Inhibition of RNA polymerase II transcription in human cells by synthetic DNA-binding ligands

Sequence-specific DNA-binding small molecules that can permeate human cells potentially could regulate transcription of specific genes. Multiple cellular DNA-binding transcription factors are required by HIV type 1 for RNA synthesis. Two pyrrole-imidazole polyamides were designed to bind DNA sequences immediately adjacent to binding sites for the transcription factors Ets-l, lymphoid-enhancer binding factor 1, and TATA-box binding protein. These synthetic ligands specifically inhibit DNA-binding of each transcription factor and HIV type 1 transcription in cell-free assays. When used in combination, the polyamides inhibit virus replication by >99% in isolated human peripheral blood lymphocytes, with no detectable cell toxicity, The ability of small molecules to target predetermined DNA sequences located within RNA polymerase II promoters suggests a general approach for regulation of gene expression, as well as a mechanism for the inhibition of viral replication

Fine Guidance Sensing for Coronagraphic Observatories

Three options have been developed for Fine Guidance Sensing (FGS) for coronagraphic observatories using a Fine Guidance Camera within a coronagraphic instrument. Coronagraphic observatories require very fine precision pointing in order to image faint objects at very small distances from a target star. The Fine Guidance Camera measures the direction to the target star. The first option, referred to as Spot, was to collect all of the light reflected from a coronagraph occulter onto a focal plane, producing an Airy-type point spread function (PSF). This would allow almost all of the starlight from the central star to be used for centroiding. The second approach, referred to as Punctured Disk, collects the light that bypasses a central obscuration, producing a PSF with a punctured central disk. The final approach, referred to as Lyot, collects light after passing through the occulter at the Lyot stop. The study includes generation of representative images for each option by the science team, followed by an engineering evaluation of a centroiding or a photometric algorithm for each option. After the alignment of the coronagraph to the fine guidance system, a "nulling" point on the FGS focal point is determined by calibration. This alignment is implemented by a fine alignment mechanism that is part of the fine guidance camera selection mirror. If the star images meet the modeling assumptions, and the star "centroid" can be driven to that nulling point, the contrast for the coronagraph will be maximized

Hubble Space Telescope Imaging of the Circumstellar Nebulosity of T Tauri

Short-exposure Planetary Camera images of T Tauri have been obtained using broadband filters spanning the wavelength range 0.55-0.80 μm. The optically visible star lies very close to an arc of reflection nebulosity. The arc's northern arm extends approximately 5" from the star, while its southwestern arm appears brighter and extends only 2". The arc shows an approximate symmetry along an axis toward the west-northwest, the direction of Hind's Nebula and the blueshifted molecular outflow. The morphology of the reflected light is similar to models of scattered light within an illuminated, axisymmetric outflow cavity in a circumbinary envelope, viewed ≈ 45° from the outflow axis. However, our model images do not successfully account for the amount of limb brightening that is seen. No optical counterpart to the infrared companion is seen to a limiting magnitude of V = 19.6, which suggests A_V > 7 mag toward this source. There is no evidence for an optical tertiary, to a limiting ΔV = 5.1 mag fainter than the primary, at the position where such an object has been previously reported

Recognition of the Minor Groove of DNA by Hairpin Polyamides Containing α-Substituted-β-Amino Acids

Incorporation of the flexible amino acid β-alanine (β) into hairpin polyamides composed of N-methylpyrrole (Py) and N-methylimidazole (Im) amino acids is required for binding to DNA sequences longer than seven base pairs with high affinity and sequence selectivity. Pairing the α-substituted-β-amino acids (S)-isoserine (^SIs), (R)-isoserine (^RIs), β-aminoalanine (Aa), and α-fluoro-β-alanine (Fb) side-by-side with β in hairpin polyamides alters DNA binding affinity and selectivity relative to the parent polyamide containing a β/β pairing. Quantitative DNase I footprinting titration studies on a restriction fragment containing the sequences 5‘-TGCNGTA-3‘ (N = A, T, G, and C) show that the polyamide ImPy^SIsImPy-γ-PyPyβImPy-β-Dp (^SIs/β pairing) binds to N = T (K_a = 4.5 × 10^9 M^(-1)) in preference to N = A (K_a = 6.2 × 10^8 M^(-1)). This result stands in contrast to the essentially degenerate binding of the parent ImPyβImPy-γ-PyPyβImPy-β-Dp (β/β pairing) to N = T and N = A, and to the slight preference of ImPyβImPy-γ-PyPy^SIsImPy-β-Dp (β/^SIs pairing) to N = A over N = T. Additionally, this study reveals that incorporation of ^RIs, Aa, and Fb into polyamides significantly reduces binding affinity. Therefore, DNA binding in the minor groove is sensitive to the stereochemistry, steric bulk, and electronics of the substituent at the α-position of β-amino acids in hairpin polyamides containing β/β pairs

Hubble Space Telescope Observations of the Draco Dwarf Spheroidal

We present an F606W-F814W color-magnitude diagram for the Draco dwarf spheroidal galaxy based on Hubble Space Telescope WFPC2 images. The luminosity function is well-sampled to 3 magnitudes below the turn-off. We see no evidence for multiple turnoffs and conclude that, at least over the field of the view of the WFPC2, star formation was primarily single-epoch. If the observed number of blue stragglers is due to extended star formation, then roughly 6% (upper limit) of the stars could be half as old as the bulk of the galaxy. The color difference between the red giant branch and the turnoff is consistent with an old population and is very similar to that observed in the old, metal-poor Galactic globular clusters M68 and M92. Despite its red horizontal branch, Draco appears to be older than M68 and M92 by 1.6 +/- 2.5 Gyrs, lending support to the argument that the ``second parameter'' which governs horizontal branch morphology must be something other than age. Draco's observed luminosity function is very similar to that of M68, and the derived initial mass function is consistent with that of the solar neighborhood.Comment: 16 pages, AASTeX, 9 postscript figures, figures 1 and 2 available at ftp://bb3.jpl.nasa.gov/pub/draco/. Accepted for publication in the Astronomical Journa

Observations and Implications of the Star Formation History of the LMC

We present derivations of star formation histories based on color-magnitude diagrams of three fields in the LMC from HST/WFPC2 observations. A significant component of stars older than 4 Gyr is required to match the observed color-magnitude diagrams. Models with a dispersion-free age-metallicity relation are unable to reproduce the width of the observed main sequence; models with a range of metallicity at a given age provide a much better fit. Such models allow us to construct complete ``population boxes'' for the LMC based entirely on color-magnitude diagrams; remarkably, these qualitatively reproduce the age-metallicity relation observed in LMC clusters. We discuss some of the uncertainties in deriving star formation histories. We find, independently of the models, that the LMC bar field has a larger relative component of older stars than the outer fields. The main implications suggested by this study are: 1) the star formation history of field stars appears to differ from the age distribution of clusters, 2) there is no obvious evidence for bursty star formation, but our ability to measure bursts shorter in duration than $\sim$ 25% of any given age is limited by the statistics of the observed number of stars, 3) there may be some correlation of the star formation rate with the last close passage of the LMC/SMC/Milky Way, but there is no dramatic effect, and 4) the derived star formation history is probably consistent with observed abundances, based on recent chemical evolution models.Comment: Accepted by AJ, 36 pages including 12 figure

WFPC2 Observations of the Cooling Flow Elliptical in Abell 1795

We present WFPC2 images of the core of the cooling flow cD galaxy in Abell 1795. An irregular, asymmetric dust lane extends 7 \h75 kpc in projection to the north-northwest. The dust shares the morphology observed in the H$\alpha$ and excess UV emission. We see both diffuse and knotty blue emission around the dust lane, especially at the ends. The dust and emission features lie on the edge of the radio lobes, suggesting star formation induced by the radio source or the deflection of the radio jets off of pre-existing dust and gas. We measure an apparent R$_V$ significantly less than 3.1, implying that the extinction law is not Galactic in the dust lane, or the presence of line emission which is proportional to the extinction. The dust mass is at least 2$\times10^{5} h_{75}^{-2}$ M\solar\ and is more likely to be 6.5$\times10^{5} h_{75}^{-2}$ M\solar.Comment: 14 pages, LaTeX, Figure 4 included, Postscript Figs. 1-3 available at ftp://astro.nmsu.edu/pub/JASON/A1795/, accepted for publication in ApJ Letter

TrES-2: The First Transiting Planet in the Kepler Field

We announce the discovery of the second transiting hot Jupiter discovered by the Trans-atlantic Exoplanet Survey. The planet, which we dub TrES-2, orbits the nearby star GSC 03549-02811 every 2.47063 days. From high-resolution spectra, we determine that the star has T_eff = 5960 +/- 100 K and log(g) = 4.4 +/- 0.2, implying a spectral type of G0V and a mass of 1.08 +0.11/-0.05 M_sun. High-precision radial-velocity measurements confirm a sinusoidal variation with the period and phase predicted by the photometry, and rule out the presence of line-bisector variations that would indicate that the spectroscopic orbit is spurious. We estimate a planetary mass of 1.28 +0.09/-0.04 M_Jup. We model B, r, R, and I photometric timeseries of the 1.4%-deep transits and find a planetary radius of 1.24 +0.09/-0.06 R_Jup. This planet lies within the field of view of the NASA Kepler mission, ensuring that hundreds of upcoming transits will be monitored with exquisite precision and permitting a host of unprecedented investigations.Comment: Accepted for publication in ApJL. 15 pages, 2 figure

The JWST/NIRCam coronagraph flight occulters

The NIRCam instrument on the James Webb Space Telescope will have a Lyot coronagraph for high contrast imaging of extrasolar planets and circumstellar disks at λ=2 - 5 μm. Half-tone patterns are used to create graded-transmission image plane masks. These are generated using electron beam lithography and reactive ion etching of a metal layer on an antireflection coated sapphire substrate. We report here on the manufacture and evaluation of the flight occulters