Combinatorial small-molecule therapy prevents uropathogenic Escherichia coli catheter-associated urinary tract infections in mice

Catheter-associated urinary tract infections (CAUTIs) constitute the majority of nosocomial urinary tract infections (UTIs) and pose significant clinical challenges. These infections are polymicrobial in nature and are often associated with multidrug-resistant pathogens, including uropathogenic Escherichia coli (UPEC). Urinary catheterization elicits major histological and immunological alterations in the bladder that can favor microbial colonization and dissemination in the urinary tract. We report that these biological perturbations impact UPEC pathogenesis and that bacterial reservoirs established during a previous UPEC infection, in which bacteriuria had resolved, can serve as a nidus for subsequent urinary catheter colonization. Mannosides, small molecule inhibitors of the type 1 pilus adhesin, FimH, provided significant protection against UPEC CAUTI by preventing bacterial invasion and shifting the UPEC niche primarily to the extracellular milieu and on the foreign body. By doing so, mannosides potentiated the action of trimethoprim-sulfamethoxazole in the prevention and treatment of CAUTI. In this study, we provide novel insights into UPEC pathogenesis in the context of urinary catheterization, and demonstrate the efficacy of novel therapies that target critical mechanisms for this infection. Thus, we establish a proof-of-principle for the development of mannosides to prevent and eventually treat these infections in the face of rising antibiotic-resistant uropathogens

The Local Cluster Survey. I. Evidence of Outside-in Quenching in Dense Environments

The goal of the Local Cluster Survey is to look for evidence of environmentally driven quenching among star-forming galaxies in nearby galaxy groups and clusters. Quenching is linked with environment and stellar mass, and much of the current observational evidence comes from the integrated properties of galaxies. However, the relative size of the stellar and star-forming disk is sensitive to environmental processing and can help identify the mechanisms that lead to a large fraction of quenched galaxies in dense environments. Toward this end, we measure the size of the star-forming disks for 224 galaxies in nine groups and clusters (0.02 0.1 M⊙ yr^(−1)) using 24 μm imaging from the Spitzer Space Telescope. We normalize the 24 μm effective radius (R_(24)) by the size of the stellar disk (R d ). We find that star-forming galaxies with higher bulge-to-total ratios (B/T) and galaxies in more dense environments have more centrally concentrated star formation. Comparison with H I mass fractions and NUV − r colors indicates that a galaxy's transition from gas-rich and blue to depleted and red is accompanied by an increase in the central concentration of star formation. We build a simple model to constrain the timescale over which the star-forming disks shrink in the cluster environment. Our results are consistent with a long-timescale (>2 Gyr) mechanism that produces outside-in quenching, such as the removal of the extended gas halo or weak stripping of the cold disk gas

HST-NICMOS Observations of M31's Metal Rich Globular Clusters and Their Surrounding Fields: II. Results

We have obtained HST-NICMOS observations of five of M31's most metal rich globular clusters: G1, G170, G174, G177 & G280. For the two clusters farthest from the nucleus we statistically subtract the field population and estimate metallicities using K-(J-K) color-magnitude diagrams (CMDs). Based on the slopes of their infrared giant branches we estimate [Fe/H]=-1.22+/-0.43 for G1 and -0.15+/-0.37 for G280. We combine our infrared observations of G1 with two epochs of optical HST-WFPC2 V-band data and identify at least one LPV based on color and variability. The location of G1's giant branch in the K-(V-K) CMD is very similar to that of M107, indicating a higher metallicity than our purely infrared CMD: [Fe/H]=-0.9+/-0.2. For the field surrounding G280, we estimate the metallicity to be -1.3 with a spread of 0.5 from the slope and width of the giant branch. Based on the numbers and luminosities of the brightest giants, we conclude that only a small fraction of the stars in this field could be as young as 2 Gyr, while the majority have ages closer to 10 Gyr. The K-band luminosity functions (LFs) of the upper few magnitudes of G1 and G280, as well as for the fields surrounding all clusters, are indistinguishable from the LF measured in the bulge of our Galaxy. This indicates that these clusters are very similar to Galactic clusters, and at least in the surrounding fields observed, there are no significant populations of young luminous stars.Comment: AAS LaTeX v5.0, 17 pages. Submitted to the A

Safety and Efficacy of Ranibizumab in Diabetic Macular Edema (RESOLVE Study*): A 12-month, randomized, controlled, double-masked, multicenter phase II study

The expression of vascular endothelial growth factor (VEGF) is elevated in diabetic macular edema (DME). Ranibizumab binds to and inhibits multiple VEGF variants. We investigated the safety and efficacy of ranibizumab in DME involving the foveal center

Instrumental performance and results from testing of the BLAST-TNG receiver, submillimeter optics, and MKID arrays

Polarized thermal emission from interstellar dust grains can be used to map magnetic fields in star forming molecular clouds and the diffuse interstellar medium (ISM). The Balloon-borne Large Aperture Submillimeter Telescope for Polarimetry (BLASTPol) flew from Antarctica in 2010 and 2012 and produced degree-scale polarization maps of several nearby molecular clouds with arcminute resolution. The success of BLASTPol has motivated a next-generation instrument, BLAST-TNG, which will use more than 3000 linear polarization sensitive microwave kinetic inductance detectors (MKIDs) combined with a 2.5m diameter carbon fiber primary mirror to make diffraction-limited observations at 250, 350, and 500 $\mu$m. With 16 times the mapping speed of BLASTPol, sub-arcminute resolution, and a longer flight time, BLAST-TNG will be able to examine nearby molecular clouds and the diffuse galactic dust polarization spectrum in unprecedented detail. The 250 $\mu$m detector array has been integrated into the new cryogenic receiver, and is undergoing testing to establish the optical and polarization characteristics of the instrument. BLAST-TNG will demonstrate the effectiveness of kilo-pixel MKID arrays for applications in submillimeter astronomy. BLAST-TNG is scheduled to fly from Antarctica in December 2017 for 28 days and will be the first balloon-borne telescope to offer a quarter of the flight for "shared risk" observing by the community.Comment: Presented at SPIE Millimeter, Submillimeter, and Far-Infrared Detectors and Instrumentation for Astronomy VIII, June 29th, 201

The Peculiar Debris Disk of HD 111520 as Resolved by the Gemini Planet Imager

Using the Gemini Planet Imager (GPI), we have resolved the circumstellar debris disk around HD 111520 at a projected range of ~30-100 AU in both total and polarized $H$-band intensity. The disk is seen edge-on at a position angle of ~165$^{\circ}$ along the spine of emission. A slight inclination or asymmetric warping are covariant and alters the interpretation of the observed disk emission. We employ 3 point spread function (PSF) subtraction methods to reduce the stellar glare and instrumental artifacts to confirm that there is a roughly 2:1 brightness asymmetry between the NW and SE extension. This specific feature makes HD 111520 the most extreme examples of asymmetric debris disks observed in scattered light among similar highly inclined systems, such as HD 15115 and HD 106906. We further identify a tentative localized brightness enhancement and scale height enhancement associated with the disk at ~40 AU away from the star on the SE extension. We also find that the fractional polarization rises from 10 to 40% from 0.5" to 0.8" from the star. The combination of large brightness asymmetry and symmetric polarization fraction leads us to believe that an azimuthal dust density variation is causing the observed asymmetry.Comment: 9 pages, 8 Figures, 1 table, Accepted to Ap

Dynamical Mass Measurement of the Young Spectroscopic Binary V343 Normae AaAb Resolved With the Gemini Planet Imager

We present new spatially resolved astrometry and photometry from the Gemini Planet Imager of the inner binary of the young multiple star system V343 Normae, which is a member of the beta Pictoris moving group. V343 Normae comprises a K0 and mid-M star in a ~4.5 year orbit (AaAb) and a wide 10" M5 companion (B). By combining these data with archival astrometry and radial velocities we fit the orbit and measure individual masses for both components of M_Aa = 1.10 +/- 0.10 M_sun and M_Ab = 0.290 +/- 0.018 M_sun. Comparing to theoretical isochrones, we find good agreement for the measured masses and JHK band magnitudes of the two components consistent with the age of the beta Pic moving group. We derive a model-dependent age for the beta Pic moving group of 26 +/- 3 Myr by combining our results for V343 Normae with literature measurements for GJ 3305, which is another group member with resolved binary components and dynamical masses.Comment: 12 pages, 7 figures. Accepted to A

Improving and Assessing Planet Sensitivity of the GPI Exoplanet Survey with a Forward Model Matched Filter

We present a new matched filter algorithm for direct detection of point sources in the immediate vicinity of bright stars. The stellar Point Spread Function (PSF) is first subtracted using a Karhunen-Lo\'eve Image Processing (KLIP) algorithm with Angular and Spectral Differential Imaging (ADI and SDI). The KLIP-induced distortion of the astrophysical signal is included in the matched filter template by computing a forward model of the PSF at every position in the image. To optimize the performance of the algorithm, we conduct extensive planet injection and recovery tests and tune the exoplanet spectra template and KLIP reduction aggressiveness to maximize the Signal-to-Noise Ratio (SNR) of the recovered planets. We show that only two spectral templates are necessary to recover any young Jovian exoplanets with minimal SNR loss. We also developed a complete pipeline for the automated detection of point source candidates, the calculation of Receiver Operating Characteristics (ROC), false positives based contrast curves, and completeness contours. We process in a uniform manner more than 330 datasets from the Gemini Planet Imager Exoplanet Survey (GPIES) and assess GPI typical sensitivity as a function of the star and the hypothetical companion spectral type. This work allows for the first time a comparison of different detection algorithms at a survey scale accounting for both planet completeness and false positive rate. We show that the new forward model matched filter allows the detection of $50\%$ fainter objects than a conventional cross-correlation technique with a Gaussian PSF template for the same false positive rate.Comment: ApJ accepte

GPI spectra of HR 8799 c, d, and e from 1.5 to 2.4μ\mum with KLIP Forward Modeling

We explore KLIP forward modeling spectral extraction on Gemini Planet Imager coronagraphic data of HR 8799, using PyKLIP and show algorithm stability with varying KLIP parameters. We report new and re-reduced spectrophotometry of HR 8799 c, d, and e in H & K bands. We discuss a strategy for choosing optimal KLIP PSF subtraction parameters by injecting simulated sources and recovering them over a range of parameters. The K1/K2 spectra for HR 8799 c and d are similar to previously published results from the same dataset. We also present a K band spectrum of HR 8799 e for the first time and show that our H-band spectra agree well with previously published spectra from the VLT/SPHERE instrument. We show that HR 8799 c and d show significant differences in their H & K spectra, but do not find any conclusive differences between d and e or c and e, likely due to large error bars in the recovered spectrum of e. Compared to M, L, and T-type field brown dwarfs, all three planets are most consistent with mid and late L spectral types. All objects are consistent with low gravity but a lack of standard spectra for low gravity limit the ability to fit the best spectral type. We discuss how dedicated modeling efforts can better fit HR 8799 planets' near-IR flux and discuss how differences between the properties of these planets can be further explored.Comment: Accepted to AJ, 25 pages, 16 Figure