Magnetohydrodynamic Oscillations in the Solar Corona and Earth's Magnetosphere: Towards Consolidated Understanding

Magnetohydrodynamic (MHD) oscillatory processes in di�erent plasma systems, such as the corona of the Sun and the Earth's magnetosphere show interesting similarities and di�erences, which so far received little attention and remain underexploited. The successful commissioning within the past ten years of SDO, Hinode, STEREO and THEMIS spacecraft, in combination with matured analysis of data from earlier spacecraft (Wind, SOHO, ACE, Cluster, TRACE and RHESSI) makes it very timely to survey the breadth of observations giving evidence for MHD oscillatory processes in solar and space plasmas, and state-of-the-art theoretical modelling. The paper reviews several important topics, such as Alfv�enic resonances and mode conversion; MHD waveguides, such as the magnetotail, coronal loops, coronal streamers; mechanisms for periodicities produced in energy releases during substorms and solar flares, possibility of Alfv�enic resonators along open �eld lines; possible drivers of MHD waves; diagnostics of plasmas with MHD waves; interaction of MHD waves with partly-ionised boundaries (ionosphere and chromosphere). The review is mainly oriented to specialists in magnetospheric physics and solar physics, but not familiar with speci�cs of the adjacent research �elds

Human GBP1 binds LPS to initiate assembly of a caspase-4 activating platform on cytosolic bacteria

The human non-canonical inflammasome controls caspase-4 activation and gasdermin-D-dependent pyroptosis in response to cytosolic bacterial lipopolysaccharide (LPS). Since LPS binds and oligomerizes caspase-4, the pathway is thought to proceed without dedicated LPS sensors or an activation platform. Here we report that interferon-induced guanylate-binding proteins (GBPs) are required for non-canonical inflammasome activation by cytosolic Salmonella or upon cytosolic delivery of LPS. GBP1 associates with the surface of cytosolic Salmonella seconds after bacterial escape from their vacuole, initiating the recruitment of GBP2-4 to assemble a GBP coat. The GBP coat then promotes the recruitment of caspase-4 to the bacterial surface and caspase activation, in absence of bacteriolysis. Mechanistically, GBP1 binds LPS with high affinity through electrostatic interactions. Our findings indicate that in human epithelial cells GBP1 acts as a cytosolic LPS sensor and assembles a platform for caspase-4 recruitment and activation at LPS-containing membranes as the first step of non-canonical inflammasome signaling

Magnetohydrodynamic oscillations in the solar corona and Earth's magnetosphere : towards consolidated understanding

Magnetohydrodynamic (MHD) oscillatory processes in different plasma systems, such as the corona of the Sun and the Earth’s magnetosphere, show interesting similarities and differences, which so far received little attention and remain underexploited. The successful commissioning within the past ten years of THEMIS, Hinode, STEREO and SDO spacecraft, in combination with matured analysis of data from earlier spacecraft (Wind, SOHO, ACE, Cluster, TRACE and RHESSI) makes it very timely to survey the breadth of observations giving evidence for MHD oscillatory processes in solar and space plasmas, and state-of-the-art theoretical modelling. The paper reviews several important topics, such as Alfv´enic resonances and mode conversion; MHD waveguides, such as the magnetotail, coronal loops, coronal streamers; mechanisms for periodicities produced in energy releases during substorms and solar flares, possibility of Alfv´enic resonators along open field lines; possible drivers of MHD waves; diagnostics of plasmas with MHD waves; interaction of MHD waves with partlyionised boundaries (ionosphere and chromosphere). The review is mainly oriented to specialists in magnetospheric physics and solar physics, but not familiar with specifics of the adjacent research fields

Post-Newtonian expansions for perfect fluids

We prove the existence of a large class of dynamical solutions to the Einstein-Euler equations that have a first post-Newtonian expansion. The results here are based on the elliptic-hyperbolic formulation of the Einstein-Euler equations used in \cite{Oli06}, which contains a singular parameter \ep = v_T/c, where $v_T$ is a characteristic velocity associated with the fluid and $c$ is the speed of light. As in \cite{Oli06}, energy estimates on weighted Sobolev spaces are used to analyze the behavior of solutions to the Einstein-Euler equations in the limit \ep\searrow 0, and to demonstrate the validity of the first post-Newtonian expansion as an approximation

Time-Independent Gravitational Fields

This article reviews, from a global point of view, rigorous results on time independent spacetimes. Throughout attention is confined to isolated bodies at rest or in uniform rotation in an otherwise empty universe. The discussion starts from first principles and is, as much as possible, self-contained.Comment: 47 pages, LaTeX, uses Springer cl2emult styl

Theorems on existence and global dynamics for the Einstein equations

This article is a guide to theorems on existence and global dynamics of solutions of the Einstein equations. It draws attention to open questions in the field. The local-in-time Cauchy problem, which is relatively well understood, is surveyed. Global results for solutions with various types of symmetry are discussed. A selection of results from Newtonian theory and special relativity that offer useful comparisons is presented. Treatments of global results in the case of small data and results on constructing spacetimes with prescribed singularity structure or late-time asymptotics are given. A conjectural picture of the asymptotic behaviour of general cosmological solutions of the Einstein equations is built up. Some miscellaneous topics connected with the main theme are collected in a separate section.Comment: Submitted to Living Reviews in Relativity, major update of Living Rev. Rel. 5 (2002)

Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse

BRAFΔβ3−αC^{Δβ3-αC} in-frame deletion mutants differ in their dimerization propensity, HSP90 dependence, and druggability

In-frame BRAF exon 12 deletions are increasingly identified in various tumor types. The resultant BRAF$^{Δβ3-αC}$ oncoproteins usually lack five amino acids in the β3-αC helix linker and sometimes contain de novo insertions. The dimerization status of BRAF$^{Δβ3-αC}$ oncoproteins, their precise pathomechanism, and their direct druggability by RAF inhibitors (RAFi) has been under debate. Here, we functionally characterize BRAF$^{ΔLNVTAP>F}$ and two novel mutants, BRAF$^{delinsFS}$ and BRAF$^{ΔLNVT>F}$, and compare them with other BRAF$^{Δβ3-αC}$ oncoproteins. We show that BRAF$^{Δβ3-αC}$ oncoproteins not only form stable homodimers and large multiprotein complexes but also require dimerization. Nevertheless, details matter as aromatic amino acids at the deletion junction of some BRAF$^{Δβ3-αC}$ oncoproteins, e.g., BRAF$^{ΔLNVTAP>F}$, increase their stability and dimerization propensity while conferring resistance to monomer-favoring RAFi such as dabrafenib or HSP 90/CDC37 inhibition. In contrast, dimer-favoring inhibitors such as naporafenib inhibit all BRAF$^{Δβ3-αC}$ mutants in cell lines and patient-derived organoids, suggesting that tumors driven by such oncoproteins are vulnerable to these compounds

Right Scaling for Right Pricing: A Case Study on Total Cost of Ownership Measurement for Cloud Migration

Cloud computing promises traditional enterprises and independent software vendors a myriad of advantages over on-premise installations including cost, operational and organizational efficiencies. The decision to migrate software configured for on-premise delivery to the cloud requires careful technical consideration and planning. In this chapter, we discuss the impact of right-scaling on the cost modelling for migration decision making and price setting of software for commercial resale. An integrated process is presented for measuring total cost of ownership, taking in to account IaaS/PaaS resource consumption based on forecast SaaS usage levels. The process is illustrated with a real world case study