Evidence for a general species time arearelationship

The species-area relationship (SAR) plays a central role in biodiversity research, and recent work has increased awareness of its temporal analog, the species-time relationship (STR). Here we provide evidence for a general species-time-area-relationship (STAR), in which species number is a function of the area and time span of sampling, as well as their interaction. For eight assemblages ranging from lake zooplankton to desert rodents, this model outperformed a sampling-based model and two simpler models in which area and time had independent effects. In every case the interaction term was negative, meaning that rates of species accumulation in space decreased with the time span of sampling, while species accumulation rates in time decreased with area sampled. Although questions remain about its precise functional form, the STAR provides a tool for scaling species richness across time and space, for comparing the relative rates of species turnover in space and time at different scales of sampling, and for rigorous testing of mechanisms proposed to drive community dynamics. Our results show that the SAR and STR are not separate relationships but two dimensions of one unified pattern. Keywords: community dynamics, spatiotemporal scaling, species diversity, turnover, speciesarea relationship, species-time relationshi

BIOSAFETY. Safeguarding gene drive experiments in the laboratory.

Multiple stringent confinement strategies should be used whenever possibleThis is the author accepted manuscript. The final version is available from AAAS via http://dx.doi.org/10.1126/science.aac793

Securitization in East Asia

Securitization offers a range of benefits for Asia's financial systems and economies as a mechanism to assist funding and investment. As a form of structured finance, reliable and efficient securitization can assist development by enabling financial systems to deepen and strengthen - thus contributing to overall economic growth and stability. It must be recognized, however, that there are both overt and more subtle risks in certain uses of securitization. The credit and liquidity crisis that began in the United States and spread to other developed financial systems in mid-2007 exposed the danger associated with securitization: excessive risk-taking or regulatory capital arbitrage rather than a tool to assist more conventional or conservative approaches to funding, risk management, or investment. Securitization has also been criticized for rendering financial markets opaque, while contributing to a growing emphasis in the global economy of credit intermediation conducted in capital markets rather than through banks. This study examines the institutional basis of these concerns by investigating the use of securitization in East Asia, questioning both the growth in regional activity since the 1997/98 Asian financial crisis, and the reasons for it remaining constrained. The paper concludes with a discussion of proposals to support proper development of securitization in the region, including institutional mechanisms that could better allow securitization to enhance development and financial stability. If East Asia begins to make fuller use of securitization, its motive will be to meet funding or investment needs in the real economy rather than balance sheet arbitrage of the kind that peaked elsewhere in 2007

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

The impact of heat on kidney stone presentations in South Carolina under two climate change scenarios.

The risk of kidney stone presentations increases after hot days, likely due to greater insensible water losses resulting in more concentrated urine and altered urinary flow. It is thus expected that higher temperatures from climate change will increase the global prevalence of kidney stones if no adaptation measures are put in place. This study aims to quantify the impact of heat on kidney stone presentations through 2089, using South Carolina as a model state. We used a time series analysis of historical kidney stone presentations (1997-2014) and distributed lag non-linear models to estimate the temperature dependence of kidney stone presentations, and then quantified the projected impact of climate change on future heat-related kidney stone presentations using daily projections of wet-bulb temperatures to 2089, assuming no adaptation or demographic changes. Two climate change models were considered-one assuming aggressive reduction in greenhouse gas emissions (RCP 4.5) and one representing uninibited greenhouse gas emissions (RCP 8.5). The estimated total statewide kidney stone presentations attributable to heat are projected to increase by 2.2% in RCP 4.5 and 3.9% in RCP 8.5 by 2085-89 (vs. 2010-2014), with an associated total excess cost of ~ $57 million and ~$99 million, respectively

Helicase-like transcription factor expression is associated with a poor prognosis in Non-Small-Cell Lung Cancer (NSCLC)

Abstract Background The relapse rate in early stage non-small cell lung cancer (NSCLC) after surgical resection is high. Prognostic biomarkers may help identify patients who may benefit from additional therapy. The Helicase-like Transcription Factor (HLTF) is a tumor suppressor, altered in cancer either by gene hypermethylation or mRNA alternative splicing. This study assessed the expression and the clinical relevance of wild-type (WT) and variant forms of HLTF RNAs in NSCLC. Methods We analyzed online databases (TCGA, COSMIC) for HLTF alterations in NSCLC and assessed WT and spliced HLTF mRNAs expression by RT-ddPCR in 39 lung cancer cell lines and 171 patients with resected stage I-II NSCLC. Results In silico analyses identified HLTF gene alterations more frequently in lung squamous cell carcinoma than in adenocarcinoma. In cell lines and in patients, WT and I21R HLTF mRNAs were detected, but the latter at lower level. The subgroup of 25 patients presenting a combined low WT HLTF expression and a high I21R HLTF expression had a significantly worse disease-free survival than the other 146 patients in univariate (HR 1.96, CI 1.17–3.30; p = 0.011) and multivariate analyses (HR 1.98, CI 1.15–3.40; p = 0.014). Conclusion A low WT HLTF expression with a high I21R HLTF expression is associated with a poor DFS