487 research outputs found
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
Response of Natural and Cultivated Hay Meadows to Fertilizer Applied by Small Scale Livestock Farmers in the Mountainous Sandzak Region of Serbia
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
Inhibition of the mitochondrial pyruvate carrier protects from excitotoxic neuronal death.
Glutamate is the dominant excitatory neurotransmitter in the brain, but under conditions of metabolic stress it can accumulate to excitotoxic levels. Although pharmacologic modulation of excitatory amino acid receptors is well studied, minimal consideration has been given to targeting mitochondrial glutamate metabolism to control neurotransmitter levels. Here we demonstrate that chemical inhibition of the mitochondrial pyruvate carrier (MPC) protects primary cortical neurons from excitotoxic death. Reductions in mitochondrial pyruvate uptake do not compromise cellular energy metabolism, suggesting neuronal metabolic flexibility. Rather, MPC inhibition rewires mitochondrial substrate metabolism to preferentially increase reliance on glutamate to fuel energetics and anaplerosis. Mobilizing the neuronal glutamate pool for oxidation decreases the quantity of glutamate released upon depolarization and, in turn, limits the positive-feedback cascade of excitotoxic neuronal injury. The finding links mitochondrial pyruvate metabolism to glutamatergic neurotransmission and establishes the MPC as a therapeutic target to treat neurodegenerative diseases characterized by excitotoxicity
β3-integrin is required for differentiation in OC-2 cells derived from mammalian embryonic inner ear
Background
The mammalian inner ear contains the organ of Corti which is responsible for the conversion of sound into neuronal signals. This specialised epithelial tissue is the product of a complex developmental process where a common precursor cell type differentiates into the sound transducing hair cells and the non-innervated supporting cells. We hypothesised that integrin proteins, which are involved in cell attachment to extracellular matrix proteins and cellular signalling, play a role in the differentiation process of the precursor inner ear epithelial cells. To test our hypothesis we have utilised a cell line (OC-2) derived from E13 embryonic immortomouse inner ears. In vitro, by switching the incubation temperature from 33°C to 39°C, the OC-2 cells can be induced to differentiate and express hair cells markers, such as Myosin VIIa. The OC-2 cells are thus a useful model system for testing mechanism of hair cells differentiation.
Results
We have identified 4 integrin subunits which are expressed in OC-2 cells: α6, αv, β1 and β3. Among these, the relative level of expression of the αv, β1 and β3 subunits increased in a time dependent manner when the cells were exposed to the differentiating temperature of 39°C, most notably so for β3 which was not detectable at 33°C. Treatment of fully differentiated OC-2 cells with siRNA against the four integrin subunits reduced the expression of not only the respective integrin proteins but also of the hair cell marker Myosin VIIa. Conversely over-expression of β3 was sufficient to induce the expression of Myosin VIIa at 33°C.
Conclusions
Our data demonstrate that modulation of integrin expression is associated with the differentiation process of the OC-2 cells. This suggests that the maturation of the organ of Corti, from where OC-2 cells are derived, may also depend on changes of gene expression associated with integrin expression
Analysis of ontogenetic growth trends in two marine Antarctic bivalves Yoldia eightsi and Laternula elliptica: Implications for sclerochronology
There is an increasing use of marine species as paleoclimate recorders for the marine realm. These archives provide novel baseline records of past oceanographic variability in regions devoid of instrumental observations. Here we report results of a study of the ontogenetic growth pattern of two Antarctic marine bivalve molluscs: Yoldia eightsi and Laternula elliptica from West Antarctic Peninsula populations using negative exponential detrending technique and multi-taper method spectral analysis. Our data show the growth of both Y. eightsi and L. elliptica follow a general negative exponential trend over their longevity. However, our analyses also identified an innate 9.06 year periodic endogenous growth rhythm in the growth increment pattern of Y. eightsi and two innate periodic growth rhythms, 5 and 6.6 year period, were found in L. elliptica. We hypothesize that the Y. eightsi endogenous growth rhythm may be related to the reallocation of energetic resources between somatic growth and gametogenesis although more biological data are required to test this hypothesis. Further work into L. elliptica biology is required to understand the possible meaning of the innate growth rhythms found for this species. The identification growth rhythms is important not only for their biological significance but also in sclerochronological analysis because of their importance in developing paleoenvironmental reconstructions
Co-dependent and Interdigitated: Dual Quorum Sensing Systems Regulate Conjugative Transfer of the Ti Plasmid and the At Megaplasmid in Agrobacterium tumefaciens 15955
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
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