Mean energy balance in the tropical Pacific Ocean

The maintenance of the ocean general circulation requires energy input from the wind. Previous studies estimate that the mean rate of wind work (or wind power) acting on the surface currents over the global ocean amounts to 1.1 TW (1 TW = 1012 Watts), though values remain highly uncertain. By analyzing the output from a range of ocean-only models and data assimilations, we show that the tropical Pacific Ocean contributes around 0.2 to 0.4 TW, which is roughly half of the total tropical contribution. Not only does this wind power represent a significant fraction of the total global energy input into the ocean circulation, it is also critical in maintaining the east-west tilt of the ocean thermocline along the equator. The differences in the wind power estimates are due to discrepancies in the wind stress used to force the models and discrepancies in the surface currents the models simulate, particularly the North Equatorial Counter Current and the South Equatorial Current. Decadal variations in the wind power, more prominent in some models, show a distinct decrease in the wind power in the late 1970s, consistent with the climate regime shift of that time and a flattening of the equatorial thermocline. We find that most of the wind power generated in the tropics is dissipated by friction in the mixed layer and in zonal currents with strong vertical and horizontal shears. Roughly 10 to 20% of the wind power (depending on the model) is transferred down the water column through vertical buoyancy fluxes to maintain the thermocline slope along the equator. Ultimately, this fraction of the wind power is dissipated by a combination of vertical and horizontal diffusion, energy advection out of the tropics, and damping by surface heat fluxes. Values of wind power generated in the tropical Pacific by coupled general circulation models are typically larger than those generated by ocean-only models, and range from 0.3 to 0.6 TW. Even though many models simulate a \u27realistic\u27 climate in the tropical ocean, their energy budgets can still vary greatly from one model to the next. We argue that a correct energy balance is an essential measure of how well the models represent the actual ocean physics

Spatial and temporal agreement in climate model simulations of the Interdecadal Pacific Oscillation

Accelerated warming and hiatus periods in the long-term rise of Global Mean Surface Temperature (GMST) have, in recent decades, been associated with the Interdecadal Pacific Oscillation (IPO). Critically, decadal climate prediction relies on the skill of state-of-the-art climate models to reliably represent these low-frequency climate variations. We undertake a systematic evaluation of the simulation of the IPO in the suite of Coupled Model Intercomparison Project 5 (CMIP5) models. We track the IPO in pre-industrial (control) and all-forcings (historical) experiments using the IPO tripole index (TPI). The TPI is explicitly aligned with the observed spatial pattern of the IPO, and circumvents assumptions about the nature of global warming. We find that many models underestimate the ratio of decadal-to-total variance in sea surface temperatures (SSTs). However, the basin-wide spatial pattern of positive and negative phases of the IPO are simulated reasonably well, with spatial pattern correlation coefficients between observations and models spanning the range 0.4–0.8. Deficiencies are mainly in the extratropical Pacific. Models that better capture the spatial pattern of the IPO also tend to more realistically simulate the ratio of decadal to total variance. Of the 13% of model centuries that have a fractional bias in the decadal-to-total TPI variance of 0.2 or less, 84% also have a spatial pattern correlation coefficient with the observed pattern exceeding 0.5. This result is highly consistent across both IPO positive and negative phases. This is evidence that the IPO is related to one or more inherent dynamical mechanisms of the climate system

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H

A many-analysts approach to the relation between religiosity and well-being

The relation between religiosity and well-being is one of the most researched topics in the psychology of religion, yet the directionality and robustness of the effect remains debated. Here, we adopted a many-analysts approach to assess the robustness of this relation based on a new cross-cultural dataset (N=10,535 participants from 24 countries). We recruited 120 analysis teams to investigate (1) whether religious people self-report higher well-being, and (2) whether the relation between religiosity and self-reported well-being depends on perceived cultural norms of religion (i.e., whether it is considered normal and desirable to be religious in a given country). In a two-stage procedure, the teams first created an analysis plan and then executed their planned analysis on the data. For the first research question, all but 3 teams reported positive effect sizes with credible/confidence intervals excluding zero (median reported β=0.120). For the second research question, this was the case for 65% of the teams (median reported β=0.039). While most teams applied (multilevel) linear regression models, there was considerable variability in the choice of items used to construct the independent variables, the dependent variable, and the included covariates

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

Future changes to the Indonesian Throughflow and Pacific circulation : The differing role of wind and deep circulation changes

Climate models consistently project a substantial decrease in the Indonesian Throughflow (ITF) in response to enhanced greenhouse warming. On interannual timescales ITF changes are largely related to tropical Pacific wind variability. However, on the multidecadal timescales investigated here we demonstrate that regional winds and associated changes in the upper ocean circulation cannot explain the projected ITF decrease. Instead, the decrease is related to a weakening in the northward flow of deep waters entering the Pacific basin at ~40°S and an associated reduction in the net basin-wide upwelling to the north of the southern tip of Australia. This can be traced back to consistent changes in the Antarctic Circumpolar Current and Southern Ocean overturning, although questions still remain as to the ultimate drivers. In contrast to the ITF decrease, substantial projected changes to the upper ocean circulation of the Pacific basin are well explained by robust changes in the surface winds