117 research outputs found
Physical characteristics and non-keplerian orbital motion of "propeller" moons embedded in Saturn's rings
We report the discovery of several large "propeller" moons in the outer part
of Saturn's A ring, objects large enough to be followed over the 5-year
duration of the Cassini mission. These are the first objects ever discovered
that can be tracked as individual moons, but do not orbit in empty space. We
infer sizes up to 1--2 km for the unseen moonlets at the center of the
propeller-shaped structures, though many structural and photometric properties
of propeller structures remain unclear. Finally, we demonstrate that some
propellers undergo sustained non-keplerian orbit motion. (Note: This arXiv
version of the paper contains supplementary tables that were left out of the
ApJL version due to lack of space).Comment: 9 pages, 4 figures; Published in ApJ
Assessment of ABT-263 activity across a cancer cell line collection leads to a potent combination therapy for small-cell lung cancer
BH3 mimetics such as ABT-263 induce apoptosis in a subset of cancer models. However, these drugs have shown limited clinical efficacy as single agents in small-cell lung cancer (SCLC) and other solid tumor malignancies, and rational combination strategies remain underexplored. To develop a novel therapeutic approach, we examined the efficacy of ABT-263 across >500 cancer cell lines, including 311 for which we had matched expression data for select genes. We found that high expression of the proapoptotic gene Bcl2-interacting mediator of cell death (BIM) predicts sensitivity to ABT-263. In particular, SCLC cell lines possessed greater BIM transcript levels than most other solid tumors and are among the most sensitive to ABT-263. However, a subset of relatively resistant SCLC cell lines has concomitant high expression of the antiapoptotic myeloid cell leukemia 1 (MCL-1). Whereas ABT-263 released BIM from complexes with BCL-2 and BCL-XL, high expression of MCL-1 sequestered BIM released from BCL-2 and BCL-XL, thereby abrogating apoptosis. We found that SCLCs were sensitized to ABT-263 via TORC1/2 inhibition, which led to reduced MCL-1 protein levels, thereby facilitating BIM-mediated apoptosis. AZD8055 and ABT-263 together induced marked apoptosis in vitro, as well as tumor regressions in multiple SCLC xenograft models. In a Tp53; Rb1 deletion genetically engineered mouse model of SCLC, the combination of ABT-263 and AZD8055 significantly repressed tumor growth and induced tumor regressions compared with either drug alone. Furthermore, in a SCLC patient-derived xenograft model that was resistant to ABT-263 alone, the addition of AZD8055 induced potent tumor regression. Therefore, addition of a TORC1/2 inhibitor offers a therapeutic strategy to markedly improve ABT-263 activity in SCLC.United States. Dept. of Defense (Grant W81-XWH-13-1-0323)National Cancer Institute (U.S.) (Cancer Center Support Grant P30-CA14051
Acute and Persistent Mycobacterium tuberculosis Infections Depend on the Thiol Peroxidase TPX
The macrophage is the natural niche of Mycobacterium tuberculosis infection. In order to combat oxidative and nitrosative stresses and persist in macrophages successfully, M. tuberculosis is endowed with a very efficient antioxidant complex. Amongst these antioxidant enzymes, TpX is the only one in M. tuberculosis with sequence homology to thiol peroxidase. Previous reports have demonstrated that the M. tuberculosis TpX protein functions as a peroxidase in vitro. It is the dominant antioxidant which protects M. tuberculosis against oxidative and nitrosative stresses. The level of the protein increases in oxidative stress. To determine the roles of tpx gene in M. tuberculosis survival and virulence in vivo, we constructed an M. tuberculosis strain lacking the gene. The characteristics of the mutant were examined in an in vitro stationary phase model, in response to stresses; in murine bone marrow derived macrophages and in an acute and an immune resistant model of murine tuberculosis. The tpx mutant became sensitive to H2O2 and NO compared to the wild type strain. Enzymatic analysis using bacterial extracts from the WT and the tpx mutant demonstrated that the mutant contains reduced peroxidase activity. As a result of this, the mutant failed to grow and survive in macrophages. The growth deficiency in macrophages became more pronounced after interferon-γ activation. In contrast, its growth was significantly restored in the macrophages of inducible nitric oxide synthase (iNOS or NOS2) knockout mice. Moreover, the tpx mutant was impaired in its ability to initiate an acute infection and to maintain a persistent infection. Its virulence was attenuated. Our results demonstrated that tpx is required for M. tuberculosis to deal with oxidative and nitrosative stresses, to survive in macrophages and to establish acute and persistent infections in animal tuberculosis models
Robust estimation of bacterial cell count from optical density
Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data
Mesures de la pauvreté et politiques sociales : une étude comparative de la France, de la RFA et du Royaume-Uni
Statistics of « 44 million in poverty in Europe » have been widely reported, and figures for the proportion in poverty in different countries have entered debates about the allocation of funds in the European Community. This article examines the problem of measuring poverty in rich countries and its relation to social policy, taking for this purpose a case study of France, the United Kingdom and West Germany. It demonstrates the importance of issues which may not be immediately apparent such as whether one considers households or individuals, and the choice of equivalence scale. The authors caution that reliable com- parisons cannot be made of the three countries in the present state statistical knowledge, and go on to argue that the findings need to interpreted in the light of differing social policies.La comparaison de la pauvreté dans différents pays européens joue un rôle important dans le débat politique, les différences de niveau pouvant servir à évaluer la capacité des politiques à lutter contre la pauvreté et à identifier les priorités dans l'allocation de fonds. Procéder à une telle comparaison nécessite un examen attentif des concepts sous-jacents à l'analyse statistique. Cet article discute plusieurs points méthodologiques déterminants : le choix des sources statistiques, le choix d'un indicateur de pauvreté et de ses caractéristiques, l'unité d'analyse employée, le choix d'une échelle d'équivalence et la détermination d'une ligne de pauvreté. Une sélection d'études nationales sur la pauvreté en France, en RFA et au Royaume-Uni permet de montrer comment les choix effectués affectent les conclusions tirées, tant sur l'étendue que sur la composition des populations pauvres. Les aspects conceptuels des études sur la pauvreté rendent ainsi délicate la comparaison de l'efficacité des politiques sociales de chaque pays. Mais l'existence même de ces politiques affecte également la mesure de la pauvreté, les choix méthodologiques reflétant les choix sociaux : l'utilisation, dans les travaux allemands et anglais, de l'allocation universelle d'assistance comme seuil de pauvreté en constitue un exemple. En France, la mise en place d'une telle aide sociale, le RMI, est plus récente. On peut donc espérer tirer des enseignements des expériences allemande et anglaise.Atkinson Anthony B., Cazes Sandrine, Milano S., Assemat J., Jeandidier B., Teekens R., Zaïdi M.A. Mesures de la pauvreté et politiques sociales : une étude comparative de la France, de la RFA et du Royaume-Uni. In: Observations et diagnostics économiques : revue de l'OFCE, n°33, 1990. pp. 105-130
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