4,909 research outputs found
Dissipative and nonaxisymmetric standard-MRI in Kepler disks
Deviations from axial symmetry are necessary to maintain self-sustained
MRI-turbulence. We define the parameters region where nonaxisymmetric MRI is
excited and study dependence of the unstable modes structure and growth rates
on the relevant parameters. We solve numerically the linear eigenvalue problem
for global axisymmetric and nonaxisymmetric modes of standard-MRI in Keplerian
disks with finite diffusion. For small magnetic Prandtl number the microscopic
viscosity completely drops out from the analysis so that the stability maps and
the growth rates expressed in terms of the magnetic Reynolds number Rm and the
Lundquist number S do not depend on the magnetic Prandtl number Pm. The minimum
magnetic field for onset of nonaxisymmetric MRI grows with Rm. For given S all
nonaxisymmetric modes disappear for sufficiently high Rm. This behavior is a
consequence of the radial fine-structure of the nonaxisymmetric modes resulting
from the winding effect of differential rotation. It is this fine-structure
which presents severe resolution problems for the numerical simulation of MRI
at large Rm. For weak supercritical magnetic fields only axisymmetric modes are
unstable. Nonaxisymmetric modes need stronger fields and not too fast rotation.
If Pm is small its real value does not play any role in MRI.Comment: 4 pages, 6 figures, A&A Lette
MHD simulations of the magnetorotational instability in a shearing box with zero net flux. II. The effect of transport coefficients
We study the influence of the choice of transport coefficients (viscosity and
resistivity) on MHD turbulence driven by the magnetorotational instability
(MRI) in accretion disks. We follow the methodology described in paper I: we
adopt an unstratified shearing box model and focus on the case where the net
vertical magnetic flux threading the box vanishes. For the most part we use the
finite difference code ZEUS, including explicit transport coefficients in the
calculations. However, we also compare our results with those obtained using
other algorithms (NIRVANA, the PENCIL code and a spectral code) to demonstrate
both the convergence of our results and their independence of the numerical
scheme. We find that small scale dissipation affects the saturated state of MHD
turbulence. In agreement with recent similar numerical simulations done in the
presence of a net vertical magnetic flux, we find that turbulent activity
(measured by the rate of angular momentum transport) is an increasing function
of the magnetic Prandtl number Pm for all values of the Reynolds number Re that
we investigated. We also found that turbulence disappears when the Prandtl
number falls below a critical value Pm_c that is apparently a decreasing
function of Re. For the limited region of parameter space that can be probed
with current computational resources, we always obtained Pm_c>1. We conclude
that the magnitudes of the transport coefficients are important in determining
the properties of MHD turbulence in numerical simulations in the shearing box
with zero net flux, at least for Reynolds numbers and magnetic Prandtl numbers
that are such that transport is not dominated by numerical effects and thus can
be probed using current computational resources.Comment: 10 pages, 13 figures, accepted in A&A. Numerical results improved,
minor changes in the tex
KLF4-SQSTM1/p62-associated prosurvival autophagy contributes to carfilzomib resistance in multiple myeloma models.
Multiple myeloma (MM) is an incurable clonal plasma cell malignancy. Because of a high rate of immunoglobulin synthesis, the endoplasmic reticulum of MM cells is subjected to elevated basal levels of stress. Consequently, proteasome inhibitors, which exacerbate this stress by inhibiting ubiquitin-proteasome-mediated protein degradation, are an important new class of chemotherapeutic agents being used to combat this disease. However, MM cells still develop resistance to proteasome inhibitors such as carfilzomib. Toward this end, we have established carfilzomib-resistant derivatives of MM cell lines. We found that resistance to carfilzomib was associated with elevated levels of prosurvival autophagy, and Kruppel-like factor 4 (KLF4) was identified as a contributing factor. Expression levels as well as nuclear localization of KLF4 protein were elevated in MM cells with acquired carfilzomib resistance. Chromatin immunoprecipitations indicated that endogenous KLF4 bound to the promoter regions of the SQSTM1 gene encoding the ubiquitin-binding adaptor protein sequestosome/p62 that links the proteasomal and autophagic protein degradation pathways. Ectopic expression of KLF4 induced upregulation of SQSTM1. On the other hand, inhibitors of autophagy sensitized MM cells to carfilzomib, even in carfilzomib-resistant derivatives having increased expression of the multidrug resistance protein P-glycoprotein. Thus, we report here a novel function for KLF4, one of the Yamanaka reprogramming factors, as being a contributor to autophagy gene expression which moderates preclinical proteasome inhibitor efficacy in MM
Impact of dimensionless numbers on the efficiency of MRI-induced turbulent transport
The magneto-rotational instability is presently the most promising source of
turbulent transport in accretion disks. However, some important issues still
need to be addressed to quantify the role of MRI in disks; in particular no
systematic investigation of the role of the physical dimensionless parameters
of the problem on the dimensionless transport has been undertaken yet. First,
we complete existing investigations on the field strength dependence by showing
that the transport in high magnetic pressure disks close to marginal stability
is highly time-dependent and surprisingly efficient. Second, we bring to light
a significant dependence of the global transport on the magnetic Prandtl
number, with for the explored range: and
( being in the range 0.25 to 0.5). We show that the
dimensionless transport is not correlated to the dimensionless linear growth
rate, contrarily to a largely held expectation. More generally, these results
stress the need to control dissipation processes in astrophysical simulations.Comment: 11 pages, 11 figures, accepted to MNRA
Transition from collisionless to collisional MRI
Recent calculations by Quataert et al. (2002) found that the growth rates of
the magnetorotational instability (MRI) in a collisionless plasma can differ
significantly from those calculated using MHD. This can be important in hot
accretion flows around compact objects. In this paper we study the transition
from the collisionless kinetic regime to the collisional MHD regime, mapping
out the dependence of the MRI growth rate on collisionality. A kinetic closure
scheme for a magnetized plasma is used that includes the effect of collisions
via a BGK operator. The transition to MHD occurs as the mean free path becomes
short compared to the parallel wavelength 2\pi/k_{\Par}. In the weak magnetic
field regime where the Alfv\'en and MRI frequencies are small compared
to the sound wave frequency k_{\Par} c_0, the dynamics are still effectively
collisionless even if , so long as the collision frequency \nu
\ll k_{\Par} c_{0}; for an accretion flow this requires \nu \lsim \Omega
\sqrt{\beta}. The low collisionality regime not only modifies the MRI growth
rate, but also introduces collisionless Landau or Barnes damping of long
wavelength modes, which may be important for the nonlinear saturation of the
MRI.Comment: 20 pages, 4 figures, submitted to ApJ with a clearer derivation of
anisotropic pressure closure from drift kinetic equatio
On the Polish doughnut accretion disk via the effective potential approach
We revisit the Polish doughnut model of accretion disks providing a
comprehensive analytical description of the Polish doughnut structure. We
describe a perfect fluid circularly orbiting around a Schwarzschild black hole,
source of the gravitational field, by the effective potential approach for the
exact gravitational and centrifugal effects. This analysis leads to a detailed,
analytical description of the accretion disk, its toroidal surface, the
thickness, the distance from the source. We determine the variation of these
features with the effective potential and the fluid angular momentum. Many
analytical formulas are given. In particular it turns out that the distance
from the source of the inner surface of the torus increases with increasing
fluid angular momentum but decreases with increasing energy function defined as
the value of the effective potential for that momentum. The location of torus
maximum thickness moves towards the external regions of the surface with
increasing angular momentum, until it reaches a maximum an then decreases.
Assuming a polytropic equation of state we investigate some specific cases.Comment: 33 pages, 28 figures, 1 table. This is a revised version to meet the
published articl
Increased expression of the tight junction protein TJP1/ZO-1 is associated with upregulation of TAZ-TEAD activity and an adult tissue stem cell signature in carfilzomib-resistant multiple myeloma cells and high-risk multiple myeloma patients
Tight junction protein 1 (TJP1) has recently been proposed as a biomarker to identify multiple myeloma (MM) patients most likely to respond to bortezomiband carfilzomib-based proteasome inhibitor regimens. Herein we report increased expression of TJP1 during the adaptive response mediating carfilzomib resistance in the LP-1/Cfz MM cell line. Moreover, increased TJP1 expression delineated a subset of relapsed/refractory MM patients on bortezomib-based therapy sharing an LP-1/Cfzlike phenotype characterized by activation of interacting transcriptional effectors of the Hippo signaling cascade (TAZ and TEAD1) and an adult tissue stem cell signature. siRNA-mediated knockdown of TJP1 or TAZ/TEAD1 partially sensitized LP-1/Cfz cells to carfilzomib. Connectivity Map analysis identified translation inhibitors as candidate therapeutic agents targeting this molecular phenotype. We confirmed this prediction by showing that homoharringtonine (omacetaxine mepesuccinate) — the first translation inhibitor to be approved by the U.S. Food and Drug Administration — displayed potent cytotoxic activity on LP-1/Cfz cells. Homoharringtonine treatment reduced the levels of TAZ and TEAD1 as well as the MM-protective proteins Nrf2 and MCL1. Thus, our data suggest the importance of further studies evaluating translation inhibitors in relapsed/refractory MM. On the other hand, use of TJP1 as a MM biomarker for proteasome inhibitor sensitivity requires careful consideration
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