Ras/Raf-1/MAPK pathway mediates response to tamoxifen but not chemotherapy in breast cancer patients

<b>Purpose</b>: The expression and activation of the Ras/Raf-1/mitogen-activated protein kinase (MAPK) pathway plays an important role in the development and progression of cancer, and may influence response to treatments such as tamoxifen and chemotherapy. In this study we investigated whether the expression and activation of the key components of this pathway influenced clinical outcome, to test the hypothesis that activation of the MAPK pathway drives resistance to tamoxifen and chemotherapy in women with breast cancer. <b>Experimental Design</b>: Breast tumors from patients at the Glasgow Royal Infirmary and others treated within the BR9601 trial were analyzed for expression of the three Ras isoforms, total Raf-1, active and inactive forms of Raf-1 [pRaf(ser338) and pRaf(ser259), respectively], MAPK, and phospho-MAPK using an immunohistochemical approach. Analyses were done with respect to disease free-survival and overall survival. <b>Results</b>: Expression and activation of the Ras pathway was associated with loss of benefit from treatment with tamoxifen but not chemotherapy. Overexpression of pRaf(ser338) was associated with shortened disease-free and overall survival time in univariate analyses. Multivariate analysis suggested pRaf(ser338) was independent of known prognostic markers in predicting outcome following tamoxifen treatment (<i>P</i>=0.03). <b>Conclusion</b>: This study suggests that activation of the Ras pathway predicts for poor outcome on tamoxifen but not chemotherapy, and identifies pRaf(ser338) as a potential marker of resistance to estrogen receptor–targeted therapy. In addition, it suggests that expression of pRaf(ser338) could identify patients for whom tamoxifen alone is insufficient adjuvant systemic therapy, but for whom the addition of chemotherapy may be of benefit

A similarity-based approach to perceptual feature validation

Which object properties matter most in human perception may well vary according to sensory modality, an important consideration for the design of multimodal interfaces. In this study, we present a similarity-based method for comparing the perceptual importance of object properties across modalities and show how it can also be used to perceptually validate computational measures of object properties. Similarity measures for a set of three-dimensional (3D) objects varying in shape and texture were gathered from humans in two modalities (vision and touch) and derived from a set of standard 2D and 3D computational measures (image and mesh subtraction, object perimeter, curvature, Gabor jet filter responses, and the Visual Difference Predictor (VDP)). Multidimensional scaling (MDS) was then performed on the similarity data to recover configurations of the stimuli in 2D perceptual/computational spaces. These two dimensions corresponded to the two dimensions of variation in the stimulus set: shape and texture. In the human visual space, shape strongly dominated texture. In the human haptic space, shape and texture were weighted roughly equally. Weights varied considerably across subjects in the haptic experiment, indicating that different strategies were used. Maps derived from shape-dominated computational measures provided good fits to the human visual map. No single computational measure provided a satisfactory fit to the map derived from mean human haptic data, though good fits were found for individual subjects; a combination of measures with individually-adjusted weights may be required to model the human haptic similarity judgments. Our method provides a high-level approach to perceptual validation, which can be applied in both unimodal and multimodal interface design

Correlated X-ray and Optical Variability in Mkn 509

We present results of a 3 year monitoring campaign of the Seyfert 1 galaxy Markarian 509, using X-ray data from the Rossi X-ray Timing Explorer (RXTE) and optical data taken by the SMARTS consortium. Both light curves show significant variations, and are strongly correlated with the optical flux leading the X-ray flux by 15 days. The X-ray power spectrum shows a steep high-frequency slope of -2.0, breaking to a slope of -1.0 at at timescale of 34 days. The lag from optical to X-ray emission is most likely caused by variations in the accretion disk propagating inward.Comment: 13 pages, 3 figures. Accepted for publication in the Astrophysical Journa

Evaluation of a follow-up programme after curative resection for colorectal cancer

Frequent liver imaging can detect liver metastases from colorectal cancer at an asymptomatic stage. © 1999 Cancer Research Campaig

The First Detection of [O IV] from an Ultraluminous X-ray Source with Spitzer. II. Evidence for High Luminosity in Holmberg II ULX

This is the second of two papers examining Spitzer Infrared Spectrograph (IRS) observations of the ultraluminous X-ray source (ULX) in Holmberg II. Here we perform detailed photoionization modeling of the infrared lines. Our analysis suggests that the luminosity and morphology of the [O IV] 25.89 $\mu$m emission line is consistent with photoionization by the soft X-ray and far ultraviolet (FUV) radiation from the accretion disk of the binary system and inconsistent with narrow beaming. We show that the emission nebula is matter-bounded both in the line of sight direction and to the east, and probably radiation-bounded to the west. A bolometric luminosity in excess of 10$^{40}$ erg s$^{-1}$ would be needed to produce the measured [O IV] flux. We use modeling and previously published studies to conclude that shocks likely contribute very little, if at all, to the high-ionization line fluxes observed in the Holmberg II ULX. Additionally, we find that the spectral type of the companion star has a surprisingly strong effect on the predicted strength of the [O IV] emission. This finding could explain the origin of [O IV] in some starburst systems containing black hole binaries.Comment: Accepted by Ap

Space charge behaviour in epoxy laminates under high constant electric field

The development of space charge in insulating materials is one of the main causes of their electrical ageing. The pulsed electro-acoustic method is often used to determine space charge distribution, but the signal analysis in the case of laminate structures is much more complex to analyse. In this paper the authors describe and use a simulated signal in order to study laminates made of epoxy resin and fibre mat. The relatively large conductivity of the fibres compared with that of the resin seems to produce a rapid charge dissociation and recombination in the fibres. Under voltage the presence of fibres close to an electrode seems to promote charge injection