Determination of the Her-2/neu gene amplification status in cytologic breast cancer specimens using automated silver-enhanced in-situ hybridization (SISH)

Silver-enhanced in-situ hybridization (SISH) is an emerging tool for the determination of the Her-2/neu amplification status in breast cancer. SISH is technically comparable to fluorescence in-situ hybridization (FISH) but does not require a fluorescence microscope for its interpretation. Although recent studies on histologic evaluations of SISH are promising, we aimed to evaluate its performance on 71 cytologic breast cancer specimens with the new combined Her-2/Chr17 probe. Her-2/neu status as routinely determined by FISH was available for all patients. We found SISH signals in cytologic cell blocks and smear specimens easy to evaluate in most cases. Small numbers of tumor cells and difficulties in identifying tumor cells in lymphocyte-rich backgrounds were limiting factors. Her-2/neu status, as determined by Her-2/Chr17 SISH, was basically identical to the results of the corresponding FISH. The discrepancies were mainly owing to the heterogeneity of Her-2/neu amplification in the tumor tissue. Interobserver agreement for the SISH evaluation was high (kappa value: 0.972). We conclude that Her-2/Chr17 SISH is a useful and accurate method for the evaluation of the Her-2/neu gene amplification status in cytologic breast cancer specimens, particularly in metastatic breast cancer lesions. The advantages of signal permanency and bright-field microscopic result interpretation make this technique an attractive alternative to the current FISH-based gold standard

Evolution of the Cluster Correlation Function

We study the evolution of the cluster correlation function and its richness-dependence from z = 0 to z = 3 using large-scale cosmological simulations. A standard flat LCDM model with \Omega_m = 0.3 and, for comparison, a tilted \Omega_m = 1 model, TSCDM, are used. The evolutionary predictions are presented in a format suitable for direct comparisons with observations. We find that the cluster correlation strength increases with redshift: high redshift clusters are clustered more strongly (in comoving scale) than low redshift clusters of the same mass. The increased correlations with redshift, in spite of the decreasing mass correlation strength, is caused by the strong increase in cluster bias with redshift: clusters represent higher density peaks of the mass distribution as the redshift increases. The richness-dependent cluster correlation function, presented as the correlation-scale versus cluster mean separation relation, R_0 - d, is found to be, remarkably, independent of redshift to z <~ 2 for LCDM and z <~ 1 for TCDM (for a fixed correlation function slope and cluster mass within a fixed comoving radius). The non-evolving R_0 - d relation implies that both the comoving clustering scale and the cluster mean separation increase with redshift for the same mass clusters so that the R_0 - d relation remains essentially unchanged. The evolution of the R_0 - d relation from z ~ 0 to z ~ 3 provides an important new tool in cosmology; it can be used to break degeneracies that exist at z ~ 0 and provide precise determination of cosmological parameters.Comment: AASTeX, 15 pages, including 5 figures, accepted version for publication in ApJ, vol.603, March 200

Chandra detection of extended X-ray emission from the recurrent nova RS Ophiuchi

Radio, infrared, and optical observations of the 2006 eruption of the symbiotic recurrent nova RS Ophiuchi (RS Oph) showed that the explosion produced non-spherical ejecta. Some of this ejected material was in the form of bipolar jets to the east and west of the central source. Here we describe Xray observations taken with the Chandra X-ray Observatory one and a half years after the beginning of the outburst that reveal narrow, extended structure with a position angle of approximately 300 degrees (east of north). Although the orientation of the extended feature in the X-ray image is consistent with the readout direction of the CCD detector, extensive testing suggests that the feature is not an artifact. Assuming it is not an instrumental effect, the extended X-ray structure shows hot plasma stretching more than 1,900 AU from the central binary (taking a distance of 1.6 kpc). The X-ray emission is elongated in the northwest direction - in line with the extended infrared emission and some minor features in the published radio image. It is less consistent with the orientation of the radio jets and the main bipolar optical structure. Most of the photons in the extended X-ray structure have energies of less than 0.8 keV. If the extended X-ray feature was produced when the nova explosion occurred, then its 1".2 length as of 2007 August implies that it expanded at an average rate of more than 2 mas/d, which corresponds to a flow speed of greater than 6,000 km/s (d/1.6 kpc) in the plane of the sky. This expansion rate is similar to the earliest measured expansion rates for the radio jets.Comment: accepted in Ap

The Critical Hopping Parameter in O(a) improved Lattice QCD

We calculate the critical value of the hopping parameter, $\kappa_c$, in O(a) improved Lattice QCD, to two loops in perturbation theory. We employ the Sheikholeslami-Wohlert (clover) improved action for Wilson fermions. The quantity which we study is a typical case of a vacuum expectation value resulting in an additive renormalization; as such, it is characterized by a power (linear) divergence in the lattice spacing, and its calculation lies at the limits of applicability of perturbation theory. The dependence of our results on the number of colors $N$, the number of fermionic flavors $N_f$, and the clover parameter $c_{SW}$, is shown explicitly. We compare our results to non perturbative evaluations of $\kappa_c$ coming from Monte Carlo simulations.Comment: 11 pages, 2 EPS figures. The only change with respect to the original version is inclusion of the standard formulae for the gauge fixing and ghost parts of the action. Accepted for publication in Physical Review

Dynamical overlap fermions, results with hybrid Monte-Carlo algorithm

We present first, exploratory results of a hybrid Monte-Carlo algorithm for dynamical, n_f=2, four-dimensional QCD with overlap fermions. As expected, the computational requirements are typically two orders of magnitude larger for the dynamical overlap formalism than for the more conventional (Wilson or staggered) formulations.Comment: 13 pages, 2 figure

Cystatins as calpain inhibitors: Engineered chicken cystatin- and stefin B-kininogen domain 2 hybrids support a cystatin-like mode of interaction with the catalytic subunit of μ-calpain

Within the cystatin superfamily, only kininogen domain 2 (KD2) is able to inhibit μ- and m-calpain. In an attempt to elucidate the structural requirements of cystatins for calpain inhibition, we constructed recombinant hybrids of human stefin B (an intracellular family 1 cystatin) with KD2 and Delta L110 deletion mutants of chicken cystatin-KD2 hybrids. Substitution of the N-terminal contact region of stefin B by the corresponding KD2 sequence resulted in a calpain inhibitor of K-i = 188 nM. Deletion of L110, which forms a beta -bulge in family 1 and 2 cystatins but is lacking in KD2, improved inhibition of mu -calpain 4- to 8-fold. All engineered cystatins were temporary inhibitors of calpain due to slow substrate-like cleavage of a single peptide bond corresponding to Gly9-Ala10 in chicken cystatin. Biomolecular interaction analysis revealed that, unlike calpastatin, the cystatin-type inhibitors do not bind to the calmodulin-like domain of the small subunit of calpain, and their interaction with the mu -calpain heterodimer is completely prevented by a synthetic peptide comprising subdomain B of calpastatin domain 1. Based on these results we propose that (i) cystatin-type calpain inhibitors interact with the active site of the catalytic domain of calpain in a similar cystatin-like mode as with papain and (ii) the potential for calpain inhibition is due to specific subsites within the papain-binding regions of the general cystatin fold

Swift observations of the 2006 outburst of the recurrent nova RS Ophiuchi: II. 1D hydrodynamical models of wind driven shocks

Following the early Swift X-ray observations of the latest outburst of the recurrent nova RS Ophiuchi in February 2006 (Paper I), we present new 1D hydrodynamical models of the system which take into account all three phases of the remnant evolution. The models suggest a novel way of modelling the system by treating the outburst as a sudden increase then decrease in wind mass-loss rate and velocity. The differences between this wind model and previous Primakoff-type simulations are described. A more complex structure, even in 1D, is revealed through the presence of both forward and reverse shocks, with a separating contact discontinuity. The effects of radiative cooling are investigated and key outburst parameters such as mass-loss rate, ejecta velocity and mass are varied. The shock velocities as a function of time are compared to the ones derived in Paper I. We show how the manner in which the matter is ejected controls the evolution of the shock and that for a well-cooled remnant, the shock deceleration rate depends on the amount of energy that is radiated away.Comment: 9 pages, 5 figure

Supermassive Black Holes and Galaxy Formation

The formation of supermassive black holes (SMBH) is intimately related to galaxy formation, although precisely how remains a mystery. I speculate that formation of, and feedback from, SMBH may alleviate problems that have arisen in our understanding of the cores of dark halos of galaxies.Comment: Talk at conference on Matter in the Universe, March 2001, ISSI Ber

String amplitudes in arbitrary dimensions

We calculate gravitational dressed tachyon correlators in non critcal dimensions. The 2D gravity part of our theory is constrained to constant curvature. Then scaling dimensions of gravitational dressed vertex operators are equal to their bare conformal dimensions. Considering the model as d+2 dimensional critical string we calculate poles of generalized Shapiro-Virasoro amplitudes.Comment: 14 page

Quantitative analysis of cell types during growth and morphogenesis in Hydra

Tissue maceration was used to determine the absolute number and the distribution of cell types in Hydra. It was shown that the total number of cells per animal as well as the distribution of cells vary depending on temperature, feeding conditions, and state of growth. During head and foot regeneration and during budding the first detectable change in the cell distribution is an increase in the number of nerve cells at the site of morphogenesis. These results and the finding that nerve cells are most concentrated in the head region, diminishing in density down the body column, are discussed in relation to tissue polarity