AXL targeting reduces fibrosis development in experimental unilateral ureteral obstruction

The AXL receptor tyrosine kinase (RTK) is involved in partial epithelial-to-mesenchymal transition (EMT) and inflammation - both main promoters of renal fibrosis development. The study aim was to investigate the role of AXL inhibition in kidney fibrosis due to unilateral ureteral obstruction (UUO). Eight weeks old male C57BL/6 mice underwent UUO and were treated with oral AXL inhibitor bemcentinib (n = 22), Angiotensin-converting enzyme inhibitor (ACEI, n = 10), ACEI and bemcentinib (n = 10) or vehicle alone (n = 22). Mice were sacrificed after 7 or 15 days and kidney tissues were analyzed by immunohistochemistry (IHC), western blot, ELISA, Sirius Red (SR) staining, and hydroxyproline (Hyp) quantification. RNA was extracted from frozen kidney tissues and sequenced on an Illumina HiSeq4000 platform. After 15 days the ligated bemcentinib-treated kidneys showed less fibrosis compared to the ligated vehicle-treated kidneys in SR analyses and Hyp quantification. Reduced IHC staining for Vimentin (VIM) and alpha smooth muscle actin (alpha SMA), as well as reduced mRNA abundance of key regulators of fibrosis such as transforming growth factor (Tgf beta), matrix metalloproteinase 2 (Mmp2), Smad2, Smad4, myofibroblast activation (Aldh1a2, Crlf1), and EMT (Snai1,2, Twist), in ligated bemcentinib-treated kidneys was compatible with reduced (partial) EMT induction. Furthermore, less F4/80 positive cells, less activity of pathways related to the immune system and lower abundance of MCP1, MCP3, MCP5, and TARC in ligated bemcentinib-treated kidneys was compatible with reduction in inflammatory infiltrates by bemcentinib treatment. The AXL RTK pathway represents a promising target for pharmacologic therapy of kidney fibrosis.Peer reviewe

Influence of fast interstellar gas flow on dynamics of dust grains

The orbital evolution of a dust particle under the action of a fast interstellar gas flow is investigated. The secular time derivatives of Keplerian orbital elements and the radial, transversal, and normal components of the gas flow velocity vector at the pericentre of the particle's orbit are derived. The secular time derivatives of the semi-major axis, eccentricity, and of the radial, transversal, and normal components of the gas flow velocity vector at the pericentre of the particle's orbit constitute a system of equations that determines the evolution of the particle's orbit in space with respect to the gas flow velocity vector. This system of differential equations can be easily solved analytically. From the solution of the system we found the evolution of the Keplerian orbital elements in the special case when the orbital elements are determined with respect to a plane perpendicular to the gas flow velocity vector. Transformation of the Keplerian orbital elements determined for this special case into orbital elements determined with respect to an arbitrary oriented plane is presented. The orbital elements of the dust particle change periodically with a constant oscillation period or remain constant. Planar, perpendicular and stationary solutions are discussed. The applicability of this solution in the Solar system is also investigated. We consider icy particles with radii from 1 to 10 micrometers. The presented solution is valid for these particles in orbits with semi-major axes from 200 to 3000 AU and eccentricities smaller than 0.8, approximately. The oscillation periods for these orbits range from 10^5 to 2 x 10^6 years, approximately.Comment: 22 pages, 3 figures; Accepted for publication in Celestial Mechanics and Dynamical Astronom

ECCD-induced sawtooth crashes at W7-X

The optimised superconducting stellarator W7-X generates its rotational transform by means of external coils, therefore no toroidal current is necessary for plasma confinement. Electron cyclotron current drive experiments were conducted for strikeline control and safe divertor operation. During current drive experiments periodic and repetitive crashes of the central electron temperature, similar to sawtooth crashes in tokamaks, were detected. Measurements from soft x-ray tomography and electron cyclotron emission show that the crashes are preceded by weak oscillating precursors and a displacement of the plasma core, consistent with a (m, n)=(1, 1) mode. The displacement occurs within 100μs, followed by expulsion and redistribution of the core into the external part of the plasma. Two types of crashes, with different frequencies and amplitudes are detected in the experimental program. For these non-stationary parameters a strong dependence on the toroidal current is found. A 1-D heuristic model for current diffusion is proposed as a first step to explain the characteristic crash time. Initial results show that the modelled current diffusion timescale is consistent with the initial crash frequency and that the toroidal current rise shifts the position where the instability is triggered, resulting in larger crash amplitudes

Wholesale pricing in a small open economy

This paper addresses the empirical analysis of wholesale profit margins using data of the Dutch wholesale sector, 1986. At the heart of the analysis is the typical nature of wholesale production: wholesalers do not produce a tangible product, but offer a service capacity. This has an immediate impact on the identification, interprelation and measurement of determinants of profit variations. A model is set up to explain variations in wholesale profit margins, which is inspired by two widely applied approaches to industry pricing: the behavioural mark-up model and the marginalist price-cost model

Solar parameters for modeling interplanetary background

The goal of the Fully Online Datacenter of Ultraviolet Emissions (FONDUE) Working Team of the International Space Science Institute in Bern, Switzerland, was to establish a common calibration of various UV and EUV heliospheric observations, both spectroscopic and photometric. Realization of this goal required an up-to-date model of spatial distribution of neutral interstellar hydrogen in the heliosphere, and to that end, a credible model of the radiation pressure and ionization processes was needed. This chapter describes the solar factors shaping the distribution of neutral interstellar H in the heliosphere. Presented are the solar Lyman-alpha flux and the solar Lyman-alpha resonant radiation pressure force acting on neutral H atoms in the heliosphere, solar EUV radiation and the photoionization of heliospheric hydrogen, and their evolution in time and the still hypothetical variation with heliolatitude. Further, solar wind and its evolution with solar activity is presented in the context of the charge exchange ionization of heliospheric hydrogen, and in the context of dynamic pressure variations. Also the electron ionization and its variation with time, heliolatitude, and solar distance is presented. After a review of all of those topics, we present an interim model of solar wind and the other solar factors based on up-to-date in situ and remote sensing observations of solar wind. Results of this effort will further be utilised to improve on the model of solar wind evolution, which will be an invaluable asset in all heliospheric measurements, including, among others, the observations of Energetic Neutral Atoms by the Interstellar Boundary Explorer (IBEX).Comment: Chapter 2 in the planned "Cross-Calibration of Past and Present Far UV Spectra of Solar System Objects and the Heliosphere", ISSI Scientific Report No 12, ed. R.M. Bonnet, E. Quemerais, M. Snow, Springe

Forward modeling of collective Thomson scattering for Wendelstein 7-X plasmas: Electrostatic approximation

In this paper, we present a method for numerical computation of collective Thomson scattering (CTS). We developed a forward model, eCTS, in the electrostatic approximation and benchmarked it against a full electromagnetic model. Differences between the electrostatic and the electromagnetic models are discussed. The sensitivity of the results to the ion temperature and the plasma composition is demonstrated. We integrated the model into the Bayesian data analysis framework Minerva and used it for the analysis of noisy synthetic data sets produced by a full electromagnetic model. It is shown that eCTS can be used for the inference of the bulk ion temperature. The model has been used to infer the bulk ion temperature from the first CTS measurements on Wendelstein 7-X

Towards a new image processing system at Wendelstein 7-X: From spatial calibration to characterization of thermal events

Wendelstein 7-X (W7-X) is the most advanced fusion experiment in the stellarator line and is aimed at proving that the stellarator concept is suitable for a fusion reactor. One of the most important issues for fusion reactors is the monitoring of plasma facing components when exposed to very high heat loads, through the use of visible and infrared (IR) cameras. In this paper, a new image processing system for the analysis of the strike lines on the inboard limiters from the first W7-X experimental campaign is presented. This system builds a model of the IR cameras through the use of spatial calibration techniques, helping to characterize the strike lines by using the information given by real spatial coordinates of each pixel. The characterization of the strike lines is made in terms of position, size, and shape, after projecting the camera image in a 2D grid which tries to preserve the curvilinear surface distances between points. The description of the strike-line shape is made by means of the Fourier Descriptors