A study of the elements copper through uranium in Sirius A: Contributions from STIS and ground-based spectra

We determine abundances or upper limits for all of the 55 stable elements from copper to uranium for the A1 Vm star Sirius. The purpose of the study is to assemble the most complete picture of elemental abundances with the hope of revealing the chemical history of the brightest star in the sky, apart from the Sun. We also explore the relationship of this hot metallic-line (Am) star to its cooler congeners, as well as the hotter, weakly- or non-magnetic mercury-manganese (HgMn) stars. Our primary observational material consists of {\em Hubble Space Telescope} ($HST$) spectra taken with the Space Telescope Imaging Spectrograph (STIS) in the ASTRAL project. We have also used archival material from the %\citep/{ayr10}. $COPERNICUS$ satellite, and from the $HST$ Goddard High-Resolution Spectrograph (GHRS), as well as ground-based spectra from Furenlid, Westin, Kurucz, Wahlgren, and their coworkers, ESO spectra from the UVESPOP project, and NARVAL spectra retrieved from PolarBase. Our analysis has been primarily by spectral synthesis, and in this work we have had the great advantage of extensive atomic data unavailable to earlier workers. We find most abundances as well as upper limits range from 10 to 100 times above solar values. We see no indication of the huge abundance excesses of 1000 or more that occur among many chemically peculiar (CP) stars of the upper main sequence. The picture of Sirius as a hot Am star is reinforced.Comment: With 6 Figures and 4 Tables; accepted for publication in Ap

Polarizations and differential calculus in affine spaces

Within the framework of mappings between affine spaces, the notion of $n$-th polarization of a function will lead to an intrinsic characterization of polynomial functions. We prove that the characteristic features of derivations, such as linearity, iterability, Leibniz and chain rules, are shared -- at the finite level -- by the polarization operators. We give these results by means of explicit general formulae, which are valid at any order $n$, and are based on combinatorial identities. The infinitesimal limits of the $n$-th polarizations of a function will yield its $n$-th derivatives (without resorting to the usual recursive definition), and the above mentioned properties will be recovered directly in the limit. Polynomial functions will allow us to produce a coordinate free version of Taylor's formula

A large stellar evolution database for population synthesis studies. II. Stellar models and isochrones for an alpha-enhanced metal distribution

[Abridged] We present a large, new set of stellar evolution models and isochrones for an alpha-enhanced metal distribution typical of Galactic halo and bulge stars; it represents a homogeneous extension of our stellar model library for a distribution already presented in Pietrinferni et al.(2004). The effect of the alpha-element enhancement has been properly taken into account in the nuclear network, opacity, equation of state and, for the first time, the bolometric corrections, and color transformations. This allows us to avoid the inconsistent use - common to all alpha-enhanced model libraries currently available - of scaled-solar bolometric corrections and color transformations for alpha-enhanced models and isochrones. We show how bolometric corrections to magnitudes obtained for the U,B portion of stellar spectra for T_{eff}<=6500K, are significantly affected by the metal mixture, especially at the higher metallicities. We also provide complete sets of evolutionary models for low-mass, He-burning stellar structures covering the whole metallicity range, to enable synthetic horizontal branch simulations. We compare our database with several widely used stellar model libraries from different authors, as well as with various observed color magnitude and color-color diagrams (Johnson-Cousins BVI and near infrared magnitudes, Stromgren colors) of Galactic field stars and globular clusters. We also test our isochrones comparing integrated optical colors and Surface Brightness Fluctuation magnitudes with selected globular cluster data. We find a general satisfactory agreement with the empirical constraints.Comment: 46 pages, 20 figures, ApJ in press, the whole database presented in this paper can be foud at http://www.te.astro.it/BASTI/index.ph

Systematic screening as a strategy to increase services integration and revenues in Honduras

This operations research study, undertaken by the Honduras Family Planning Association (Asociación Hondureña de Planificación de Familia—ASHONPLAFA), tested the effectiveness of systematic screening to increase the number of services and revenue per visit in a reproductive health program. Despite monitoring plans, provider compliance with the intervention was low; the overall proportion of clients screened was less than 11 percent, and the frequency of screening varied greatly by clinic contact point. Although the study did not show an increase in the mean number of services per client, the negative results could reasonably be attributed to lack of implementation of the intervention. After consultation with the ASHONPLAFA marketing department, the executive director ordered that the strategy be implemented in all clinics, along with a system to monitor the utilization of a simplified screening form, designed to be less time consuming and less intrusive than the form tested during the experiment. The new form is limited to services most likely to be needed by clients, as indicated by the study’s analysis of unmet need and potential demand

Phosphoinositide 3-kinase δ inhibition promotes antitumor responses but antagonizes checkpoint inhibitors.

Multiple modes of immunosuppression restrain immune function within tumors. We previously reported that phosphoinositide 3-kinase δ (PI3Kδ) inactivation in mice confers resistance to a range of tumor models by disrupting immunosuppression mediated by regulatory T cells (Tregs). The PI3Kδ inhibitor idelalisib has proven highly effective in the clinical treatment of chronic lymphocytic leukemia and the potential to extend the use of PI3Kδ inhibitors to nonhematological cancers is being evaluated. In this work, we demonstrate that the antitumor effect of PI3Kδ inactivation is primarily mediated through the disruption of Treg function, and correlates with tumor dependence on Treg immunosuppression. Compared with Treg-specific PI3Kδ deletion, systemic PI3Kδ inactivation is less effective at conferring resistance to tumors. We show that PI3Kδ deficiency impairs the maturation and reduces the capacity of CD8+ cytotoxic T lymphocytes (CTLs) to kill tumor cells in vitro, and to respond to tumor antigen-specific immunization in vivo. PI3Kδ inactivation antagonized the antitumor effects of tumor vaccines and checkpoint blockade therapies intended to boost the CD8+ T cell response. These findings provide insights into mechanisms by which PI3Kδ inhibition promotes antitumor immunity and demonstrate that the mechanism is distinct from that mediated by immune checkpoint blockade.ELL was supported by the Yousef Jameel Scholarship (Cambridge Trust). DG was funded by a grant from Karus Therapeutics Ltd. RR and KO received institute support from Biotechnology and Biological Sciences Research Council (BBSRC) BBS/E/B/000C0407, - C0409, -C0427 and -C0428 and project grant BB/N007794/1. RR was supported by Wellcome Trust grant 105663/Z/14/Z. KO was also supported by Wellcome Trust grant 095198/Z/10/Z

Mitogen-activated kinase kinase kinase 1 inhibits hedgehog signaling and medulloblastoma growth through GLI1 phosphorylation

The aberrant activation of hedgehog (HH) signaling is a leading cause of the development of medulloblastoma, a pediatric tumor of the cerebellum. The FDA‑approved HH inhibitor, Vismodegib, which targets the transmembrane transducer SMO, has shown limited efficacy in patients with medulloblastoma, due to compensatory mechanisms that maintain an active HH‑GLI signaling status. Thus, the identification of novel actionable mechanisms, directly affecting the activity of the HH‑regulated GLI transcription factors is an important goal for these malignancies. In this study, using gene expression and reporter assays, combined with biochemical and cellular analyses, we demonstrate that mitogen‑activated kinase kinase kinase&nbsp;1&nbsp;(MEKK1), the most upstream kinase of the mitogen‑activated protein kinase&nbsp;(MAPK) phosphorylation modules, suppresses HH signaling by associating and phosphorylating GLI1, the most potent HH‑regulated transcription factor. Phosphorylation occurred at multiple residues in the C‑terminal region of GLI1 and was followed by an increased association with the cytoplasmic proteins&nbsp;14‑3‑3. Of note, the enforced expression of MEKK1 or the exposure of medulloblastoma cells to the MEKK1 activator, Nocodazole, resulted in a marked inhibitory effect on GLI1 activity and tumor cell proliferation and viability. Taken together, the results of this study shed light on a novel regulatory mechanism of HH signaling, with potentially relevant implications in cancer therapy