The Carnegie Hubble Program: The Infrared Leavitt Law in IC 1613

We have observed the dwarf galaxy IC 1613, at multiple epochs in the mid-infrared using Spitzer and contemporaneously in the near-infrared using the new FourStar near-infrared camera on Magellan. We have constructed Cepheid period–luminosity relations in the J, H, K_s, [3.6] and [4.5] bands and have used the run of their apparent distance moduli as a function of wavelength to derive the line-of-sight reddening and distance to IC 1613. Using a nine-band fit, we find E(B − V) = 0.05 ± 0.01 mag and an extinction-corrected distance modulus of μ_0 = 24.29 ± 0.03_(statistical) ± 0.03_(systematic) mag. By comparing our multi-band and [3.6] distance moduli to results from the tip of the red giant branch and red clump distance indicators, we find that metallicity has no measurable effect on Cepheid distances at 3.6 μm in the metallicity range −1.0 ≤ [Fe/H] ≤ 0.2, hence derivations of the Hubble constant at this wavelength require no correction for metallicity

The Great Observatories All-Sky LIRG Survey: Comparison of Ultraviolet and Far-Infrared Properties

The Great Observatories All-sky LIRG Survey (GOALS) consists of a complete sample of 202 Luminous Infrared Galaxies (LIRGs) selected from the IRAS Revised Bright Galaxy Sample (RBGS). The galaxies span the full range of interaction stages, from isolated galaxies to interacting pairs to late stage mergers. We present a comparison of the UV and infrared properties of 135 galaxies in GOALS observed by GALEX and Spitzer. For interacting galaxies with separations greater than the resolution of GALEX and Spitzer (2-6"), we assess the UV and IR properties of each galaxy individually. The contribution of the FUV to the measured SFR ranges from 0.2% to 17.9%, with a median of 2.8% and a mean of 4.0 +/- 0.4%. The specific star formation rate of the GOALS sample is extremely high, with a median value (3.9*10^{-10} yr^{-1}) that is comparable to the highest specific star formation rates seen in the Spitzer Infrared Nearby Galaxies Survey sample. We examine the position of each galaxy on the IR excess-UV slope (IRX-beta) diagram as a function of galaxy properties, including IR luminosity and interaction stage. The LIRGs on average have greater IR excesses than would be expected based on their UV colors if they obeyed the same relations as starbursts with L_IR < 10^{11}L_0 or normal late-type galaxies. The ratio of L_IR to the value one would estimate from the IRXg-beta relation published for lower luminosity starburst galaxies ranges from 0.2 to 68, with a median value of 2.7. A minimum of 19% of the total IR luminosity in the RBGS is produced in LIRGs and ULIRGs with red UV colors (beta > 0). Among resolved interacting systems, 32% contain one galaxy which dominates the IR emission while the companion dominates the UV emission. Only 21% of the resolved systems contain a single galaxy which dominates both wavelengths.Comment: 37 pages, 10 figures, accepted for publication in Ap

Characterization of three new serous epithelial ovarian cancer cell lines

<p>Abstract</p> <p>Background</p> <p>Cell lines constitute a powerful model to study cancer, and here we describe three new epithelial ovarian cancer (EOC) cell lines derived from poorly differentiated serous solid tumors (TOV-1946, and TOV-2223G), as well as the matched ascites for one case (OV-1946).</p> <p>Methods</p> <p>In addition to growth parameters, the cell lines were characterized for anchorage independent growth, migration and invasion potential, ability to form spheroids and xenografts in SCID mice.</p> <p>Results</p> <p>While all cell lines were capable of anchorage independent growth, only the TOV-1946 and OV-1946 cell lines were able to form spheroid and produce tumors. Profiling of keratins, p53 and Her2 protein expression was assessed by immunohistochemistry and western blot analyses. Somatic <it>TP53 </it>mutations were found in all cell lines, with TOV-1946 and OV-1946 harboring the same mutation, and none harbored the commonly observed somatic mutations in <it>BRAF</it>, <it>KRAS </it>or germline BRCA1/2 mutations found to recur in the French Canadian population. Conventional cytogenetics and spectral karyotype (SKY) analyses revealed complex karyotypes often observed in ovarian disease.</p> <p>Conclusion</p> <p>This is the first report of the establishment of matched EOC cell lines derived from both solid tumor and ascites of the same patient.</p

Tracing PAHs and Warm Dust Emission in the Seyfert Galaxy NGC 1068

We present a study of the nearby Seyfert galaxy NGC 1068 using mid- and far- infrared data acquired with the IRAC, IRS, and MIPS instruments aboard the Spitzer Space Telescope. The images show extensive 8 um and 24 um emission coinciding with star formation in the inner spiral approximately 15" (1 kpc) from the nucleus, and a bright complex of star formation 47" (3 kpc) SW of the nucleus. The brightest 8 um PAH emission regions coincide remarkably well with knots observed in an Halpha image. Strong PAH features at 6.2, 7.7, 8.6, and 11.3 um are detected in IRS spectra measured at numerous locations inside, within, and outside the inner spiral. The IRAC colors and IRS spectra of these regions rule out dust heated by the AGN as the primary emission source; the SEDs are dominated by starlight and PAH emission. The equivalent widths and flux ratios of the PAH features in the inner spiral are generally consistent with conditions in a typical spiral galaxy ISM. Interior to the inner spiral, the influence of the AGN on the ISM is evident via PAH flux ratios indicative of a higher ionization parameter and a significantly smaller mean equivalent width than observed in the inner spiral. The brightest 8 and 24 um emission peaks in the disk of the galaxy, even at distances beyond the inner spiral, are located within the ionization cones traced by [O III]/Hbeta, and they are also remarkably well aligned with the axis of the radio jets. Although it is possible that radiation from the AGN may directly enhance PAH excitation or trigger the formation of OB stars that subsequently excite PAH emission at these locations in the inner spiral, the orientation of collimated radiation from the AGN and star formation knots in the inner spiral could be coincidental. (abridged)Comment: 20 pages, 11 figures; AJ, accepted; full resolution version available at http://spider.ipac.caltech.edu/staff/jhhowell/astro/howelln1068.pd

The Spitzer Survey of Stellar Structure in Galaxies (S^4G)

The Spitzer Survey of Stellar Structure in Galaxies S^4G is an Exploration Science Legacy Program approved for the Spitzer post-cryogenic mission. It is a volume-, magnitude-, and size-limited (d < 40 Mpc, |b| > 30 degrees, m_(Bcorr) < 15.5, D25>1') survey of 2,331 galaxies using IRAC at 3.6 and 4.5 microns. Each galaxy is observed for 240 s and mapped to > 1.5 x D25. The final mosaicked images have a typical 1 sigma rms noise level of 0.0072 and 0.0093 MJy / sr at 3.6 and 4.5 microns, respectively. Our azimuthally-averaged surface brightness profile typically traces isophotes at mu_3.6 (AB) (1 sigma) ~ 27 mag arcsec^-2, equivalent to a stellar mass surface density of ~ 1 Msun pc^-2. S^4G thus provides an unprecedented data set for the study of the distribution of mass and stellar structures in the local Universe. This paper introduces the survey, the data analysis pipeline and measurements for a first set of galaxies, observed in both the cryogenic and warm mission phase of Spitzer. For every galaxy we tabulate the galaxy diameter, position angle, axial ratio, inclination at mu_3.6 (AB) = 25.5 and 26.5 mag arcsec^-2 (equivalent to ~ mu_B (AB) =27.2 and 28.2 mag arcsec^-2, respectively). These measurements will form the initial S^4G catalog of galaxy properties. We also measure the total magnitude and the azimuthally-averaged radial profiles of ellipticity, position angle, surface brightness and color. Finally, we deconstruct each galaxy using GALFIT into its main constituent stellar components: the bulge/spheroid, disk, bar, and nuclear point source, where necessary. Together these data products will provide a comprehensive and definitive catalog of stellar structures, mass and properties of galaxies in the nearby Universe.Comment: Accepted for Publication in PASP, 14 pages, 13 figure

BTN3A2 Expression in Epithelial Ovarian Cancer Is Associated with Higher Tumor Infiltrating T Cells and a Better Prognosis

BTN3A2/BT3.2 butyrophilin mRNA expression by tumoral cells was previously identified as a prognostic factor in a small cohort of high grade serous epithelial ovarian cancer (HG-EOC). Here, we evaluated the prognostic value of BT3.2 at the protein level in specimen from 199 HG-EOC patients. As the only known role of butyrophilin proteins is in immune regulation, we evaluated the association between BT3.2 expression and intratumoral infiltration of immune cells by immunohistochemistry with specific antibodies against BT3.2, CD3, CD4, CD8, CD20, CD68 and CD206. Epithelial BT3.2 expression was significantly associated with longer overall survival and lower risk of disease progression (HR = 0.651, p = 0.006 and HR = 0.642, p = 0.002, respectively) and significantly associated with a higher density of infiltrating T cells, particularly CD4+ cells (0.272, p<0.001). We also observed a strong association between the relative density of CD206+ cells, as evaluated by the ratio of intratumoral CD206+/CD68+ expression, and risk of disease progression (HR = 1.355 p = 0.044, respectively). In conclusion, BT3.2 protein is a potential prognostic biomarker for the identification of HG-EOC patients with better outcome. In contrast, high CD206+/CD68+ expression is associated with high risk of disease progression. While the role of BT3.2 is still unknown, our result suggest that BT3.2 expression by epithelial cells may modulates the intratumoral infiltration of immune cells

Role of Pirh2 in Mediating the Regulation of p53 and c-Myc

Ubiquitylation is fundamental for the regulation of the stability and function of p53 and c-Myc. The E3 ligase Pirh2 has been reported to polyubiquitylate p53 and to mediate its proteasomal degradation. Here, using Pirh2 deficient mice, we report that Pirh2 is important for the in vivo regulation of p53 stability in response to DNA damage. We also demonstrate that c-Myc is a novel interacting protein for Pirh2 and that Pirh2 mediates its polyubiquitylation and proteolysis. Pirh2 mutant mice display elevated levels of c-Myc and are predisposed for plasma cell hyperplasia and tumorigenesis. Consistent with the role p53 plays in suppressing c-Myc-induced oncogenesis, its deficiency exacerbates tumorigenesis of Pirh2−/− mice. We also report that low expression of human PIRH2 in lung, ovarian, and breast cancers correlates with decreased patients' survival. Collectively, our data reveal the in vivo roles of Pirh2 in the regulation of p53 and c-Myc stability and support its role as a tumor suppressor

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Tumor intrinsic and extrinsic immune functions of CD155

CD155 (PVR/necl5/Tage4), a member of the nectin-like family of adhesion molecules, is highly upregulated on tumor cells across multiple cancer types and has been associated with worse patient outcomes. In addition to well described cell-intrinsic roles promoting tumor progression and metastasis, CD155 has now been implicated in immune regulation. The role of CD155 as a potent immune ligand with diverse cell-extrinsic functions is now being defined. CD155 signaling to immune cells is mediated through interactions with the co-stimulatory immune receptor CD226 (DNAM-1) and the inhibitory checkpoint receptors TIGIT and CD96, which are differentially regulated at the cell surface on T cells and NK cells. The integration of signals from CD155 cognate receptors modifies the activity of tumor-infiltrating lymphocytes in a context-dependent manner, making CD155 an attractive target for immune-oncology. Preclinical studies suggest that targeting this axis can improve immune-mediated tumor control, particularly when combined with existing anti-PD-1 checkpoint therapies. In this review, we discuss the roles of CD155 on host and tumor cells in controlling tumor progression and discuss the possibility of targeting CD155 for cancer therapy