Involvement of cardiac fibroblasts in anthracycline-induced cardiotoxicity

A momentous side-effect of the treatment with anthracyclines like doxorubicin (DOX) is the cumulative, dose-dependent damage of the heart. The chronic anthracycline-induced cardiotoxicity (ACT) leads to the development of symptomatic heart failure in 6 to 9 % of all patients treated and is greatly impairing patient outcome. The search for preventive and therapeutic strategies has yielded little success so far as molecular mechanisms are not fully understood. The production of reactive oxygen species (ROS), mitochondrial dysfunction and topoisomerase 2β inhibition have been proposed as parts of the complex and multifactorial disease model. The aim of this study was to investigate the potential role of cardiac fibroblasts in ACT development in terms of ROS production and NAPDH oxidase subunit expression. Human cardiac fibroblasts (cFB) were isolated from fresh cardiac tissue after heart transplantation from an ACT and a dilative cardiomyopathy (DCM) patient. Isolated cFBs show morphological characteristics, high proliferation capacity and expression of typical cardiac fibroblast markers as periostin, transcription factor 21 and α-smooth muscle actin in qRT-PCR and immunocytochemistry experiments. To analyze the acute reaction to anthracycline treatment, cFBs were exposed to 0.1 or 0.25 μM DOX for 24 hours and analyzed regarding the expression of NADPH oxidase subunits on mRNA level via qRT-PCR and on protein level via Western blot. Subunits RAC2 and NCF4 were expressed significantly more highly in cardiac fibroblasts compared to skin fibroblasts. As an immediate response to DOX treatment, tendencies of expression changes were found for NOX2, NOX4, RAC2 and NCF4. Additionally, the expression of NADPH oxidase subunits in tissue of chronic heart failure patients was studied showing that expression levels for the subunits differed between ACT patients, DCM patients and healthy controls. DOX-dependent production of ROS in cFBs was assessed using the Amplex Red reagent for hydrogen peroxide and DHE-HPLC for superoxide. DOX concentrations of 0.1 to 0.25 μM DOX caused a dose-dependent significant increase of ROS. Also, hydrogen peroxide levels were higher in cardiac fibroblasts compared to skin fibroblasts and NADPH-contributable superoxide production was only measurable when the cells were triggered with DOX treatment. In conclusion, this study suggests that cardiac fibroblasts contribute to ACT development and not only to the manifestation of the fibrotic phenotype following cardiomyocyte apoptosis. Also, the NADPH oxidase appears to be a promising target for further research based on the expression changes and differences found in this study.2021-11-0

Brief communication: Unravelling the composition and microstructure of a permafrost core using X-ray computed tomography

The microstructure of permafrost ground contains clues to its formation and hence its preconditioning to future change. We applied X-ray computed microtomography (CT) to obtain high-resolution data (Δx=50 µm) of the composition of a 164 cm long permafrost core drilled in a Yedoma upland in north-eastern Siberia. The CT analysis allowed the microstructures to be directly mapped and volumetric contents of excess ice, gas inclusions, and two distinct sediment types to be quantified. Using laboratory measurements of coarsely resolved core samples, we statistically estimated the composition of the sediment types and used it to indirectly quantify volumetric contents of pore ice, organic matter, and mineral material along the core. We conclude that CT is a promising method for obtaining physical properties of permafrost cores which opens novel research potentials

Low Q^2 Jet Production at HERA and Virtual Photon Structure

The transition between photoproduction and deep-inelastic scattering is investigated in jet production at the HERA ep collider, using data collected by the H1 experiment. Measurements of the differential inclusive jet cross-sections dsigep/dEt* and dsigmep/deta*, where Et* and eta* are the transverse energy and the pseudorapidity of the jets in the virtual photon-proton centre of mass frame, are presented for 0 < Q2 < 49 GeV2 and 0.3 < y < 0.6. The interpretation of the results in terms of the structure of the virtual photon is discussed. The data are best described by QCD calculations which include a partonic structure of the virtual photon that evolves with Q2.Comment: 20 pages, 5 Figure

Hadron Production in Diffractive Deep-Inelastic Scattering

Characteristics of hadron production in diffractive deep-inelastic positron-proton scattering are studied using data collected in 1994 by the H1 experiment at HERA. The following distributions are measured in the centre-of-mass frame of the photon dissociation system: the hadronic energy flow, the Feynman-x (x_F) variable for charged particles, the squared transverse momentum of charged particles (p_T^{*2}), and the mean p_T^{*2} as a function of x_F. These distributions are compared with results in the gamma^* p centre-of-mass frame from inclusive deep-inelastic scattering in the fixed-target experiment EMC, and also with the predictions of several Monte Carlo calculations. The data are consistent with a picture in which the partonic structure of the diffractive exchange is dominated at low Q^2 by hard gluons.Comment: 16 pages, 6 figures, submitted to Phys. Lett.

Measurement of D* Meson Cross Sections at HERA and Determination of the Gluon Density in the Proton using NLO QCD

With the H1 detector at the ep collider HERA, D* meson production cross sections have been measured in deep inelastic scattering with four-momentum transfers Q^2>2 GeV2 and in photoproduction at energies around W(gamma p)~ 88 GeV and 194 GeV. Next-to-Leading Order QCD calculations are found to describe the differential cross sections within theoretical and experimental uncertainties. Using these calculations, the NLO gluon momentum distribution in the proton, x_g g(x_g), has been extracted in the momentum fraction range 7.5x10^{-4}< x_g <4x10^{-2} at average scales mu^2 =25 to 50 GeV2. The gluon momentum fraction x_g has been obtained from the measured kinematics of the scattered electron and the D* meson in the final state. The results compare well with the gluon distribution obtained from the analysis of scaling violations of the proton structure function F_2.Comment: 27 pages, 9 figures, 2 tables, submitted to Nucl. Phys.

A Search for Selectrons and Squarks at HERA

Data from electron-proton collisions at a center-of-mass energy of 300 GeV are used for a search for selectrons and squarks within the framework of the minimal supersymmetric model. The decays of selectrons and squarks into the lightest supersymmetric particle lead to final states with an electron and hadrons accompanied by large missing energy and transverse momentum. No signal is found and new bounds on the existence of these particles are derived. At 95% confidence level the excluded region extends to 65 GeV for selectron and squark masses, and to 40 GeV for the mass of the lightest supersymmetric particle.Comment: 13 pages, latex, 6 Figure

A Measurement of the Proton Structure Function F ⁣2(x,Q2)F_{\!2}(x,Q^2)

A measurement of the proton structure function $F_{\!2}(x,Q^2)$ is reported for momentum transfer squared $Q^2$ between 4.5 $GeV^2$ and 1600 $GeV^2$ and for Bjorken $x$ between $1.8\cdot10^{-4}$ and 0.13 using data collected by the HERA experiment H1 in 1993. It is observed that $F_{\!2}$ increases significantly with decreasing $x$, confirming our previous measurement made with one tenth of the data available in this analysis. The $Q^2$ dependence is approximately logarithmic over the full kinematic range covered. The subsample of deep inelastic events with a large pseudo-rapidity gap in the hadronic energy flow close to the proton remnant is used to measure the "diffractive" contribution to $F_{\!2}$.Comment: 32 pages, ps, appended as compressed, uuencoded fil

Applying Computed Tomography (CT) scanning for segmentation of permafrost constituents in drill cores

Computed X-ray Tomography is a non-destructive technique that allows three-dimensional imaging of soil samples' internal structures, determined by variations in their density and atomic composition. This study's objective was to develop an image processing workflow for the quantitative analysis of ice cores using high-resolution CT in order to determine the volume fraction and vertical distribution of ice, mineral, gas, and organic matter in permafrost cores. We analyzed a 155 cm permafrost core taken from a Yedoma permafrost upland on Kurungnakh Island in the Lena River Delta (northeast Siberia). The obtained results were evaluated and compared with the results of detailed, but sample-destructive laboratory analysis. The frozen permafrost core was subjected to a computerized X-ray imaging procedure with a resolution of 50 micrometers. As a result, we obtained 31000 images. Noise in the raw images is removed with a non-local means denoising filter. We chose multilevel thresholding method for the image segmentation step. Threshold values were determined based on the histograms of the images. We measured the volumetric ice content (VIC) using Java-based image processing software (ImageJ). In addition, the vertical profiles were analyzed in 1-2cm intervals. We received bulk densities and VIC by freeze-drying and standard laboratory analysis. From the top of the core and until roughly 86 cm, it mainly consists of ice and organic, with an average of 67% and 30% results, respectively. The rest of the volume is divided almost equally between air and mineral parts. Below 86 cm, it consists almost entirely of pure ice. The ice content constitutes around 97% of the composition, and air rises to roughly 3%, while mineral and organic are almost equal to zero. The difference between VIC derived through CT scan and laboratory-derived VIC lies within the range of -37% to 25%. However, the vast majority of values lie within the range of -10% to 10%. This image processing technique to quantify VIC provides a non-destructive analog to traditional laboratory analysis that could help increasing the vertical resolution for quantifying mineral, ice, gas, and organic components in permafrost cores as well as enhance the volumetric estimate