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

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

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

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 $\omega$ are small compared to the sound wave frequency k_{\Par} c_0, the dynamics are still effectively collisionless even if $\omega \ll \nu$, 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

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

Mycorrhizal status of indigenous tree species in a forest biome of the Eastern Cape, South Africa

Mycorrhizal fungi are intimately associated with plant roots, affecting plant growth, health and increasing the plants' tolerance to environmental stress. Several mycorrhizal types are recognized based primarily on morphological characteristics within plant roots. When considering propagation and management of an indigenous plant species, it is essential to know its mycorrhizal status. Root samples from 17 tree species common to the pockets of forest in the Eastern Cape province, and representing the families Rubiaceae, Scrophulariaceae, Oleaceae, Podocarpaceae, Myrsinaceae, Anacardiaceae, Caesalpinoideae, Papilionoideae, Rutaceae, Meliaceae, Celastraceae, Flacouticeae and Ebenaceae, were sampled and examined for mycorrhizal colonization. Microscopic examination of all the species produced evidence of morphological structures indicative of endomycorrhizal associations as indicated by the presence of intercellular hyphae combined with vesicles, arbuscules or hyphal coils. Hyphal coils (also known as Paris-type associations) appeared to be abundant, especially within the Cassine genus. Arbuscules (also known as Arum-type associations) were scarce but sometimes present, and vesicles were prolific in Olea capensis. Most of the tree species examined have been assigned arbuscular mycorrhizal status. No ectomycorrhizal associations were recorde

Studies of Connecticut Hardwoods: The Form of Hardwoods and Volume Tables on a Form Quotient Basis

SATISFACTORY volume tables for Connecticut Hardwoods have been . lacking. Considering the fact that the forestry movement within the state started a quarter of a century ago, this condition may seem strange. The scarcity of large bodies of timber, the diverse mixture of species in the average stand requiring several volume tables, and the fact that timber estimating as a business is of relatively lower importance here than in the more heavily timbered regions, account for the failure to develop volume tables. Foresters working within the region have been content to estimate timber by log unit methods or to adapt volume tables made for other localities to fit Connecticut conditions