Up-down symmetry of the turbulent transport of toroidal angular momentum in tokamaks

Two symmetries of the local nonlinear delta-f gyrokinetic system of equations in tokamaks in the high flow regime are presented. The turbulent transport of toroidal angular momentum changes sign under an up-down reflection of the tokamak and a sign change of both the rotation and the rotation shear. Thus, the turbulent transport of toroidal angular momentum must vanish for up-down symmetric tokamaks in the absence of both rotation and rotation shear. This has important implications for the modeling of spontaneous rotation.Comment: 15 pages, 2 figure

Toroidal momentum transport in a tokamak caused by symmetry breaking parallel derivatives

A new mechanism for toroidal momentum transport in a tokamak is investigated using the gyro-kinetic model. First, an analytic model is developed through the use of the ballooning transform. The terms that generate the momentum transport are then connected with the poloidal derivative of the ballooning envelope, which are one order smaller in the normalised Larmor radius, compared with the derivative of the eikonal. The mechanism, therefore, does not introduce an inhomogeneity in the radial direction, in contrast with the effect of profile shearing. Numerical simulations of the linear ion temperature gradient mode with adiabatic electrons, retaining the finite rho* effects in the ExB velocity, the drift, and the gyro-average, are presented. The momentum flux is found to be linear in the normalised Larmor radius (\rho*) but is, nevertheless, generating a sizeable counter-current rotation. The total momentum flux scales linear with the aspect ratio of the considered magnetic surface, and increases with increasing magnetic shear, safety factor, and density and temperature gradients

Improving virtual screening of G protein-coupled receptors via ligand-directed modeling

G protein-coupled receptors (GPCRs) play crucial roles in cell physiology and pathophysiology. There is increasing interest in using structural information for virtual screening (VS) of libraries and for structure-based drug design to identify novel agonist or antagonist leads. However, the sparse availability of experimentally determined GPCR/ligand complex structures with diverse ligands impedes the application of structure-based drug design (SBDD) programs directed to identifying new molecules with a select pharmacology. In this study, we apply ligand-directed modeling (LDM) to available GPCR X-ray structures to improve VS performance and selectivity towards molecules of specific pharmacological profile. The described method refines a GPCR binding pocket conformation using a single known ligand for that GPCR. The LDM method is a computationally efficient, iterative workflow consisting of protein sampling and ligand docking. We developed an extensive benchmark comparing LDM-refined binding pockets to GPCR X-ray crystal structures across seven different GPCRs bound to a range of ligands of different chemotypes and pharmacological profiles. LDM-refined models showed improvement in VS performance over origin X-ray crystal structures in 21 out of 24 cases. In all cases, the LDM-refined models had superior performance in enriching for the chemotype of the refinement ligand. This likely contributes to the LDM success in all cases of inhibitor-bound to agonist-bound binding pocket refinement, a key task for GPCR SBDD programs. Indeed, agonist ligands are required for a plethora of GPCRs for therapeutic intervention, however GPCR X-ray structures are mostly restricted to their inactive inhibitor-bound state

Action to protect the independence and integrity of global health research

Storeng KT, Abimbola S, Balabanova D, et al. Action to protect the independence and integrity of global health research. BMJ GLOBAL HEALTH. 2019;4(3): e001746

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Vessel orientation-dependent sensitivity of optoacoustic imaging using a linear array transducer

For clinical optoacoustic imaging, linear probes are preferably used because they allow versatile imaging of the human body with real-time display and free-hand probe guidance. The two-dimensional (2-D) optoacoustic image obtained with this type of probe is generally interpreted as a 2-D cross-section of the tissue just as is common in echo ultrasound. We demonstrate in three-dimensional simulations, phantom experiments, and in vivo mouse experiments that for vascular imaging this interpretation is often inaccurate. The cylindrical blood vessels emit anisotropic acoustic transients, which can be sensitively detected only if the direction of acoustic radiation coincides with the probe aperture. Our results reveal for this reason that the signal amplitude of different blood vessels may differ even if the vessels have the same diameter and initial pressure distribution but different orientation relative to the imaging plane. This has important implications for the image interpretation, for the probe guidance technique, and especially in cases when a quantitative reconstruction of the optical tissue properties is required

Global nonlinear electromagnetic simulations of tokamak turbulence

The particle-in-cell code ORB5 is a global gyrokinetic turbulence simulation code in tokamak geometry. It has been developed at CRPP, Lausanne, Switzerland, with major contributions from IPP, Garching, Germany, and IPP, Greifswald, Germany, under a long-standing collaboration. The code ORB5 solves the gyrokinetic equations in the whole plasma core, including the magnetic axis. A field-aligned filtering procedure and sophisticated noise-control and heating operators allow for accurate simulations. Recently, the code ORB5 has been extended to include self-consistent perpendicular magnetic field perturbations. The inclusion of magnetic perturbations allows for a comprehensive study of finite beta effects on microinstability. In this paper, we present the first linear and nonlinear code results concerning electromagnetic effects on tokamak microinstabilities