RESUMEN
We present 87Sr/86Sr isotope ratios for ~1200 selected soil samples, collected by the GEMAS consortium from grazing (Gr) and agricultural (Ap) soils in Europe with the aim to better understand the strontium isotope distribution in the bioavailable fraction of the top-soil and its potential for provenancing applications. Spatial analysis shows that there is a clear distinction between coastal (<100â¯km) and non-coastal (>100â¯km) samples in their variance and that this variance is mirrored in the sodium concentration, suggesting an important but highly variable contribution from seaspray. We present two 87Sr/86Sr maps at 25â¯kmâ¯×â¯25â¯km scale: one based solely on the measured data using a classical kriging approach and one based on a Random Forest model using complementary GEMAS data to predict the strontium isotope composition at the remaining 3000+ GEMAS sampling locations, including appropriate uncertainty assessment. Using a forensic Bayesian likelihood ratio approach, a tool was developed in R to create provenancing likelihood ratio maps. The maps delineate areas of high and low likelihood and allow investigators to direct their resources to areas of interest. For actual forensic case work either the measured or the modelled data can be used as reference data for the overall distribution of 87Sr/86Sr values in Europe.
RESUMEN
Of patients with castrate resistant prostate cancer (CRPC), less than 25-33% survive more than five years. Recent studies have implicated estrogen, acting either alone or synergistically with androgens in the development of castrate resistant prostate cancer. Several in vitro and in vivo studies, as well as a limited number of clinical trials, have highlighted the potential of selective estrogen receptor modulators, such as raloxifene (Ral) for the treatment of castrate resistant prostate cancer. However, the poor oral bioavailability and metabolism of selective estrogen receptor modulators limit their efficiency in clinical application. To overcome these limitations, we have used styrene co-maleic acid (SMA) micelle to encapsulate raloxifene. Compared to free drug, SMA-Ral micelles had 132 and 140% higher cytotoxicity against PC3 and DU 145 prostate cell lines, respectively. SMA-Ral effectively inhibits cell cycle progression, increases apoptosis, and alters the integrity of tumor spheroid models. In addition, the micellar system induced changes in expression and localization of estrogen receptors, epidermal growth factor receptor (EGFR), and downstream effectors associated with cell proliferation and survival. Finally, SMA-Ral treatment decreased migration and invasion of castrate resistant prostate cancer cell lines. In conclusion, SMA-Ral micelles can potentially benefit new strategies for clinical management of castrate resistant prostate cancer.