Shear wave splitting and mantle flow beneath LA RISTRA

Shear-wave splitting parameters (fast polarization direction and delay time) are determined using data from LA RISTRA (Colorado pLAteau RIo Grande Rift/Great Plains Seismic TRAnsect), a deployment of broadband seismometers extending from the Great Plains, across the Rio Grande Rift and the Jemez Lineament, to the Colorado Plateau. Results show that the fast polarization directions are sub-parallel to North American absolute plate motion. The largest deviations from the plate motion are observed within the western edge of the Great Plains and in the interior of the Colorado Plateau where lithospheric anisotropy may be significant. Delay times range from 0.8 to 1.8 seconds with an average value of 1.4 seconds; the largest values are along the Jemez Lineament and the Rio Grande Rift which are underlain by an uppermost mantle low velocity zone extending to depths of ∼200 km. The anisotropy beneath the central part of LA RISTRA shows a remarkably consistent pattern with a mean fast direction of 40° ± 6°. Seismic anisotropy can be explained by differential horizontal motion between the North American lithosphere and westerly to southwesterly flow of the asthenospheric mantle. The approximately N-S fast direction found beneath western Texas is similar to that observed beneath the southern rift and may reflect a different dynamic regime

timueh/PolyChaos.jl: v0.1.2

A Julia package to construct orthogonal polynomials, their quadrature rules, and use it with polynomial chaos expansions

Acoustic modeling of hoarseness

Wiechmann J, Rautenberg F, Wagner P, Häb-Umbach R. Acoustic modeling of hoarseness. In: Pistor TR, Steiner C, Tomascheck F, Leemann A, eds. Book of Abstracts der 19. Tagung Phonetik und Phonologie im deutschsprachigen Raum. Bern: Bern Open Publishing; 2023

Eltanexor Effectively Reduces Viability of Glioblastoma and Glioblastoma Stem-Like Cells at Nano-Molar Concentrations and Sensitizes to Radiotherapy and Temozolomide

Current standard adjuvant therapy of glioblastoma multiforme (GBM) using temozolomide (TMZ) frequently fails due to therapy resistance. Thus, novel therapeutic approaches are highly demanded. We tested the therapeutic efficacy of the second-generation XPO1 inhibitor Eltanexor using assays for cell viability and apoptosis in GBM cell lines and GBM stem-like cells. For most GBM-derived cells, IC50 concentrations for Eltanexor were below 100 nM. In correlation with reduced cell viability, apoptosis rates were significantly increased. GBM stem-like cells presented a combinatorial effect of Eltanexor with TMZ on cell viability. Furthermore, pretreatment of GBM cell lines with Eltanexor significantly enhanced radiosensitivity in vitro. To explore the mechanism of apoptosis induction by Eltanexor, TP53-dependent genes were analyzed at the mRNA and protein level. Eltanexor caused induction of TP53-related genes, TP53i3, PUMA, CDKN1A, and PML on both mRNA and protein level. Immunofluorescence of GBM cell lines treated with Eltanexor revealed a strong accumulation of CDKN1A, and, to a lesser extent, of p53 and Tp53i3 in cell nuclei as a plausible mechanism for Eltanexor-induced apoptosis. From these data, we conclude that monotherapy with Eltanexor effectively induces apoptosis in GBM cells and can be combined with current adjuvant therapies to provide a more effective therapy of GBM

Indacaterol/Glycopyrronium improves pulmonary ventilation and ventilation inhomogeneity in the CLAIM Study

Background: Ventilation of the lungs is disturbed in COPD. Bronchodilator treatment reduces airway obstruction and improves airflow in the lung. Analysis of lung ventilation might help to further characterize COPD patients and assess treatment effects. Objectives: The objective was to analyze treatment effects of indacaterol/glycopyrronium (IND/GLY) on regional lung ventilation. Methods: CLAIM was a randomized, double-blind, single-center, placebo-controlled, 2 period cross-over trial. 62 hyperinflated COPD patients were enrolled to receive IND/GLY (110/50 μg q.d.) for 14 days followed by placebo or vice versa. Regional lung ventilation was measured under free breathing conditions in three coronal slices and in left and right sagittal slices using phase-resolved functional lung (PREFUL)-MRI. Results: Analysis of coronal lung slices showed that treatment with IND/GLY increased total fractional ventilation (FV) in the lung by 12.4% vs. placebo (relative LS Mean difference, p=0.0114) at day 14. Increase in total FV was associated with a reduction of hypoventilated areas (volume defect percentage) by 16.6% (p=0.0002) and an increase in homogeneity of lung ventilation by 12.4% (p<0.0001) vs. placebo, measured as reduction of the variation coefficient of FV. Similar results were obtained for sagittal slices, thereby supporting the validity of these results for the entire lung. Conclusion: IND/GLY improved lung ventilation in hyperinflated COPD patients. Importantly, this was associated with a reduction of hypoventilated areas and increased homogeneity. Improved regional lung ventilation might contribute to the reduction in dyspnea reported earlier for the CLAIM study