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

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

Tracking environmental changes of the Baltic Sea coastal zone since mid-Holocene

In this thesis, I used two coastal sediment sequences from SE Sweden to study how Baltic Sea coastal environment has changed since the mid-Holocene. The results show the coastal environment has been influenced by multi-stressors, such as climate change, shoreline regression and anthropogenic activities. Using the sediment sequence from Karlskrona Bay, past coastal environment between 7300 and 3500 cal. yr BP was reconstructed, with a focus on sea surface salinity (SSS). To quantitatively determine the SSS, two methods were employed: measurements of the 87Sr/86Sr ratios in carbonate shells (SSSSr) and the process length variations of dinoflagellate cysts Operculodinium centrocarpum (SSSpl). The SSSSr was ~6–7 between 6800 and 6400 cal. yr BP, similar to modern conditions. Between 6000 and 3900 cal. yr BP, SSSSr was consistently higher, with a range between 9 and 13. Microfossils sensitive to salinity variations, such as Radiosperma corbiforum and Spiniferites spp., supported the SSSSr estimate. The recorded salinity variations were most likely caused by climate changes in the Baltic Sea region. In comparison with the SSSSr, the SSSpl values were not as reliable and the process length-based method overestimated the salinity. Environmental conditions for the past 5,400 years at Gåsfjärden were reconstructed, with a focus on bottom water oxygen condition. Between 5400 and 4100 cal. yr BP, hypoxic bottom water (O2<2 mg L-1) prevailed in Gåsfjärden, despite its large connection with the open sea. This extended hypoxic interval was most likely caused by a warm and dry climate during the Holocene Thermal Maximum. The most intense hypoxic interval was recorded between 4400 and 4100 cal. yr BP, and coincided with a similar hypoxic interval in the Baltic Sea deep basin. As regional climate became wetter and colder between 4100 and 2700 cal. yr BP, bottom water oxygen conditions improved and salinity decreased. The environment in Gåsfjärden changed to close to modern conditions after 2700 cal. yr BP, which was characterized by less hypoxia and lower salinity. The study shows that climate condition and hydrographic configuration have been important drivers to the hypoxia formation. I further explored the drivers for the sediment grain-size variations in Gåsfjärden. Over the last 5,400 years, relative sea level decreased 17 m in the region, caused by isostatic land uplift. As a consequence, Gåsfjärden changed gradually from a highly open coastal site into a semi-enclosed inlet surrounded with numerous islands. To examine whether the long-term coastal morphology changes in Gåsfjärden have had important impact on sediment grain-size, a digital elevation model-based openness index was calculated to quantitatively estimate the morphological changes. Between 5400 and 4400 cal. yr BP, Gåsfjärden was characterized with the highest openness index. During this interval, the highest sand content and silt/clay ratios were recorded, indicating relatively high hydrodynamic energy. The average sand content decreased to about 0.2% between 4400 and 200 cal. yr BP, caused by large openness decline. The maximum sand content has been less than 1% in the Gåsfjärden sediments, implying generally low hydrodynamic energy compared with other open coastal areas. Lastly the thesis studies the linkage between land use and coastal ecosystem over the last millennium. Pollen-based land cover for the Gåsfjärden catchment was reconstructed and I further compared it with paleoenvironmental variables from Gåsfjärden. Prior to 1800s, the minor changes in sedimentary diatom assemblages, C and N isotopes from the Gåsfjärden record were possibly caused by natural climate variations and small-scale anthropogenic activities. The onset of eutrophication in Gåsfjärden can be traced to the early 1800s and intensified land use is the main driver. Anthropogenic activities in the 20th century, mostly associated with agricultural expansion, have caused unprecedented ecosystem changes in the coastal inlet, as reflected in increased pelagic diatoms and the geochemistry proxies