglects crucial ordering dimensions in the human decision-making process, leading to suboptimal performance. Therefore, in this paper, we propose Aspect Order Tree-based (AOTree) explainable recommendation method, inspired by the Order Effects Theory from cognitive and decision psychology, in order to capture the dependency relationships among decisive factors. We first validate the theory in the recommendation scenario by analyzing the reviews of the users. Then, according to the theory, the proposed AOTree expands the construction of the decision tree to capture aspect orders in users' decision-making processes, and use attention mechanisms to make predictions based on the aspect orders. Extensive experiments demonstrate our method's effectiveness on rating predictions, and our approach aligns more consistently with the user' s decision-making process by displaying explanations in a particular order, thereby enhancing interpretability

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival