819 research outputs found

    An Examination of the Financial Health of Georgia's Start-Up Charter Schools - Brief

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    This report examines the financial health of start-up charter schools in Georgia during the 2006-07 school year. FRC Brief 19

    Photometry of Proxima Centauri and Barnard's Star Using HST Fine Guidance Sensor 3: A Search for Periodic Variations

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    We have observed Proxima Centauri and Barnard's Star with Hubble Space Telescope Fine Guidance Sensor 3. Proxima Centauri exhibits small-amplitude, periodic photometric variations. Once several sources of systematic photometric error are corrected, we obtain 2 milli-magnitude internal photometric precision. We identify two distinct behavior modes over the past four years: higher amplitude, longer period; smaller amplitude, shorter period. Within the errors one period (P ~ 83d) is twice the other. Barnard's Star shows very weak evidence for periodicity on a timescale of approximately 130 days. If we interpret these periodic phenomena as rotational modulation of star spots, we identify three discrete spots on Proxima Cen and possibly one spot on Barnard's Star. We find that the disturbances change significantly on time scales as short as one rotation period.Comment: 39 pages, 17 figure

    Interferometric Astrometry of Proxima Centauri and Barnard's Star Using Hubble Space Telescope Fine Guidance Sensor 3: Detection Limits for sub-Stellar Companions

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    We report on a sub-stellar companion search utilizing interferometric fringe-tracking astrometry acquired with Fine Guidance Sensor 3 (FGS 3) on the Hubble Space Telescope. Our targets were Proxima Centauri and Barnard's Star. We obtain absolute parallax values for Proxima Cen pi_{abs} = 0.7687 arcsecond and for Barnard's Star pi_{abs} = 0.5454 arcsecond. Once low-amplitude instrumental systematic errors are identified and removed, our companion detection sensitivity is less than or equal to one Jupiter mass for periods longer than 60 days for Proxima Cen. Between the astrometry and the radial velocity results we exclude all companions with M > 0.8M_{Jup} for the range of periods 1 < P < 1000 days. For Barnard's Star our companion detection sensitivity is less than or equal to one Jupiter mass for periods long er than 150 days. Our null results for Barnard's Star are consistent with those of Gatewood (1995).Comment: 35 pages, 13 figures, to appear in August 1999 A

    Astrometry with Hubble Space Telescope: A Parallax of the Fundamental Distance Calibrator RR Lyrae

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    We present an absolute parallax and relative proper motion for the fundamental distance scale calibrator, RR Lyr. We obtain these with astrometric data from FGS 3, a white-light interferometer on HST. We find πabs=3.82±0.2\pi_{abs} = 3.82 \pm 0.2 mas. Spectral classifications and VRIJHKT2_2M and DDO51 photometry of the astrometric reference frame surrounding RR Lyr indicate that field extinction is low along this line of sight. We estimate =0.07\pm0.03 for these reference stars. The extinction suffered by RR Lyr becomes one of the dominant contributors to the uncertainty in its absolute magnitude. Adopting the average field absorption, =0.07 \pm 0.03, we obtain M_V^{RR} = 0.61 ^{-0.11}_{+0.10}. This provides a distance modulus for the LMC, m-M = 18.38 - 18.53^{-0.11}_{+0.10} with the average extinction-corrected magnitude of RR Lyr variables in the LMC, , remaining a significant uncertainty. We compare this result to more than 80 other determinations of the distance modulus of the LMC.Comment: Several typos corrected. To appear in The Astronomical Journal, January 200

    Genetic variation at MECOM, TERT, JAK2 and HBS1L-MYB predisposes to myeloproliferative neoplasms

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    Clonal proliferation in myeloproliferative neoplasms (MPN) is driven by somatic mutations in JAK2, CALR or MPL, but the contribution of inherited factors is poorly characterized. Using a three-stage genome-wide association study of 3,437 MPN cases and 10,083 controls, we identify two SNPs with genome-wide significance in JAK2V617F-negative MPN: rs12339666 (JAK2; meta-analysis P=1.27 × 10−10) and rs2201862 (MECOM; meta-analysis P=1.96 × 10−9). Two additional SNPs, rs2736100 (TERT) and rs9376092 (HBS1L/MYB), achieve genome-wide significance when including JAK2V617F-positive cases. rs9376092 has a stronger effect in JAK2V617F-negative cases with CALR and/or MPL mutations (Breslow–Day P=4.5 × 10−7), whereas in JAK2V617F-positive cases rs9376092 associates with essential thrombocythemia (ET) rather than polycythemia vera (allelic χ2 P=7.3 × 10−7). Reduced MYB expression, previously linked to development of an ET-like disease in model systems, associates with rs9376092 in normal myeloid cells. These findings demonstrate that multiple germline variants predispose to MPN and link constitutional differences in MYB expression to disease phenotype

    The SF3B1 inhibitor spliceostatin A (SSA) elicits apoptosis in chronic lymphocytic leukemia cells through downregulation of Mcl-1

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    The pro-survival Bcl-2 family member Mcl-1 is expressed in chronic lymphocytic leukemia (CLL), with high expression correlated with progressive disease. The spliceosome inhibitor spliceostatin A (SSA), is known to regulate Mcl-1 and so here we assessed the ability of SSA to elicit apoptosis in CLL. SSA induced apoptosis of CLL cells at low nanomolar concentrations in a dose- and time-dependent manner, but independently of SF3B1 mutational status, IGHV status and CD38 or ZAP70 expression. However, normal B and T cells were less sensitive than CLL cells (P=0.006 and P&lt;0.001, respectively). SSA altered the splicing of anti-apoptotic MCL-1L to MCL-1s in CLL cells coincident with induction of apoptosis. Overexpression studies in Ramos cells suggested Mcl-1 was important for SSA-induced killing since its expression inversely correlated with apoptosis (P=0.001). IL4 and CD40L, present in patient lymph nodes, are known to protect tumor cells from apoptosis and significantly inhibited SSA, ABT-263 and ABT-199 induced killing following administration to CLL cells (P=0.008). However, by combining SSA with the Bcl-2/Bcl-xL antagonists ABT-263 or ABT-199, we were able to overcome this pro-survival effect. We conclude that SSA combined with Bcl-2/Bcl-xL antagonists may have therapeutic utility for CL
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