A multi-modal data resource for investigating topographic heterogeneity in patient-derived xenograft tumors.

Patient-derived xenografts (PDXs) are an essential pre-clinical resource for investigating tumor biology. However, cellular heterogeneity within and across PDX tumors can strongly impact the interpretation of PDX studies. Here, we generated a multi-modal, large-scale dataset to investigate PDX heterogeneity in metastatic colorectal cancer (CRC) across tumor models, spatial scales and genomic, transcriptomic, proteomic and imaging assay modalities. To showcase this dataset, we present analysis to assess sources of PDX variation, including anatomical orientation within the implanted tumor, mouse contribution, and differences between replicate PDX tumors. A unique aspect of our dataset is deep characterization of intra-tumor heterogeneity via immunofluorescence imaging, which enables investigation of variation across multiple spatial scales, from subcellular to whole tumor levels. Our study provides a benchmark data resource to investigate PDX models of metastatic CRC and serves as a template for future, quantitative investigations of spatial heterogeneity within and across PDX tumor models

Accretion of gas by globular cluster stars

Some recent observations of the abundances of s-process, r-process, and alpha elements in metal-poor stars have led to a new scenario for their formation. According to this scenario, these stars were born in a globular cluster and accreted the s-process enriched gas expelled by cluster stars of higher-mass, thereby modifying their surface abundances. Later on, these polluted stars evaporated from the globular cluster to constitute an important fraction of the current halo population. In addition, there are now many direct observations of abundance anomalies not only in globular cluster giant stars but also in subgiant and main-sequence stars. Accretion provides again a plausible explanation for (at least some of) these peculiarities. Here we investigate further the efficiency of the accretion scenario. We find that in concentrated clusters with large escape velocities, accretion is very efficient and can indeed lead to major modifications of the stellar surface abundances.Comment: 11 pages; accepted for publication in Astronomy and Astrophysic

HIF1α Induces the Recruitment of Bone Marrow-Derived Vascular Modulatory Cells to Regulate Tumor Angiogenesis and Invasion

SummaryDevelopment of hypoxic regions is an indicator of poor prognosis in many tumors. Here, we demonstrate that HIF1α, the direct effector of hypoxia, partly through increases in SDF1α, induces recruitment of bone marrow-derived CD45+ myeloid cells containing Tie2+, VEGFR1+, CD11b+, and F4/80+ subpopulations, as well as endothelial and pericyte progenitor cells to promote neovascularization in glioblastoma. MMP-9 activity of bone marrow-derived CD45+ cells is essential and sufficient to initiate angiogenesis by increasing VEGF bioavailability. In the absence of HIF1α, SDF1α levels decrease, and fewer BM-derived cells are recruited to the tumors, decreasing MMP-9 and mobilization of VEGF. VEGF also directly regulates tumor cell invasiveness. When VEGF activity is impaired, tumor cells invade deep into the brain in the perivascular compartment

Mass transfer from a giant star to a main sequence companion and its contribution to long-orbital-period blue stragglers

Binary population synthesis shows that mass transfer from a giant star to a main-sequence (MS) companion may account for some observed long-orbital period blue stragglers. However, little attention {\bf is paid to this blue straggler formation scenario} as dynamical instability often happens when the mass donor is a giant star. In this paper, we have studied the critical mass ratio, $q_{\rm c}$, for dynamically stable mass transfer from a giant star to a MS companion using detailed evolution calculations. The results show that a more evolved star is generally less stable for Roche lobe overflow. Meanwhile, $q_{\rm c}$ almost linearly increases with the amount of the mass and angular momentum {\bf lost} during mass transfer, but has little dependance on stellar wind. To conveniently use the result, we give a fit of $q_{\rm c}$ as a function of the stellar radius at the onset of Roche lobe overflow and of the mass transfer efficiency during the Roche lobe overflow. To examine the formation of blue stragglers from mass transfer between giants and MS stars, we have performed Monte Carlo simulations with various $q_{\rm c}$. {\bf The simulations show that some binaries with the mass donor on the first giant branch may contribute to blue stragglers with $q_{\rm c}$ obtained in this paper but will not from previous $q_{\rm c}$. Meanwhile, from our $q_{\rm c}$, blue stragglers from the mass transfer between an AGB star and a MS companion may be more numerous and have a wider range of orbital periods than those from the other $q_{\rm c}$.Comment: 16 pages, 17 figures. accepted by MNRA

Fundamental Parameters and Abundances of Metal-Poor Stars: The SDSS Standard BD +17 4708

The atmospheric parameters and iron abundance of the Sloan Digital Sky Survey (SDSS) spectrophotometric standard star BD +17 4708 are critically examined using up-to-date Kurucz model atmospheres, LTE line formation calculations, and reliable atomic data. We find Teff = 6141+-50 K, log g = 3.87+-0.08, and [Fe/H]=-1.74+-0.09. The line-of-sight interstellar reddening, bolometric flux, limb-darkened angular diameter, stellar mass, and the abundances of Mg, Si, and Ca are also obtained. This star is a unique example of a moderately metal-poor star for which the effective temperature can be accurately constrained from the observed spectral energy distribution (corrected for reddening). Such analysis leads to a value that is higher than most spectroscopic results previously reported in the literature (~5950 K). We find that the ionization balance of Fe lines is satisfied only if a low Teff (~5950 K) is adopted. With our preferred Teff (6141 K), the mean iron abundance we obtain from the FeII lines is lower by about 0.15 dex than that from the FeI lines, and therefore, the discrepancy between the mean iron abundance from FeI and FeII lines cannot be explained by overionization by UV photons as the main non-LTE effect. We also comment on non-LTE effects and the importance of inelastic collisions with neutral H atoms in the determination of oxygen abundances in metal-poor stars from the 777 nm OI triplet. (Abridged)Comment: A&A in pres