Simulations of MHD Instabilities in Intracluster Medium Including Anisotropic Thermal Conduction

We perform a suite of simulations of cooling cores in clusters of galaxies in order to investigate the effect of the recently discovered heat flux buoyancy instability (HBI) on the evolution of cores. Our models follow the 3-dimensional magnetohydrodynamics (MHD) of cooling cluster cores and capture the effects of anisotropic heat conduction along the lines of magnetic field, but do not account for the cosmological setting of clusters or the presence of AGN. Our model clusters can be divided into three groups according to their final thermodynamical state: catastrophically collapsing cores, isothermal cores, and an intermediate group whose final state is determined by the initial configuration of magnetic field. Modeled cores that are reminiscent of real cluster cores show evolution towards thermal collapse on a time scale which is prolonged by a factor of ~2-10 compared with the zero-conduction cases. The principal effect of the HBI is to re-orient field lines to be perpendicular to the temperature gradient. Once the field has been wrapped up onto spherical surfaces surrounding the core, the core is insulated from further conductive heating (with the effective thermal conduction suppressed to less than 1/100th of the Spitzer value) and proceeds to collapse. We speculate that, in real clusters, the central AGN and possibly mergers play the role of "stirrers," periodically disrupting the azimuthal field structure and allowing thermal conduction to sporadically heat the core.Comment: 16 pages, 3 tables, 17 figures, accepted to ApJ with minor revisions, to appear in Volume 704, Oct 20, 2009 issu

The Nature of the UV/X-Ray Absorber in PG 2302+029

We present Chandra X-ray observations of the radio-quiet QSO PG 2302+029. This quasar has a rare system of ultra-high velocity (-56,000 km/s) UV absorption lines that form in an outflow from the active nucleus (Jannuzi et al. 2003). The Chandra data indicate that soft X-ray absorption is also present. We perform a joint UV and X-ray analysis, using photoionization calculations, to detemine the nature of the absorbing gas. The UV and X-ray datasets were not obtained simultaneously. Nonetheless, our analysis suggests that the X-ray absorption occurs at high velocities in the same general region as the UV absorber. There are not enough constraints to rule out multi-zone models. In fact, the distinct broad and narrow UV line profiles clearly indicate that multiple zones are present. Our preferred estimates of the ionization and total column density in the X-ray absorber (log U=1.6, N_H=10^22.4 cm^-2) over predict the O VI 1032, 1038 absorption unless the X-ray absorber is also outflowing at ~56,000 km/s, but they over predict the Ne VIII 770, 780 absorption at all velocities. If we assume that the X-ray absorbing gas is outflowing at the same velocity of the UV-absorbing wind and that the wind is radiatively accelerated, then the outflow must be launched at a radius of < 10^15 cm from the central continuum source. The smallness of this radius casts doubts on the assumption of radiative acceleration.Comment: Accepted for Publication in Ap

Safety and pharmacokinetics of MM-302, a HER2-targeted antibody–liposomal doxorubicin conjugate, in patients with advanced HER2-positive breast cancer: A phase 1 dose-escalation study

BackgroundThis phase 1 dose-escalation trial studied MM-302, a novel HER2-targeted PEGylated antibody-liposomal doxorubicin conjugate, in HER2-positive locally advanced/metastatic breast cancer.MethodsPatients were enrolled in four cohorts: MM-302 monotherapy (8, 16, 30, 40, and 50 mg/m2 every 4 weeks [q4w]); MM-302 (30 or 40 mg/m2 q4w) plus trastuzumab (4 mg/kg q2w); MM-302 (30 mg/m2) plus trastuzumab (6 mg/kg) q3w; MM-302 (30 mg/m2) plus trastuzumab (6 mg/kg) and cyclophosphamide (450 mg/m2) q3w.ResultsSixty-nine patients were treated. The most common adverse events (AEs) were fatigue and nausea. Grade 3/4 AEs of special interest included neutropenia, fatigue, mucosal inflammation, anemia, thrombocytopenia, febrile neutropenia, and palmar-plantar erythrodysesthesia. The MTD was not reached. With MM-302 ≥ 30 mg/m2, overall response rate (ORR) was 13% and median progression-free survival (mPFS) 7.4 months (95% CI: 3·5-10·9) in all arms. In 25 anthracycline-naïve patients, ORR was 28·0% and mPFS 10·9 months (95% CI: 1·8-15·3). Imaging with 64Cu-labeled MM-302 visualized tumor-drug penetrance in tumors throughout the body, including the brain.ConclusionMM-302 monotherapy, in combination with trastuzumab, or trastuzumab plus cyclophosphamide, was well tolerated and showed promising efficacy. The selected phase 2 MM-302 dose was 30 mg/m2 plus 6 mg/kg trastuzumab q3w

The Ionized Gas and Nuclear Environment in NGC 3783. I. Time-Averaged 900 ks Chandra Grating Spectroscopy

We present results from a 900 ks exposure of NGC 3783 with the High-Energy Transmission Grating Spectrometer on board the Chandra X-ray Observatory. The resulting X-ray spectrum has the best combination of signal-to-noise and resolution ever obtained for an AGN. This spectrum reveals absorption lines from H-like and He-like ions of N, O, Ne, Mg, Al, Si, and S. There are also possible absorption lines from H-like and He-like Ar and Ca. We also identify inner-shell absorption from lower-ionization ions such as Si_VII-Si_XII and S_XII-S_XIV. The iron absorption spectrum is very rich; L-shell lines of Fe_XVII-Fe_XXIV are detected, strong complex of M-shell lines, and probable resonance lines from Fe_XXV. The absorption lines are blueshifted relative to the systemic velocity by a mean velocity of -590+-150 km/s. We resolve many of the absorption lines, and their mean FWHM is 820+-280 km/s. We do not find correlations between the velocity shifts or the FWHMs with the ionization potentials of the ions. Most absorption lines show asymmetry, having more extended blue wings than red wings. In O_VII we have resolved this asymmetry to be from an additional absorption system at ~ -1300 km/s. The two X-ray absorption systems are consistent in velocity shift and FWHM with the ones identified in the UV lines of C IV, N V, and H I. Equivalent width measurements for all lines are given and column densities are calculated for several ions. We resolve the narrow Fe_K\alpha line at 6398.2+-3.3 eV to have a FWHM of 1720+-360 km/s, which suggests that this narrow line may be emitted from the outer part of the broad line region or the inner part of the torus. We also detect a `Compton shoulder' redward of the narrow Fe_K\alpha line which indicates that it arises in cold, Compton-thick gas.Comment: 19 pages, 12 figures (2 in color), emulateapj5, accepted for publication in The Astrophysical Journal Supplement

The Ionized Gas and Nuclear Environment in NGC 3783 V. Variability and Modeling of the Intrinsic Ultraviolet Absorption

We present results on the location, physical conditions, and geometry of the outflow in the Seyfert 1 galaxy NGC 3783 from a study of the variable intrinsic UV absorption. Based on 18 observations with HST/STIS and 6 observations with FUSE, we find: 1) The absorption from the lowest-ionization species in each of the three strong kinematic components varied inversely with the continuum flux, indicating the ionization structure responded to changes in the photoionizing flux over the weekly timescales sampled by our observations. 2) A multi- component model with an unocculted NLR and separate BLR and continuum line-of-sight covering factors predicts saturation in several lines, consistent with the lack of observed variability. 3) Column densities for the individual metastable levels are measured from the resolved C III *1175 absorption complex observed in one component. Based on our computed metastable level populations, the electron density of this absorber is ~3x10^4 cm^-3. Photoionization modeling results place it at ~25 pc from the central source. 4) Using time-dependent calculations, we are able to reproduce the detailed variability observed in this absorber, and derive upper limits on the distances for the other components of 25-50 pc. 5) The ionization parameters derived for the higher ionization UV absorbers are consistent with the modeling results for the lowest-ionization X-ray component, but with smaller total column density. They have similar pressures as the three X-ray ionization components. These results are consistent with an inhomogeneous wind model for the outflow in NGC 3783. 6) Based on the predicted emission-line luminosities, global covering factor constraints, and distances derived for the UV absorbers, they may be identified with emission- line gas observed in the inner NLR of AGNs. (abridged)Comment: 30 pages, 18 figures (7 color), emulateapj, accepted for publication in The Astrophysical Journa

Flaring Behavior of the Quasar 3C~454.3 across the Electromagnetic Spectrum

We analyze the behavior of the parsec-scale jet of the quasar 3C~454.3 during pronounced flaring activity in 2005-2008. Three major disturbances propagated down the jet along different trajectories with Lorentz factors $\Gamma>$10. The disturbances show a clear connection with millimeter-wave outbursts, in 2005 May/June, 2007 July, and 2007 December. High-amplitude optical events in the $R$-band light curve precede peaks of the millimeter-wave outbursts by 15-50 days. Each optical outburst is accompanied by an increase in X-ray activity. We associate the optical outbursts with propagation of the superluminal knots and derive the location of sites of energy dissipation in the form of radiation. The most prominent and long-lasting of these, in 2005 May, occurred closer to the black hole, while the outbursts with a shorter duration in 2005 Autumn and in 2007 might be connected with the passage of a disturbance through the millimeter-wave core of the jet. The optical outbursts, which coincide with the passage of superluminal radio knots through the core, are accompanied by systematic rotation of the position angle of optical linear polarization. Such rotation appears to be a common feature during the early stages of flares in blazars. We find correlations between optical variations and those at X-ray and $\gamma$-ray energies. We conclude that the emergence of a superluminal knot from the core yields a series of optical and high-energy outbursts, and that the mm-wave core lies at the end of the jet's acceleration and collimation zone.Comment: 57 pages, 23 figures, 8 tables (submitted to ApJ

Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline

The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline

A direct physical interaction between Nanog and Sox2 regulates embryonic stem cell self-renewal

Embryonic stem (ES) cell self-renewal efficiency is determined by the Nanog protein level. However, the protein partners of Nanog that function to direct self-renewal are unclear. Here, we identify a Nanog interactome of over 130 proteins including transcription factors, chromatin modifying complexes, phosphorylation and ubiquitination enzymes, basal transcriptional machinery members, and RNA processing factors. Sox2 was identified as a robust interacting partner of Nanog. The purified Nanog–Sox2 complex identified a DNA recognition sequence present in multiple overlapping Nanog/Sox2 ChIP-Seq data sets. The Nanog tryptophan repeat region is necessary and sufficient for interaction with Sox2, with tryptophan residues required. In Sox2, tyrosine to alanine mutations within a triple-repeat motif (S X T/S Y) abrogates the Nanog–Sox2 interaction, alters expression of genes associated with the Nanog-Sox2 cognate sequence, and reduces the ability of Sox2 to rescue ES cell differentiation induced by endogenous Sox2 deletion. Substitution of the tyrosines with phenylalanine rescues both the Sox2–Nanog interaction and efficient self-renewal. These results suggest that aromatic stacking of Nanog tryptophans and Sox2 tyrosines mediates an interaction central to ES cell self-renewal