Pancreas Cancer Survival in the Gemcitabine Era

After multiple positive studies, gemcitabine, approved for the treatment of pancreas cancer by the FDA in 1977, became standard of care. Whether this therapeutic advance has translated into longer survival for pancreas cancer patients in general has not been established. This study, derived from SEER (Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute) data, compared the survival experiences of the gemcitabine (1998–2004) and pre-gemcitabine (1988–1997) eras for 7,151 patients who had metastatic disease and did not undergo extirpative surgery, 14,369 patients who had not undergone surgery and had metastases, 5,042 patients who had undergone surgery and did not have metastases, and 5,011 patients who had undergone surgery and had metastases. Calculated survival time ratios (TR) were adjusted for radiotherapy history, grade, nodal status, loco-regional extent of disease, age, race, and gender. For those who did not undergo extirpative surgery, improvements in survival in the gemcitabine era (1998–2004) versus the prior time period (1988–1997) seen for patients with metastatic cancer (TR = 1.20, 95% c.i. 1.15–1.25) were not seen for those without metastatic cancer (TR = 1.05, 95% c.i. 1.00–1.15). For those who did undergo extirpative surgery, improvements were much more dramatic for those with metastatic cancer (TR = 1.61, 95% c.i. 1.45–1.80) than those without metastases (TR = 1.23, 95% c.i. 1.15–1.31). The results are consistent with the notion that the promising findings with respect to gemcitabine in the controlled clinical trials have found expression in the general population of patients with pancreas cancer

Genotoxic responses to titanium dioxide nanoparticles and fullerene in gpt delta transgenic MEF cells

Background: Titanium dioxide (TiO2) nanoparticles and fullerene (C60) are two attractive manufactured nanoparticles with great promise in industrial and medical applications. However, little is known about the genotoxic response of TiO2 nanoparticles and C60 in mammalian cells. In the present study, we determined the mutation fractions induced by either TiO2 nanoparticles or C60 in gpt delta transgenic mouse primary embryo fibroblasts (MEF) and identified peroxynitrite anions (ONOO-) as an essential mediator involved in such process. Results: Both TiO2 nanoparticles and C60 dramatically increased the mutation yield, which could be abrogated by concurrent treatment with the endocytosis inhibitor, Nystatin. Under confocal scanning microscopy together with the radical probe dihydrorhodamine 123 (DHR 123), we found that there was a dose-dependent formation of ONOO- in live MEF cells exposed to either TiO2 nanoparticles or C60, and the protective effects of antioxidants were demonstrated by the nitric oxide synthase (NOS) inhibitor, NG-methyl-L-arginine (L-NMMA). Furthermore, suppression of cyclooxygenase-2 (COX-2) activity by using the chemical inhibitor NS-398 significantly reduced mutation frequency of both TiO2 nanoparticles and C60. Conclusion: Our results provided novel information that both TiO2 nanoparticles and C60 were taken up by cells and induced kilo-base pair deletion mutations in a transgenic mouse mutation system. The induction of ONOO- may be a critical signaling event for nanoparticle genotoxicity

Winter weather and lake-watershed physical configuration drive phosphorus, iron, and manganese dynamics in water and sediment of ice-covered lakes

While decreasing occurrence and duration of lake ice cover is well-documented, biogeochemical dynamics in frozen lakes remain poorly understood. Here, we interpret winter physical and biogeochemical time series from eutrophic Missisquoi Bay (MB) and hyper-eutrophic Shelburne Pond (SP) to describe variable drivers of under ice biogeochemistry in systems of fundamentally different lake-watershed physical configurations (lake area, lake : watershed area). The continuous cold of the 2015 winter drove the MB sediment-water interface to the most severe and persistent suboxic state ever documented at this site, promoting the depletion of redox-sensitive phases in sediments, and an expanding zone of bottom water enriched in reactive species of Mn, Fe, and P. In this context, lake sediment and water column inventories of reactive chemical species were sensitive to the severity and persistence of subfreezing temperatures. During thaws, event provenance and severity impact lake thermal structure and mixing, water column enrichment in P and Fe, and thaw capability to suppress redox front position and internal chemical loading. Nearly identical winter weather manifest differently in nearby SP, where the small surface and watershed areas promoted a warmer, less stratified water column and active phytoplankton populations, impacting biogeochemical dynamics. In SP, Fe and P behavior under ice were decoupled due to active biological cycling, and thaw impacts were different in distribution and composition due to SP's physical structure and related antecedent conditions. We find that under ice biogeochemistry is highly dynamic in both time and space and sensitive to a variety of drivers impacted by climate change

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

Clustering Properties of restframe UV selected galaxies II: Migration of Star Formation sites with cosmic time from GALEX and CFHTLS

We analyze the clustering properties of ultraviolet selected galaxies by using GALEX-SDSS data at z<0.6 and CFHTLS deep u' imaging at z=1. These datasets provide a unique basis at z< 1 which can be directly compared with high redshift samples built with similar selection criteria. We discuss the dependence of the correlation function parameters (r0, delta) on the ultraviolet luminosity as well as the linear bias evolution. We find that the bias parameter shows a gradual decline from high (b > 2) to low redshift (b ~ 0.79^{+0.1}_{-0.08}). When accounting for the fraction of the star formation activity enclosed in the different samples, our results suggest that the bulk of star formation migrated from high mass dark matter halos at z>2 (10^12 < M_min < 10^13 M_sun, located in high density regions), to less massive halos at low redshift (M_min < 10^12 M_sun, located in low density regions). This result extends the ``downsizing'' picture (shift of the star formation activity from high stellar mass systems at high z to low stellar mass at low z) to the dark matter distribution.Comment: Accepted for Publication in the Special GALEX Ap. J. Supplement, December 2007 Version with full resolution fig1 available at http://taltos.pha.jhu.edu/~sebastien/papers/Galex_p2.ps.g

IR and UV Galaxies at z=0.6 -- Evolution of Dust Attenuation and Stellar Mass as Revealed by SWIRE and GALEX

We study dust attenuation and stellar mass of $\rm z\sim 0.6$ star-forming galaxies using new SWIRE observations in IR and GALEX observations in UV. Two samples are selected from the SWIRE and GALEX source catalogs in the SWIRE/GALEX field ELAIS-N1-00 ($\Omega = 0.8$ deg$^2$). The UV selected sample has 600 galaxies with photometric redshift (hereafter photo-z) $0.5 \leq z \leq 0.7$ and NUV$\leq 23.5$ (corresponding to \rm L_{FUV} \geq 10^{9.6} L_\sun). The IR selected sample contains 430 galaxies with $f_{24\mu m} \geq 0.2$ mJy (\rm L_{dust} \geq 10^{10.8} L_\sun) in the same photo-z range. It is found that the mean $\rm L_{dust}/L_{FUV}$ ratios of the z=0.6 UV galaxies are consistent with that of their z=0 counterparts of the same $\rm L_{FUV}$. For IR galaxies, the mean $\rm L_{dust}/L_{FUV}$ ratios of the z=0.6 LIRGs (\rm L_{dust} \sim 10^{11} L_\sun) are about a factor of 2 lower than local LIRGs, whereas z=0.6 ULIRGs (\rm L_{dust} \sim 10^{12} L_\sun) have the same mean $\rm L_{dust}/L_{FUV}$ ratios as their local counterparts. This is consistent with the hypothesis that the dominant component of LIRG population has changed from large, gas rich spirals at z$>0.5$ to major-mergers at z=0. The stellar mass of z=0.6 UV galaxies of \rm L_{FUV} \leq 10^{10.2} L_\sun is about a factor 2 less than their local counterparts of the same luminosity, indicating growth of these galaxies. The mass of z=0.6 UV lunmous galaxies (UVLGs: \rm L_{FUV} > 10^{10.2} L_\sun) and IR selected galaxies, which are nearly exclusively LIRGs and ULIRGs, is the same as their local counterparts.Comment: 27 pages, 8 figures, to be published in the Astrophysical Journal Supplement series dedicated to GALEX result

UV and FIR selected star-forming galaxies at z=0: differences and overlaps

We study two samples of local galaxies, one is UV (GALEX) selected and the other FIR (IRAS) selected, to address the question whether UV and FIR surveys see the two sides ('bright' and 'dark') of the star formation of the same population of galaxies or two different populations of star forming galaxies. No significant difference between the L$_{tot}$ ($=L_{60}+L_{FUV}$) luminosity functions of the UV and FIR samples is found. Also, after the correction for the `Malmquist bias' (bias for flux limited samples), the FIR-to-UV ratio v.s. L$_{tot}$ relations of the two samples are consistent with each other. In the range of 9 \la \log(L_{tot}/L_\sun) \la 12, both can be approximated by a simple linear relation of \log (L_{60}/L_{FUV})=\log(L_{tot}/L_\sun)-9.66. These are consistent with the hypothesis that the two samples represent the same population of star forming galaxies, and their well documented differences in L$_{tot}$ and in FIR-to-UV ratio are due only to the selection effect. A comparison between the UV luminosity functions shows marginal evidence for a population of faint UV galaxies missing in the FIR selected sample. The contribution from these 'FIR-quiet' galaxies to the overall UV population is insignificant, given that the K-band luminosity functions (i.e. the stellar mass functions) of the two samples do not show any significant difference.Comment: 21 pages, 7 figures. Accepted by Ap

New Insight into Intrachromosomal Deletions Induced by Chrysotile in the gpt delta Transgenic Mutation Assay

BACKGROUND: Genotoxicity is often a prerequisite to the development of malignancy. Considerable evidence has shown that exposure to asbestos fibers results in the generation of chromosomal aberrations and multilocus mutations using various in vitro approaches. However, there is less evidence to demonstrate the contribution of deletions to the mutagenicity of asbestos fibers in vivo. OBJECTIVES: In the present study, we investigated the mutant fractions and the patterns induced by chrysotile fibers in gpt delta transgenic mouse primary embryo fibroblasts (MEFs) and compared the results obtained with hydrogen peroxide (H(2)O(2)) in an attempt to illustrate the role of oxyradicals in fiber mutagenesis. RESULTS: Chrysotile fibers induced a dose-dependent increase in mutation yield at the redBA/gam loci in transgenic MEF cells. The number of λ mutants losing both redBA and gam loci induced by chrysotiles at a dose of 1 μg/cm(2) increased by > 5-fold relative to nontreated controls (p < 0.005). Mutation spectra analyses showed that the ratio of λ mutants losing the redBA/gam region induced by chrysotiles was similar to those induced by equitoxic doses of H(2)O(2). Moreover, treatment with catalase abrogated the accumulation of γ-H2AX, a biomarker of DNA double-strand breaks, induced by chrysotile fibers. CONCLUSIONS: Our results provide novel information on the frequencies and types of mutations induced by asbestos fibers in the gpt delta transgenic mouse mutagenic assay, which shows great promise for evaluating fiber/particle mutagenicity in vivo

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