The ISB Cancer Genomics Cloud: A Flexible Cloud-Based Platform for Cancer Genomics Research.

The ISB Cancer Genomics Cloud (ISB-CGC) is one of three pilot projects funded by the National Cancer Institute to explore new approaches to computing on large cancer datasets in a cloud environment. With a focus on Data as a Service, the ISB-CGC offers multiple avenues for accessing and analyzing The Cancer Genome Atlas, TARGET, and other important references such as GENCODE and COSMIC using the Google Cloud Platform. The open approach allows researchers to choose approaches best suited to the task at hand: from analyzing terabytes of data using complex workflows to developing new analysis methods in common languages such as Python, R, and SQL; to using an interactive web application to create synthetic patient cohorts and to explore the wealth of available genomic data. Links to resources and documentation can be found at www.isb-cgc.or

Palaeolimnological evidence for an east-west climate see-saw in the Mediterranean since AD 900

During the period of instrumental records, the North Atlantic Oscillation (NAO) has strongly influenced inter-annual precipitation variations in the western Mediterranean, while some eastern parts of the basin have shown an anti-phase relationship in precipitation and atmospheric pressure. Here we explore how the NAO and other atmospheric circulation modes operated over the longer timescales of the Medieval Climate Anomaly (MCA) and Little Ice Age (LIA). High-resolution palaeolimnological evidence from opposite ends of the Mediterranean basin, supplemented by other palaeoclimate data, is used to track shifts in regional hydro-climatic conditions. Multiple geochemical, sedimentological, isotopic and palaeoecological proxies from Estanya and Montcortés lakes in northeast Spain and Nar lake in central Turkey have been cross-correlated at decadal time intervals since AD 900. These dryland lakes capture sensitively changes in precipitation/evaporation (P/E) balance by adjustments in water level and salinity, and are especially valuable for reconstructing variability over decadal-centennial timescales. Iberian lakes show lower water levels and higher salinities during the 11th to 13th centuries synchronous with the MCA and generally more humid conditions during the 'LIA' (15th-19th centuries). This pattern is also clearly evident in tree-ring records from Morocco and from marine cores in the western Mediterranean Sea. In the eastern Mediterranean, palaeoclimatic records from Turkey, Greece and the Levant show generally drier hydro-climatic conditions during the LIA and a wetter phase during the MCA. This implies that a bipolar climate see-saw has operated in the Mediterranean for the last 1100. years. However, while western Mediterranean aridity appears consistent with persistent positive NAO state during the MCA, the pattern is less clear in the eastern Mediterranean. Here the strongest evidence for higher winter season precipitation during the MCA comes from central Turkey in the northeastern sector of the Mediterranean basin. This in turn implies that the LIA/MCA hydro-climatic pattern in the Mediterranean was determined by a combination of different climate modes along with major physical geographical controls, and not by NAO forcing alone, or that the character of the NAO and its teleconnections have been non-stationary. © 2011 Elsevier B.V

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

Applying the analytic network process to disclose knowledge assets value creation dynamics

The recent literature grounded on the resource and knowledge-based view of the firm, has widely outlined the importance of knowledge assets as well as of the management approaches of their development. However, only few contributions have investigated the mechanisms by which these resources interact to sustain company’s value creation dynamics. In particular, there is a lack of approaches suitable to disentangle those mechanisms and to explain how knowledge assets cluster and interplay in improving organisational performance. A clear understanding of how knowledge assets take part in value creation allows to identify those knowledge assets which, due to their critical role in achieving the company’s performance objectives, need to be managed and appropriately exploited. This paper proposes a model, based on the analytic network process (ANP) methodology, to disclose and assess how knowledge assets mutually interact and take part in company’s value creation dynamics. The application of the ANP allows to reveal and to evaluate the dependencies and inter-dependencies linking knowledge assets to organisational performance objectives and to set priorities among knowledge assets against targeted performance. The application of the model is tested by its application to the identification of the knowledge assets value drivers at the basis of NPD performances improvement within an engineering company located in South of Italy

Five Stages of the Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE) trial

IDMC  = Independent Data Monitoring Committee; FFS  = failure-free survival; HR  = hazard ratio, where 0 ≤ d ≤ c ≤ b ≤ a ≤ 5.<p><b>Copyright information:</b></p><p>Taken from "Speeding up the Evaluation of New Agents in Cancer"</p><p></p><p>JNCI Journal of the National Cancer Institute 2008;100(17):1204-1214.</p><p>Published online 3 Sep 2008</p><p>PMCID:PMC2528020.</p><p></p