Detection of non-melanoma skin cancer by in vivo fluorescence imaging with fluorocoxib A.

Non-melanoma skin cancer (NMSC) is the most common form of cancer in the US and its incidence is increasing. The current standard of care is visual inspection by physicians and/or dermatologists, followed by skin biopsy and pathologic confirmation. We have investigated the use of in vivo fluorescence imaging using fluorocoxib A as a molecular probe for early detection and assessment of skin tumors in mouse models of NMSC. Fluorocoxib A targets the cyclooxygenase-2 (COX-2) enzyme that is preferentially expressed by inflamed and tumor tissue, and therefore has potential to be an effective broadly active molecular biomarker for cancer detection. We tested the sensitivity of fluorocoxib A in a BCC allograft SCID hairless mouse model using a wide-field fluorescence imaging system. Subcutaneous allografts comprised of 1000 BCC cells were detectable above background. These BCC allograft mice were imaged over time and a linear correlation (R(2) = 0.8) between tumor volume and fluorocoxib A signal levels was observed. We also tested fluorocoxib A in a genetically engineered spontaneous BCC mouse model (Ptch1(+/-) K14-Cre-ER2 p53(fl/fl)), where sequential imaging of the same animals over time demonstrated that early, microscopic lesions (100 μm size) developed into visible macroscopic tumor masses over 11 to 17 days. Overall, for macroscopic tumors, the sensitivity was 88% and the specificity was 100%. For microscopic tumors, the sensitivity was 85% and specificity was 56%. These results demonstrate the potential of fluorocoxib A as an in vivo imaging agent for early detection, margin delineation and guided biopsies of NMSCs

Identification of genes that are essential to restrict genome duplication to once per cell division.

Nuclear genome duplication is normally restricted to once per cell division, but aberrant events that allow excess DNA replication (EDR) promote genomic instability and aneuploidy, both of which are characteristics of cancer development. Here we provide the first comprehensive identification of genes that are essential to restrict genome duplication to once per cell division. An siRNA library of 21,584 human genes was screened for those that prevent EDR in cancer cells with undetectable chromosomal instability. Candidates were validated by testing multiple siRNAs and chemical inhibitors on both TP53+ and TP53- cells to reveal the relevance of this ubiquitous tumor suppressor to preventing EDR, and in the presence of an apoptosis inhibitor to reveal the full extent of EDR. The results revealed 42 genes that prevented either DNA re-replication or unscheduled endoreplication. All of them participate in one or more of eight cell cycle events. Seventeen of them have not been identified previously in this capacity. Remarkably, 14 of the 42 genes have been shown to prevent aneuploidy in mice. Moreover, suppressing a gene that prevents EDR increased the ability of the chemotherapeutic drug Paclitaxel to induce EDR, suggesting new opportunities for synthetic lethalities in the treatment of human cancers

Current Distribution in the Three-Dimensional Random Resistor Network at the Percolation Threshold

We study the multifractal properties of the current distribution of the three-dimensional random resistor network at the percolation threshold. For lattices ranging in size from $8^3$ to $80^3$ we measure the second, fourth and sixth moments of the current distribution, finding {\it e.g.\/} that $t/\nu=2.282(5)$ where $t$ is the conductivity exponent and $\nu$ is the correlation length exponent.Comment: 10 pages, latex, 8 figures in separate uuencoded fil

Sinter formation during directed energy deposition of titanium alloy powders

During directed energy deposition (DED) additive manufacturing, powder agglomeration and sintering can occur outside of the melt pool when using titanium alloy powders. Using in situ synchrotron radiography we investigate the mechanisms by which sintering of Ti6242 powder occurs around the pool, performing a parametric study to determine the influence of laser power and stage traverse speed on sinter build-up. The results reveal that detrimental sinter can be reduced using a high laser power or increased stage traverse speed, although the latter also reduces deposition layer thickness. The mechanism of sinter formation during DED was determined to be in-flight heating of the powder particles in the laser beam. Calculations of particle heating under the processing conditions explored in this study confirm that powder particles can reasonably exceed 700 °C, the threshold for Ti surface oxide dissolution, and thus the powder is prone to sintering if not incorporated into the melt pool. The build-up of sinter powder layer on deposit surfaces led to lack of fusion pores. To mitigate sinter formation and its detrimental effects on DED component quality, it is essential that the powder delivery spot area is smaller than the melt pool, ensuring most powder lands in the melt pool

Dietary garlic and hip osteoarthritis: evidence of a protective effect and putative mechanism of action

Background Patterns of food intake and prevalent osteoarthritis of the hand, hip, and knee were studied using the twin design to limit the effect of confounding factors. Compounds found in associated food groups were further studied in vitro. Methods Cross-sectional study conducted in a large population-based volunteer cohort of twins. Food intake was evaluated using the Food Frequency Questionnaire; OA was determined using plain radiographs. Analyses were adjusted for age, BMI and physical activity. Subsequent in vitro studies examined the effects of allium-derived compounds on the expression of matrix-degrading proteases in SW1353 chondrosarcoma cells. Results Data were available, depending on phenotype, for 654-1082 of 1086 female twins (median age 58.9 years; range 46-77). Trends in dietary analysis revealed a specific pattern of dietary intake, that high in fruit and vegetables, showed an inverse association with hip OA (p = 0.022). Consumption of 'non-citrus fruit' (p = 0.015) and 'alliums' (p = 0.029) had the strongest protective effect. Alliums contain diallyl disulphide which was shown to abrogate cytokine-induced matrix metalloproteinase expression. Conclusions Studies of diet are notorious for their confounding by lifestyle effects. While taking account of BMI, the data show an independent effect of a diet high in fruit and vegetables, suggesting it to be protective against radiographic hip OA. Furthermore, diallyl disulphide, a compound found in garlic and other alliums, represses the expression of matrix-degrading proteases in chondrocyte-like cells, providing a potential mechanism of action

The Diverse Properties of the Most Ultraviolet Luminous Galaxies Discovered by the Galaxy Evolution Explorer

We report on the properties of a sample of ultraviolet luminous galaxies (UVLGs) selected by matching the Galaxy Evolution Explorer (GALEX) Surveys with the Sloan Digital Sky Survey Third Data Release. Out of 25362 galaxies between 0.02x10^10 L_solar at 1530 Angstroms (observed wavelength). The properties of this population are well correlated with ultraviolet surface brightness. We find that the galaxies with low UV surface brightness are primarily large spiral systems with a mixture of old and young stellar populations, while the high surface brightness galaxies consist primarily of compact starburst systems. In terms of the behavior of surface brightness with luminosity, size with luminosity, the mass-metallicity relation, and other parameters, the compact UVLGs clearly depart from the trends established by the full sample of galaxies. The subset of compact UVLGs with the highest surface brightness (``supercompact UVLGs'') have characteristics that are remarkably similar to Lyman Break Galaxies at higher redshift. They are much more luminous than typical local ultraviolet-bright starburst galaxies and blue compact dwarf galaxies. They have metallicities that are systematically lower than normal galaxies of the same stellar mass, indicating that they are less chemically evolved. In all these respects, they are the best local analogs for Lyman Break Galaxies.Comment: Fixed error in ObjID column of Table 1. 30 pages, 12 figures. Accepted for the GALEX special issue of ApJS. Abstract abridge

GALEX Ultraviolet Photometry of Globular Clusters in M31

We present ultraviolet photometry for globular clusters (GCs) in M31 from 15 square deg of imaging using the Galaxy Evolution Explorer (GALEX). We detect 200 and 94 GCs with certainty in the near-ultraviolet (NUV; 1750 - 2750 Angstroms) and far-ultraviolet (FUV; 1350 - 1750 Angstroms) bandpasses, respectively. Our rate of detection is about 50% in the NUV and 23% in the FUV, to an approximate limiting V magnitude of 19. Out of six clusters with [Fe/H]>-1 seen in the NUV, none is detected in the FUV bandpass. Furthermore, we find no candidate metal-rich clusters with significant FUV flux, because of the contribution of blue horizontal-branch (HB) stars, such as NGC 6388 and NGC 6441, which are metal-rich Galactic GCs with hot HB stars. We show that our GALEX photometry follows the general color trends established in previous UV studies of GCs in M31 and the Galaxy. Comparing our data with Galactic GCs in the UV and with population synthesis models, we suggest that the age range of M31 and Galactic halo GCs are similar.Comment: This paper will be published as part of the Galaxy Evolution Explorer (GALEX) Astrophysical Journal Letters Special Issue. Links to the full set of papers will be available at http://www.galex.caltech.edu/PUBLICATIONS/ after November 22, 200

Recent star formation in nearby galaxies from GALEX imaging:M101 and M51

The GALEX (Galaxy Evolution Explorer) Nearby Galaxies Survey is providing deep far-UV and near-UV imaging for a representative sample of galaxies in the local universe. We present early results for M51 and M101, from GALEX UV imaging and SDSS optical data in five bands. The multi-band photometry of compact stellar complexes in M101 is compared to population synthesis models, to derive ages, reddening, reddening-corrected luminosities and current/initial masses. The GALEX UV photometry provides a complete census of young compact complexes on a approximately 160pc scale. A galactocentric gradient of the far-UV - near-UV color indicates younger stellar populations towards the outer parts of the galaxy disks, the effect being more pronounced in M101 than in M51.Comment: This paper will be published as part of the Galaxy Evolution Explorer (GALEX) Astrophysical Journal Letters Special Issue. Full paper available from http://dolomiti.pha.jhu.edu . Links to full set of papers will be available at http://www.galex.caltech.edu/PUBLICATIONS/ after November 22, 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