Differential chemosensitivity to antifolate drugs between RAS and BRAF melanoma cells.

BACKGROUND: The importance of the genetic background of cancer cells for the individual susceptibility to cancer treatments is increasingly apparent. In melanoma, the existence of a BRAF mutation is a main predictor for successful BRAF-targeted therapy. However, despite initial successes with these therapies, patients relapse within a year and have to move on to other therapies. Moreover, patients harbouring a wild type BRAF gene (including 25% with NRAS mutations) still require alternative treatment such as chemotherapy. Multiple genetic parameters have been associated with response to chemotherapy, but despite their high frequency in melanoma nothing is known about the impact of BRAF or NRAS mutations on the response to chemotherapeutic agents. METHODS: Using cell proliferation and DNA methylation assays, FACS analysis and quantitative-RT-PCR we have characterised the response of a panel of NRAS and BRAF mutant melanoma cell lines to various chemotherapy drugs, amongst them dacarbazine (DTIC) and temozolomide (TMZ) and DNA synthesis inhibitors. RESULTS: Although both, DTIC and TMZ act as alkylating agents through the same intermediate, NRAS and BRAF mutant cells responded differentially only to DTIC. Further analysis revealed that the growth-inhibitory effects mediated by DTIC were rather due to interference with nucleotide salvaging, and that NRAS mutant melanoma cells exhibit higher activity of the nucleotide synthesis enzymes IMPDH and TK1. Importantly, the enhanced ability of RAS mutant cells to use nucleotide salvaging resulted in resistance to DHFR inhibitors. CONCLUSION: In summary, our data suggest that the genetic background in melanoma cells influences the response to inhibitors blocking de novo DNA synthesis, and that defining the RAS mutation status could be used to stratify patients for the use of antifolate drugs

A preliminary evaluation of a new control-knob design for electronic equipment

Two experiments were carried out using five subjects to compare performance using standard and flush fitting rotary controls for electronic equipment. It vas found that the flush knob could be rotated more quickly through several revolutions, but a given setting accuracy was achieved less quickly using this flush knob. Some of the more general advantages and disadvantages of the flush knob are outlined. It should be noted that the primary objective of this study was to provide the participants with some experience in carrying out Human Factors studies and the time allowed was not such as to permit a comprehensive evaluation of the new knob design

An appraisal of the sciaky 300 KVA projection/spot welding equipment

Using the Systems Design Procedure developed at Cranfield, an appraisal of the Sciaky Welding Equipment has been carried out. In particular, the interface on the electronic control cabinet has been redesigned, five solutions of varying engineering complexity and cost being presented

The Dust Content of Galaxy Clusters

We report on the detection of reddening toward z ~ 0.2 galaxy clusters. This is measured by correlating the Sloan Digital Sky Survey cluster and quasar catalogs and by comparing the photometric and spectroscopic properties of quasars behind the clusters to those in the field. We find mean E(B-V) values of a few times 10^-3 mag for sight lines passing ~Mpc from the clusters' center. The reddening curve is typical of dust but cannot be used to distinguish between different dust types. The radial dependence of the extinction is shallow near the cluster center suggesting that most of the detected dust lies at the outskirts of the clusters. Gravitational magnification of background z ~ 1.7 sources seen on Mpc (projected) scales around the clusters is found to be of order a few per cent, in qualitative agreement with theoretical predictions. Contamination by different spectral properties of the lensed quasar population is unlikely but cannot be excluded.Comment: 4 pages, 3 figure

Measurements of Far-UV Emission from Elliptical Galaxies at z=0.375

The ``UV upturn'' is a sharp rise in spectra of elliptical galaxies shortward of rest-frame 2500 A. It is a ubiquitous phenomenon in nearby giant elliptical galaxies, and is thought to arise primarily from low-mass evolved stars on the extreme horizontal branch and beyond. Models suggest that the UV upturn is a very strong function of age for these old stellar populations, increasing as the galaxy gets older. In some models the change in UV/optical flux ratio is a factor of 25 over timescales of less than 3 Gyr. To test the predictions for rapid evolution of the UV upturn, we have observed a sample of normal elliptical galaxies in the z=0.375 cluster Abell 370 with the Faint Object Camera aboard the Hubble Space Telescope. A combination of two long-pass filters was used to isolate wavelengths shortward of rest-frame 2700 A, providing a measurement of the UV upturn at a lookback time of approximately 4 Gyr. Surprisingly, the four elliptical galaxies observed show a range of UV upturn strength that is similar to that seen in nearby elliptical galaxies, with an equivalent 1550-V color ranging from 2.9-3.4 mag. Our result is inconsistent with some models for the UV upturn; other models are consistent only for a high redshift of formation (z_f >= 4).Comment: 4 pages, Latex. 1 figure. To appear in ApJL. Uses emulateapj.sty and apjfonts.sty. Revision includes minor ApJ edits & fixes typo

The Luminosity Function of Galaxies in Compact Groups

From R-band images of 39 Hickson compact groups (HCGs), we use galaxy counts to determine a luminosity function extending to M_R=-14.0, approximately two magnitudes deeper than previous compact group luminosity functions. We find that a single Schechter function is a poor fit to the data, so we fit a composite function consisting of separate Schechter functions for the bright and faint galaxies. The bright end is best fit with M^*=-21.6 and alpha=-0.52 and the faint end with M^*=-16.1 and alpha=-1.17. The decreasing bright end slope implies a deficit of intermediate luminosity galaxies in our sample of HCGs and the faint end slope is slightly steeper than that reported for earlier HCG luminosity functions. Furthermore, luminosity functions of subsets of our sample reveal more substantial dwarf populations for groups with x-ray halos, groups with tidal dwarf candidates, and groups with a dominant elliptical or lenticular galaxy. Collectively, these results support the hypothesis that within compact groups, the initial dwarf galaxy population is replenished by "subsequent generations" formed in the tidal debris of giant galaxy interactions.Comment: 26 pages, to be published in The Astrophysical Journal, 8 greyscale plates (figures 1 and 2) can be retrieved at http://www.astro.psu.edu/users/sdh/pubs.htm

Morphology and evolution of emission line galaxies in the Hubble Ultra Deep Field

We investigate the properties and evolution of a sample of galaxies selected to have prominent emission lines in low-resolution grism spectra of the Hubble Ultra Deep Field (HUDF). These objects, eGRAPES, are late type blue galaxies, characterized by small proper sizes (R_50 < 2 kpc) in the 4350A rest-frame, low masses (5x10^9 M_sun), and a wide range of luminosities and surface brightnesses. The masses, sizes and volume densities of these objects appear to change very little up to a redshift of z=1.5. On the other hand, their surface brightness decreases significantly from z=1.5 to z=0 while their mass-to-light ratio increases two-folds. This could be a sign that most of low redshift eGRAPES have an older stellar population than high redshift eGRAPES and hence that most eGRAPES formed at higher redshifts. The average volume density of eGRAPES is (1.8 \pm 0.3)x10^{-3} Mpc^{-3} between 0.3 < z < 1.5. Many eGRAPES would formally have been classified as Luminous Compact Blue Galaxies (LCBGs) if these had been selected based on small physical size, blue intrinsic color, and high surface brightness, while the remainder of the sample discussed in this paper forms an extension of LCBGs towards fainter luminosities.Comment: Accepted, to appear in Ap

Far-ultraviolet imaging of the Hubble Deep Field-North: Star formation in normal galaxies at z < 1

We present far-ultraviolet (FUV) imaging of the Hubble Deep Field-North (HDF-N) taken with the Solar Blind Channel of the Advanced Camera for Surveys (ACS SBC) and the FUV MAMA detector of the Space Telescope Imaging Spectrograph onboard the Hubble Space Telescope. The full WFPC2 deep field has been observed at 1600 Å. We detect 134 galaxies and one star down to a limit of FUV_(AB) ~ 29. All sources have counterparts in the WFPC2 image. Redshifts (spectroscopic or photometric) for the detected sources are in the range 0 < z < 1. We find that the FUV galaxy number counts are higher than those reported by GALEX, which we attribute at least in part to cosmic variance in the small HDF-N field of view. Six of the 13 Chandra sources at z < 0.85 in the HDF-N are detected in the FUV, and those are consistent with starbursts rather than active galactic nuclei. Cross-correlating with Spitzer sources in the field, we find that the FUV detections show general agreement with the expected L_(IR)/L_(UV) versus β relationship. We infer star formation rates (SFRs), corrected for extinction using the UV slope, and find a median value of 0.3 M_☉ yr^(-1) for FUV-detected galaxies, with 75% of detected sources having SFR < 1 M_☉ yr^(-1). Examining the morphological distribution of sources, we find that about half of all FUV-detected sources are identified as spiral galaxies. Half of morphologically selected spheroid galaxies at z < 0.85 are detected in the FUV, suggesting that such sources have had significant ongoing star formation in the epoch since z ~ 1

Dynamical Friction in dE Globular Cluster Systems

The dynamical friction timescale for globular clusters to sink to the center of a dwarf elliptical galaxy (dE) is significantly less than a Hubble time if the halos have King-model or isothermal profiles and the globular clusters formed with the same radial density profile as the underlying stellar population. We examine the summed radial distribution of the entire globular cluster systems and the bright globular cluster candidates in 51 Virgo and Fornax Cluster dEs for evidence of dynamical friction processes. We find that the summed distribution of the entire globular cluster population closely follows the exponential profile of the underlying stellar population. However, there is a deficit of bright clusters within the central regions of dEs (excluding the nuclei), perhaps due to the orbital decay of these massive clusters into the dE cores. We also predict the magnitude of each dE's nucleus assuming the nuclei form via dynamical friction. The observed trend of decreasing nuclear luminosity with decreasing dE luminosity is much stronger than predicted if the nuclei formed via simple dynamical friction processes. We find that the bright dE nuclei could have been formed from the merger of orbitally decayed massive clusters, but the faint nuclei are several magnitudes fainter than expected. These faint nuclei are found primarily in M_V > -14 dEs which have high globular cluster specific frequencies and extended globular cluster systems. In these galaxies, supernovae-driven winds, high central dark matter densities, extended dark matter halos, the formation of new star clusters, or tidal interactions may act to prevent dynamical friction from collapsing the entire globular cluster population into a single bright nucleus.Comment: 15 pages, 2 tables, 7 figures; to appear in the Astrophysical Journal, April 20, 200