Catastrophic photometric redshift errors: weak lensing survey requirements

We study the sensitivity of weak lensing surveys to the effects of catastrophic redshift errors - cases where the true redshift is misestimated by a significant amount. To compute the biases in cosmological parameters, we adopt an efficient linearized analysis where the redshift errors are directly related to shifts in the weak lensing convergence power spectra. We estimate the number Nspec of unbiased spectroscopic redshifts needed to determine the catastrophic error rate well enough that biases in cosmological parameters are below statistical errors of weak lensing tomography. While the straightforward estimate of Nspec is ~10^6 we find that using only the photometric redshifts with z<=2.5 leads to a drastic reduction in Nspec to ~30,000 while negligibly increasing statistical errors in dark energy parameters. Therefore, the size of spectroscopic survey needed to control catastrophic errors is similar to that previously deemed necessary to constrain the core of the z_s-z_p distribution. We also study the efficacy of the recent proposal to measure redshift errors by cross-correlation between the photo-z and spectroscopic samples. We find that this method requires ~10% a priori knowledge of the bias and stochasticity of the outlier population, and is also easily confounded by lensing magnification bias. The cross-correlation method is therefore unlikely to supplant the need for a complete spectroscopic redshift survey of the source population.Comment: 14 pages, 3 figure

Extensive Association of Functionally and Cytotopically Related mRNAs with Puf Family RNA-Binding Proteins in Yeast

Genes encoding RNA-binding proteins are diverse and abundant in eukaryotic genomes. Although some have been shown to have roles in post-transcriptional regulation of the expression of specific genes, few of these proteins have been studied systematically. We have used an affinity tag to isolate each of the five members of the Puf family of RNA-binding proteins in Saccharomyces cerevisiae and DNA microarrays to comprehensively identify the associated mRNAs. Distinct groups of 40–220 different mRNAs with striking common themes in the functions and subcellular localization of the proteins they encode are associated with each of the five Puf proteins: Puf3p binds nearly exclusively to cytoplasmic mRNAs that encode mitochondrial proteins; Puf1p and Puf2p interact preferentially with mRNAs encoding membrane-associated proteins; Puf4p preferentially binds mRNAs encoding nucleolar ribosomal RNA-processing factors; and Puf5p is associated with mRNAs encoding chromatin modifiers and components of the spindle pole body. We identified distinct sequence motifs in the 3′-untranslated regions of the mRNAs bound by Puf3p, Puf4p, and Puf5p. Three-hybrid assays confirmed the role of these motifs in specific RNA–protein interactions in vivo. The results suggest that combinatorial tagging of transcripts by specific RNA-binding proteins may be a general mechanism for coordinated control of the localization, translation, and decay of mRNAs and thus an integral part of the global gene expression program

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

Auditory thresholds and tinnitus severity : the Blue Mountains Hearing Study

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The Importance of Motherhood among Women in the Contemporary United States

We contribute to feminist and gender scholarship on cultural notions of motherhood by analyzing the importance of motherhood among mothers and non-mothers. Using a national probability sample (N = 2,519) of U.S. women ages 25-45, we find a continuous distribution of scores measuring perceptions of the importance of motherhood among both groups. Employing OLS multiple regression, we examine why some women place more importance on motherhood, focusing on interests that could compete with valuing motherhood (e.g., education, work success, leisure), and controlling for characteristics associated with becoming a mother. Contrary to cultural schemas that view mother and worker identities as competing, we find that education level is not associated with the importance of motherhood for either group and that valuing work success is positively associated with valuing motherhood among mothers. Consistent with feminist explanations for delayed fertility, valuing leisure is negatively associated with valuing motherhood for non-mothers