The Public Repository of Xenografts enables discovery and randomized phase II-like trials in mice

More than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publicly available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment, called the Public Repository of Xenografts (PRoXe). PRoXe includes all de-identified information relevant to the primary specimens and the PDXs derived from them. Using this repository, we demonstrate that large studies of acute leukemia PDXs that mimic human randomized clinical trials can characterize drug efficacy and generate transcriptional, functional, and proteomic biomarkers in both treatment-naive and relapsed/refractory disease

Early carboniferous brachiopod faunas from the Baoshan block, west Yunnan, southwest China

38 brachiopod species in 27 genera and subgenera are described from the Yudong Formation in the Shidian-Baoshan area, west Yunnan, southwest China. New taxa include two new subgenera: Unispirifer (Septimispirifer) and Brachythyrina (Longathyrina), and seven new species: Eomarginifera yunnanensis, Marginatia cylindrica, Unispirifer (Unispirifer) xiangshanensis, Unispirifer (Septimispirifer) wafangjieensis, Brachythyrina (Brachythyrina) transversa, Brachythyrina (Longathyrina) baoshanensis, and Girtyella wafangjieensis. Based on the described material and constraints from associated coral and conodont faunas, the age of the brachiopod fauna from the Yudon Formation is considered late Tournaisian (Early Carboniferous), with a possibility extending into earlyViseacutean.<br /

Similar T-Cell Immune Responses Induced by Group M Consensus Env Immunogens with Wild-Type or Minimum Consensus Variable Regions

Consensus HIV-1 genes can decrease the genetic distances between candidate immunogens and field virus strains. To ensure the functionality and optimal presentation of immunologic epitopes, we generated two group-M consensus env genes that contain variable regions either from a wild-type B/C recombinant virus isolate (CON6) or minimal consensus elements (CON-S) in the V1, V2, V4, and V5 regions. C57BL/6 and BALB/c mice were primed twice with CON6, CON-S, and subtype control (92UG37_A and HXB2/Bal_B) DNA and boosted with recombinant vaccinia virus (rVV). Mean antibody titers against 92UG37_A, 89.6_B, 96ZM651_C, CON6, and CON-S Env protein were determined. Both CON6 and CON-S induced higher mean antibody titers against several of the proteins, as compared with the subtype controls. However, no significant differences were found in mean antibody titers in animals immunized with CON6 or CON-S. Cellular immune responses were measured by using five complete Env overlapping peptide sets: subtype A (92UG37_A), subtype B (MN_B, 89.6_B and SF162_B), and subtype C (Chn19_C). The intensity of the induced cellular responses was measured by using pooled Env peptides; T-cell epitopes were identified by using matrix peptide pools and individual peptides. No significant differences in T-cell immune-response intensities were noted between CON6 and CON-S immunized BALB/c and C57BL/6 mice. In BALB/c mice, 10 and eight nonoverlapping T-cell epitopes were identified in CON6 and CON-S, whereas eight epitopes were identified in 92UG37_A and HXB2/BAL_B. In C57BL/6 mice, nine and six nonoverlapping T-cell epitopes were identified after immunization with CON6 and CON-S, respectively, whereas only four and three were identified in 92UG37_A and HXB2/BAL_B, respectively. When combined together from both mouse strains, 18 epitopes were identified. The group M artificial consensus env genes, CON6 and CON-S, were equally immunogenic in breadth and intensity for inducing humoral and cellular immune responses

Active wall conditioning through boron powder injection compatible ELM control in EAST

Real-time wall conditioning and edge-localized mode (ELM) suppression through real-time boron powder injection into high-confinement mode discharges of the Experimental Advanced Superconducting Tokamak (EAST) have been investigated. The boron powder injection effectively conditioned the plasma-facing components, as shown by the reductions in low-Z and high-Z impurities and the global recycling level in the whole inner vessel, and suppressed the strong magnetohydrodynamic (MHD) activity in the plasma core. The improved wall conditions also resulted in an earlier transition from L- to H-mode. Boron powder injection also effectively suppressed ELM in the lower single null configuration with BT in the favorable direction while leaving the plasma density and stored energy largely unaffected

Evolved massive stars at low-metallicity: I. A source catalog for the Small Magellanic Cloud

We present a clean, magnitude-limited (IRAC1 or WISE1 ≤ 15.0 mag) multiwavelength source catalog for the Small Magellanic Cloud (SMC) with 45 466 targets in total, with the purpose of building an anchor for future studies, especially for the massive star populations at low-metallicity. The catalog contains data in 50 different bands including 21 optical and 29 infrared bands, retrieved from SEIP, VMC, IRSF, AKARI, HERITAGE, Gaia, SkyMapper, NSC, Massey (2002, ApJS, 141, 81), and GALEX, ranging from the ultraviolet to the far-infrared. Additionally, radial velocities and spectral classifications were collected from the literature, and infrared and optical variability statistics were retrieved from WISE, SAGE-Var, VMC, IRSF, Gaia, NSC, and OGLE. The catalog was essentially built upon a 100 crossmatching and a 300 deblending between the Spitzer Enhanced Imaging Products (SEIP) source list and Gaia Data Release 2 (DR2) photometric data. Further constraints on the proper motions and parallaxes from Gaia DR2 allowed us to remove the foreground contamination. We estimate that about 99.5% of the targets in our catalog are most likely genuine members of the SMC. Using the evolutionary tracks and synthetic photometry from MESA Isochrones &amp; Stellar Tracks and the theoretical J - KS color cuts, we identified 1405 red supergiant (RSG), 217 yellow supergiant, and 1369 blue supergiant candidates in the SMC in five different color-magnitude diagrams (CMDs), where attention should also be paid to the incompleteness of our sample. We ranked the candidates based on the intersection of different CMDs. A comparison between the models and observational data shows that the lower limit of initial mass for the RSG population may be as low as 7 or even 6 M⊙ and that the RSG is well separated from the asymptotic giant branch (AGB) population even at faint magnitude, making RSGs a unique population connecting the evolved massive and intermediate stars, since stars with initial mass around 6 to 8 M⊙ are thought to go through a second dredge-up to become AGB stars. We encourage the interested reader to further exploit the potential of our catalog. © ESO 2019