Internally heated and fully compressible convection: flow morphology and scaling laws

In stars and planets natural processes heat convective flows in the bulk of a convective region rather than at hard boundaries. By characterizing how convective dynamics are determined by the strength of an internal heating source we can gain insight into the processes driving astrophysical convection. Internally heated convection has been studied extensively in incompressible fluids, but the effects of stratification and compressibility have not been examined in detail. In this work, we study fully compressible convection driven by a spatially uniform heating source in 2D and 3D Cartesian, hydrodynamic simulations. We use a fixed temperature upper boundary condition which results in a system that is internally heated in the bulk and cooled at the top. We find that the flow speed, as measured by the Mach number, and turbulence, as measured by the Reynolds number, can be independently controlled by separately varying the characteristic temperature gradient from internal heating and the diffusivities. 2D simulations at a fixed Mach number (flow speed) demonstrate consistent power at low wavenumber as diffusivities are decreased. We observe convection where the velocity distribution is skewed towards cold, fast downflows, and that the flow speed is related to the length scale and entropy gradient of the upper boundary where the downflows are driven. We additionally find a heat transport scaling law which is consistent with prior incompressible work.Comment: 22 pages, 12 figures, submitted to Phys. Rev. Fluid

Marine Ecoregion and Deepwater Horizon Oil Spill Affect Recruitment and Population Structure of a Salt Marsh Snail

Marine species with planktonic larvae often have high spatial and temporal variation in recruitment that leads to subsequent variation in the ecology of benthic adults. Using a combination of published and unpublished data, we compared the population structure of the salt marsh snail, Littoraria irrorata, between the South Atlantic Bight and the Gulf Coast of the United States to infer geographic differences in recruitment and to test the hypothesis that the Deepwater Horizon oil spill led to widespread recruitment failure of L. irrorata in Louisiana in 2010. Size-frequency distributions in both ecoregions were bimodal, with troughs in the distributions consistent with a transition from sub-adults to adults at ~13 mm in shell length as reported in the literature; however, adult snails reached larger sizes in the Gulf Coast. The ratio of sub-adults to adults was 1.5–2 times greater in the South Atlantic Bight than the Gulf Coast, consistent with higher recruitment rates in the South Atlantic Bight. Higher recruitment rates in the South Atlantic Bight could contribute to higher snail densities and reduced adult growth in this region. The ratio of sub-adults to adults in Louisiana was lower in 2011 than in previous years, and began to recover in 2012–2014, consistent with widespread recruitment failure in 2010, when large expanses of spilled oil were present in coastal waters. Our results reveal an important difference in the ecology of a key salt marsh invertebrate between the two ecoregions, and also suggest that the Deepwater Horizon oil spill may have caused widespread recruitment failure in this species and perhaps others with similar planktonic larval stages

Registered Ship Notes

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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

Infection with chikungunya virus confers heterotypic cross-neutralizing antibodies and memory B-cells against other arthritogenic alphaviruses predominantly through the B domain of the E2 glycoprotein.

Infections with Chikungunya virus, a mosquito-borne alphavirus, cause an acute febrile syndrome often followed by chronic arthritis that persists for months to years post-infection. Neutralizing antibodies are the primary immune correlate of protection elicited by infection, and the major goal of vaccinations in development. Using convalescent blood samples collected from both endemic and non-endemic human subjects at multiple timepoints following suspected or confirmed chikungunya infection, we identified antibodies with broad neutralizing properties against other alphaviruses within the Semliki Forest complex. Cross-neutralization generally did not extend to the Venezuelan Equine Encephalitis virus (VEEV) complex, although some subjects had low levels of VEEV-neutralizing antibodies. This suggests that broadly neutralizing antibodies elicited following natural infection are largely complex restricted. In addition to serology, we also performed memory B-cell analysis, finding chikungunya-specific memory B-cells in all subjects in this study as remotely as 24 years post-infection. We functionally assessed the ability of memory B-cell derived antibodies to bind to chikungunya virus, and related Mayaro virus, as well as the highly conserved B domain of the E2 glycoprotein thought to contribute to cross-reactivity between related Old-World alphaviruses. To specifically assess the role of the E2 B domain in cross-neutralization, we depleted Mayaro and Chikungunya virus E2 B domain specific antibodies from convalescent sera, finding E2B depletion significantly decreases Mayaro virus specific cross-neutralizing antibody titers with no significant effect on chikungunya virus neutralization, indicating that the E2 B domain is a key target of cross-neutralizing and potentially cross-protective neutralizing antibodies

Natural variation in cardiac metabolism and gene expression in Fundulus heteroclitus

Individual variation in gene expression is important for evolutionary adaptation1,2 and susceptibility to diseases and pathologies3,4. In this study, we address the functional importance of this variation by comparing cardiac metabolism to patterns of mRNA expression using microarrays. There is extensive variation in both cardiac metabolism and the expression of metabolic genes among individuals of the teleost fish Fundulus heteroclitus from natural outbred populations raised in a common environment: metabolism differed among individuals by a factor of more than 2, and expression levels of 94% of genes were significantly different (P < 0.01) between individuals in a population. This unexpectedly high variation in metabolic gene expression explains much of the variation in metabolism, suggesting that it is biologically relevant. The patterns of gene expression that are most important in explaining cardiac metabolism differ between groups of individuals. Apparently, the variation in metabolism seems to be related to different patterns of gene expression in the different groups of individuals. The magnitude of differences in gene expression in these groups is not important; large changes in expression have no greater predictive value than small changes. These data suggest that variation in physiological performance is related to the subtle variation in gene expression and that this relationship differs among individuals