Chimeric antigen receptors that trigger phagocytosis

Chimeric antigen receptors (CARs) are synthetic receptors that reprogram T cells to kill cancer. The success of CAR-T cell therapies highlights the promise of programmed immunity and suggests that applying CAR strategies to other immune cell lineages may be beneficial. Here, we engineered a family of Chimeric Antigen Receptors for Phagocytosis (CAR-Ps) that direct macrophages to engulf specific targets, including cancer cells. CAR-Ps consist of an extracellular antibody fragment, which can be modified to direct CAR-P activity towards specific antigens. By screening a panel of engulfment receptor intracellular domains, we found that the cytosolic domains from Megf10 and FcRɣ robustly triggered engulfment independently of their native extracellular domain. We show that CAR-Ps drive specific engulfment of antigen-coated synthetic particles and whole human cancer cells. Addition of a tandem PI3K recruitment domain increased cancer cell engulfment. Finally, we show that CAR-P expressing murine macrophages reduce cancer cell number in co-culture by over 40%

The Star Formation and Extinction Co-Evolution of UV-Selected Galaxies over 0.05<z<1.2

We use a new stacking technique to obtain mean mid IR and far IR to far UV flux ratios over the rest near-UV/near-IR color-magnitude diagram. We employ COMBO-17 redshifts and COMBO-17 optical, GALEX far and near UV, Spitzer IRAC and MIPS Mid IR photometry. This technique permits us to probe infrared excess (IRX), the ratio of far IR to far UV luminosity, and specific star formation rate (SSFR) and their co-evolution over two orders of magnitude of stellar mass and redshift 0.1<z<1.2. We find that the SSFR and the characteristic mass (M_0) above which the SSFR drops increase with redshift (downsizing). At any given epoch, IRX is an increasing function of mass up to M_0. Above this mass IRX falls, suggesting gas exhaustion. In a given mass bin below M_0 IRX increases with time in a fashion consistent with enrichment. We interpret these trends using a simple model with a Schmidt-Kennicutt law and extinction that tracks gas density and enrichment. We find that the average IRX and SSFR follows a galaxy age parameter which is determined mainly by the galaxy mass and time since formation. We conclude that blue sequence galaxies have properties which show simple, systematic trends with mass and time such as the steady build-up of heavy elements in the interstellar media of evolving galaxies and the exhaustion of gas in galaxies that are evolving off the blue sequence. The IRX represents a tool for selecting galaxies at various stages of evolution.Comment: Accepted for publication in GALEX Special Ap.J.Suppl., December, 200

Extinction Corrected Star Formation Rates Empirically Derived from Ultraviolet-Optical Colors

Using a sample of galaxies from the Sloan Digital Sky Survey spectroscopic catalog with measured star-formation rates (SFRs) and ultraviolet (UV) photometry from the GALEX Medium Imaging Survey, we derived empirical linear correlations between the SFR to UV luminosity ratio and the UV-optical colors of blue sequence galaxies. The relations provide a simple prescription to correct UV data for dust attenuation that best reconciles the SFRs derived from UV and emission line data. The method breaks down for the red sequence population as well as for very blue galaxies such as the local ``supercompact'' UV luminous galaxies and the majority of high redshift Lyman Break Galaxies which form a low attenuation sequence of their own.Comment: 20 pages, 11 figures, accepted for publication in the ApJS GALEX special issu

Clustering Properties of restframe UV selected galaxies I: the correlation length derived from GALEX data in the local Universe

We present the first measurements of the angular correlation function of galaxies selected in the far (1530 A) and near (2310 A) Ultraviolet from the GALEX survey fields overlapping SDSS DR5 in low galactic extinction regions. The area used covers 120 sqdeg (GALEX - MIS) down to magnitude AB = 22, yielding a total of 100,000 galaxies. The mean correlation length is ~ 3.7 \pm 0.6 Mpc and no significant trend is seen for this value as a function of the limiting apparent magnitude or between the GALEX bands. This estimate is close to that found from samples of blue galaxies in the local universe selected in the visible, and similar to that derived at z ~ 3 for LBGs with similar rest frame selection criteria. This result supports models that predict anti-biasing of star forming galaxies at low redshift, and brings an additional clue to the downsizing of star formation at z<1.Comment: Accepted for publication in GALEX Special ApJs, December 200

The Recent Star Formation in NGC 6822: an Ultraviolet Study

We characterize the star formation in the low-metallicity galaxy NGC 6822 over the past few hundred million years, using GALEX far-UV (FUV, 1344-1786 A) and near-UV (NUV, 1771-2831 A) imaging, and ground-based Ha imaging. From GALEX FUV image, we define 77 star-forming (SF) regions with area >860 pc^2, and surface brightness <=26.8 mag(AB)arcsec^-2, within 0.2deg (1.7kpc) of the center of the galaxy. We estimate the extinction by interstellar dust in each SF region from resolved photometry of the hot stars it contains: E(B-V) ranges from the minimum foreground value of 0.22mag up to 0.66+-0.21mag. The integrated FUV and NUV photometry, compared with stellar population models, yields ages of the SF complexes up to a few hundred Myr, and masses from 2x10^2 Msun to 1.5x10^6 Msun. The derived ages and masses strongly depend on the assumed type of interstellar selective extinction, which we find to vary across the galaxy. The total mass of the FUV-defined SF regions translates into an average star formation rate (SFR) of 1.4x10^-2 Msun/yr over the past 100 Myr, and SFR=1.0x10^-2 Msun/yr in the most recent 10 Myr. The latter is in agreement with the value that we derive from the Ha luminosity, SFR=0.008 Msun/yr. The SFR in the most recent epoch becomes higher if we add the SFR=0.02 Msun/yr inferred from far-IR measurements, which trace star formation still embedded in dust (age <= a few Myr).Comment: Accepted for publication in ApJ, 21 pages, 6 figures, 3 table

Probing the Intermediate-Age Globular Clusters in NGC 5128 from Ultraviolet Observations

We explore the age distribution of the globular cluster (GC) system of the nearby elliptical galaxy NGC 5128 using ultraviolet (UV) photometry from Galaxy Evolution Explorer (GALEX) observations, with UV - optical colors used as the age indicator. Most GCs in NGC 5128 follow the general trends of GCs in M31 and Milky Way in UV - optical color-color diagram, which indicates that the majority of GCs in NGC 5128 are old similar to the age range of old GCs in M31 and Milky Way. A large fraction of spectroscopically identified intermediate-age GC (IAGC) candidates with ~ 3-8 Gyr are not detected in the FUV passband. Considering the nature of intermediate-age populations being faint in the far-UV (FUV) passband, we suggest that many of the spectroscopically identified IAGCs may be truly intermediate in age. This is in contrast to the case of M31 where a large fraction of spectroscopically suggested IAGCs are detected in FUV and therefore may not be genuine IAGCs but rather older GCs with developed blue horizontal branch stars. Our UV photometry strengthens the results previously suggesting the presence of GC and stellar subpopulation with intermediate age in NGC 5128. The existence of IAGCs strongly indicates the occurrence of at least one more major star formation episode after a starburst at high redshift.Comment: 8 pages, 3 figures, accepted for ApJ Lette

Ultraviolet through Infrared Spectral Energy Distributions from 1000 SDSS Galaxies: Dust Attenuation

The meaningful comparison of models of galaxy evolution to observations is critically dependent on the accurate treatment of dust attenuation. To investigate dust absorption and emission in galaxies we have assembled a sample of ~1000 galaxies with ultraviolet (UV) through infrared (IR) photometry from GALEX, SDSS, and Spitzer and optical spectroscopy from SDSS. The ratio of IR to UV emission (IRX) is used to constrain the dust attenuation in galaxies. We use the 4000A break as a robust and useful, although coarse, indicator of star formation history (SFH). We examine the relationship between IRX and the UV spectral slope (a common attenuation indicator at high-redshift) and find little dependence of the scatter on 4000A break strength. We construct average UV through far-IR spectral energy distributions (SEDs) for different ranges of IRX, 4000A break strength, and stellar mass (M_*) to show the variation of the entire SED with these parameters. When binned simultaneously by IRX, 4000A break strength, and M_* these SEDs allow us to determine a low resolution average attenuation curve for different ranges of M_*. The attenuation curves thus derived are consistent with a lambda^{-0.7} attenuation law, and we find no significant variations with M_*. Finally, we show the relationship between IRX and the global stellar mass surface density and gas-phase-metallicity. Among star forming galaxies we find a strong correlation between IRX and stellar mass surface density, even at constant metallicity, a result that is closely linked to the well-known correlation between IRX and star-formation rate.Comment: 12 pages, 8 figures, 2 tables, appearing in the Dec 2007 GALEX special issue of ApJ Supp (29 papers