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

OMCat: Catalogue of Serendipitous Sources Detected with the XMM-Newton Optical Monitor

The Optical Monitor Catalogue of serendipitous sources (OMCat) contains entries for every source detected in the publicly available XMM-Newton Optical Monitor (OM) images taken in either the imaging or ``fast'' modes. Since the OM is coaligned and records data simultaneously with the X-ray telescopes on XMM-Newton, it typically produces images in one or more near-UV/optical bands for every pointing of the observatory. As of the beginning of 2006, the public archive had covered roughly 0.5% of the sky in 2950 fields. The OMCat is not dominated by sources previously undetected at other wavelengths; the bulk of objects have optical counterparts. However, the OMCat can be used to extend optical or X-ray spectral energy distributions for known objects into the ultraviolet, to study at higher angular resolution objects detected with GALEX, or to find high-Galactic-latitude objects of interest for UV spectroscopy.Comment: 25 pages, 22 figures, submitted to PAS

Inverse Magnetoresistance of Molecular Junctions

We present calculations of spin-dependent electron transport through single organic molecules bridging pairs of iron nanocontacts. We predict the magnetoresistance of these systems to switch from positive to negative with increasing applied bias for both conducting and insulating molecules. This novel inverse magnetoresistance phenomenon is robust, does not depend on the presence of impurities, and is unique to molecular and atomic nanoscale magnetic junctions. Its physical origin is identified and its relevance to experiment and to potential technological applications is discussed.Comment: 5 pages, 3 figures; published version Phys. Rev.

A Prediction of Observable Rotation in the ICM of Abell 3266

We present a numerical Hydro+N-body model of A3266 whose X-ray surface brightness, temperature distribution, and galaxy spatial and velocity distribution data are consistent with the A3266 data. The model is an old (~3 Gyr), off-axis merger having a mass ratio of ~2.5:1. The less massive subcluster in the model is moving on a trajectory from southwest to northeast passing on the western side of the dominant cluster while moving into the plane of the sky at ~45 degrees. Off-axis mergers such as this one are an effective mechanism for transferring angular momentum to the intracluster medium (ICM), making possible a large scale rotation of the ICM. We demonstrate here that the ICM rotation predicted by our fully 3-dimensional model of A3266 is observable with current technology. As an example, we present simulated observations assuming the capabilities of the high resolution X-ray spectrometer (XRS) which was to have flown on Astro-E.Comment: 9 pages, 7 postscript figures, Fig. 3 and 6 are color postscript, Accepted for publication in the Astrophysical Journa

Physics of the Merging Clusters Cygnus A, A3667, and A2065

We present ASCA gas temperature maps of the nearby merging galaxy clusters Cygnus A, A3667, and A2065. Cygnus A appears to have a particularly simple merger geometry that allows an estimate of the subcluster collision velocity from the observed temperature variations. We estimate it to be ~2000 km/s. Interestingly, this is similar to the free-fall velocity that the two Cygnus A subclusters should have achieved at the observed separation, suggesting that merger has been effective in dissipating the kinetic energy of gas halos into thermal energy, without channeling its major fraction elsewhere (e.g., into turbulence). In A3667, we may be observing a spatial lag between the shock front seen in the X-ray image and the corresponding rise of the electron temperature. A lag of the order of hundreds of kiloparsecs is possible due to the combination of thermal conduction and a finite electron-ion equilibration time. Forthcoming better spatial resolution data will allow a direct measurement of these phenomena using such lags. A2065 has gas density peaks coincident with two central galaxies. A merger with the collision velocity estimated from the temperature map should have swept away such peaks if the subcluster total mass distributions had flat cores in the centers. The fact that the peaks have survived (or quickly reemerged) suggests that the gravitational potential also is strongly peaked. Finally, the observed specific entropy variations in A3667 and Cygnus A indicate that energy injection from a single major merger may be of the order of the full thermal energy of the gas. We hope that these order of magnitude estimates will encourage further work on hydrodynamic simulations, as well as more quantitative representation of the simulation results.Comment: Corrected the Cyg-A figure (errors shown were 1-sigma not 90%); text unchanged. ApJ in press. Latex, 5 pages, 3 figures (2 color), uses emulateapj.st

Theoretical Study of Spin-dependent Electron Transport in Atomic Fe Nanocontacts

We present theoretical predictions of spintronic transport phenomena that should be observable in ferromagnetic Fe nanocontacts bridged by chains of Fe atoms. We develop appropriate model Hamiltonians based on semi-empirical considerations and the known electronic structure of bulk Fe derived from ab initio density functional calculations. Our model is shown to provide a satisfactory description of the surface properties of Fe nano-clusters as well as bulk properties. Lippmann-Schwinger and Green's function techniques are used together with Landauer theory to predict the current, magneto-resistance, and spin polarization of the current in Fe nanocontacts bridged by atomic chains under applied bias. Unusual device characteristics are predicted including negative magneto-resistance and spin polarization of the current, as well as spin polarization of the current for anti-parallel magnetization of the Fe nanocontacts under moderate applied bias. We explore the effects that stretching the atomic chain has on the magneto-resistance and spin polarization and predict a cross-over regime in which the spin polarization of the current for parallel magnetization of the contacts switches from negative to positive. We find resonant transmission due to dangling bond formation on tip atoms as the chain is stretched through its breaking point to play an important role in spin-dependent transport in this regime. The physical mechanisms underlying the predicted phenomena are discussed.Comment: 13 pages, 6 figures, Accepted for publication in Physical Review

Merger Dynamics of the Pair of Galaxy Clusters -- A399 and A401

Convincing evidence of a past interaction between two rich clusters A399 and A401 was recently found by the X-ray imaging observations. In this paper we examine the structure and dynamics of this pair of galaxy clusters. A mixture-modeling algorithm has been applied to obtain a robust partition into two clusters, which allows us to discuss the virial mass and velocity distribution for each cluster. Assuming that these two clusters follow a linear orbit and they have once experienced a close encounter, we model the binary cluster as a two-body system. As a result, four gravitationally bound solutions are obtained. The recent X-ray observations seem to favor a scenario in which the two clusters with a true separation of $5.4h^{-1}$ Mpc are currently expanding at 583 km/s along the direction with a projection angle of 67.5 degree, and they will reach a maximum extent of $5.65h^{-1}$ Mpc in about $1.0h^{-1}$ Gyr.Comment: 11 pages, including 6 EPS figures and 4 tables, uses chjaa.cls, Accepted by the ChJA