dráma 4 felvonásban - írta Eugéne Brieux - fordította Zigány Árpád - rendező Kemény Lajos

Városi Szinház. Debreczen, 1913 február 15 -én szombaton: K. Hegyesy Mari és Beregi Oszkár a budapesti nemzeti szinház művészeinek együttes felléptével.Debreceni Egyetem Egyetemi és Nemzeti Könyvtá

Systematic evaluation of particle loss during handling in the percutaneous transluminal angioplasty for eight different drug-coated balloons

Paclitaxel drug coated balloons (DCBs) should provide optimal drug transfer exclusively to the target tissue. The aim of this study was to evaluate the particle loss by handling during angioplasty. A robotic arm was developed for systematic and reproducible drug abrasion experiments. The contact force on eight different commercially available DCB types was gradually increased, and high-resolution microscopic images of the deflated and inflated balloons were recorded. Three types of DCBs were classified: no abrasion of the drug in both statuses (deflated and inflated), significant abrasion only in the inflated status, and significant abrasion in both statuses. Quantitative measurements via image processing confirmed the qualitative classification and showed changes of the drug area between 2.25 and 45.73% (13.28 ± 14.29%) in the deflated status, and between 1.66 and 40.41% (21.43 ± 16.48%) in the inflated status. The structures and compositions of the DCBs are different, some are significantly more susceptible to drug loss. Particle loss by handling during angioplasty leads to different paclitaxel doses in the target regions for same DCB types. Susceptibility to involuntary drug loss may cause side effects, such as varying effective paclitaxel doses, which may explain variations in studies regarding the therapeutic outcome

Levodopa‐induced dyskinesia are mediated by cortical gamma oscillations in experimental Parkinsonism

Background Levodopa is the most efficacious drug in the symptomatic therapy of motor symptoms in Parkinson's disease (PD); however, long‐term treatment is often complicated by troublesome levodopa‐induced dyskinesia (LID). Recent evidence suggests that LID might be related to increased cortical gamma oscillations. Objective The objective of this study was to test the hypothesis that cortical high‐gamma network activity relates to LID in the 6‐hydroxydopamine model and to identify new biomarkers for adaptive deep brain stimulation (DBS) therapy in PD. Methods We recorded and analyzed primary motor cortex (M1) electrocorticogram data and motor behavior in freely moving 6‐OHDA lesioned rats before and during a daily treatment with levodopa for 3 weeks. The results were correlated with the abnormal involuntary movement score (AIMS) and used for generalized linear modeling (GLM). Results Levodopa reverted motor impairment, suppressed beta activity, and, with repeated administration, led to a progressive enhancement of LID. Concurrently, we observed a highly significant stepwise amplitude increase in finely tuned gamma (FTG) activity and gamma centroid frequency. Whereas AIMS and FTG reached their maximum after the 4th injection and remained on a stable plateau thereafter, the centroid frequency of the FTG power continued to increase thereafter. Among the analyzed gamma activity parameters, the fraction of longest gamma bursts showed the strongest correlation with AIMS. Using a GLM, it was possible to accurately predict AIMS from cortical recordings. Conclusions FTG activity is tightly linked to LID and should be studied as a biomarker for adaptive DBS

The Christiansen Effect in Saturn's narrow dusty rings and the spectral identification of clumps in the F ring

Stellar occultations by Saturn's rings observed with the Visual and Infrared Mapping Spectrometer (VIMS) onboard the Cassini spacecraft reveal that dusty features such as the F ring and the ringlets in the Encke and the Laplace Gaps have distinctive infrared transmission spectra. These spectra show a narrow optical depth minimum at wavelengths around 2.87 microns. This minimum is likely due to the Christiansen Effect, a reduction in the extinction of small particles when their (complex) refractive index is close to that of the surrounding medium. Simple Mie-scattering models demonstrate that the strength of this opacity dip is sensitive to the size distribution of particles between 1 and 100 microns across. Furthermore, the spatial resolution of the occultation data is sufficient to reveal variations in the transmission spectra within and among these rings. For example, in both the Encke Gap ringlets and F ring, the opacity dip weakens with increasing local optical depth, which is consistent with the larger particles being concentrated near the cores of these rings. The strength of the opacity dip varies most dramatically within the F ring; certain compact regions of enhanced optical depth lack an opacity dip and therefore appear to have a greatly reduced fraction of grains in the few-micron size range.Such spectrally-identifiable structures probably represent a subset of the compact optically-thick clumps observed by other Cassini instruments. These variations in the ring's particle size distribution can provide new insights into the processes of grain aggregation, disruption and transport within dusty rings. For example, the unusual spectral properties of the F-ring clumps could perhaps be ascribed to small grains adhering onto the surface of larger particles in regions of anomalously low velocity dispersion.Comment: 42 pages, 15 figures, accepted for publication in Icarus. A few small typographical errors fixed to match correction in proof

Characterisation of the passive permeability barrier of nuclear pore complexes

Nuclear pore complexes (NPCs) restrict uncontrolled nucleocytoplasmic fluxes of inert macromolecules but permit facilitated translocation of nuclear transport receptors and their cargo complexes. We probed the passive barrier of NPCs and observed sieve-like properties with a dominating mesh or channel radius of 2.6 nm, which is narrower than proposed earlier. A small fraction of diffusion channels has a wider opening, explaining the very slow passage of larger molecules. The observed dominant passive diameter approximates the distance of adjacent hydrophobic clusters of FG repeats, supporting the model that the barrier is made of FG repeat domains cross-linked with a spacing of an FG repeat unit length. Wheat germ agglutinin and the dominant-negative importin β45-462 fragment were previously regarded as selective inhibitors of facilitated NPC passage. We now observed that they do not distinguish between the passive and the facilitated mode. Instead, their inhibitory effect correlates with the size of the NPC-passing molecule. They have little effect on small species, inhibit the passage of green fluorescent protein-sized objects >10-fold and virtually block the translocation of larger ones. This suggests that passive and facilitated NPC passage proceed through one and the same permeability barrier

Neutralization of SARS-CoV-2 by highly potent, hyperthermostable, and mutation-tolerant nanobodies

Monoclonal anti-SARS-CoV-2 immunoglobulins represent a treatment option for COVID-19. However, their production in mammalian cells is not scalable to meet the global demand. Single-domain (VHH) antibodies (also called nanobodies) provide an alternative suitable for microbial production. Using alpaca immune libraries against the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein, we isolated 45 infection-blocking VHH antibodies. These include nanobodies that can withstand 95°C. The most effective VHH antibody neutralizes SARS-CoV-2 at 17–50 pM concentration (0.2–0.7 µg per liter), binds the open and closed states of the Spike, and shows a tight RBD interaction in the X-ray and cryo-EM structures. The best VHH trimers neutralize even at 40 ng per liter. We constructed nanobody tandems and identified nanobody monomers that tolerate the K417N/T, E484K, N501Y, and L452R immune-escape mutations found in the Alpha, Beta, Gamma, Epsilon, Iota, and Delta/Kappa lineages. We also demonstrate neutralization of the Beta strain at low-picomolar VHH concentrations. We further discovered VHH antibodies that enforce native folding of the RBD in the E. coli cytosol, where its folding normally fails. Such “fold-promoting” nanobodies may allow for simplified production of vaccines and their adaptation to viral escape-mutations

First detection of a diamagnetic cavity at comet 67P/Churyumov-Gerasimenko

International audienceContext: The Rosetta magnetometer RPC-MAG has been exploring the plasma environment of comet 67P/Churyumov-Gerasimenko since August 2014. The first months were dominated by low-frequency waves which evolved into more complex features. However, at the end of July 2015, close to perihelion, the magnetometer detected a region that did not contain any magnetic field at all.Aims: These signatures match the appearance of a diamagnetic cavity as was observed at comet 1P/Halley in 1986. The cavity here is more extended than previously predicted by models and features unusual magnetic field configurations, which need to be explainedMethods: The onboard magnetometer data were analyzed in detail and used to estimate the outgassing rate. A minimum variance analysis was used to determine boundary normals.Results. Our analysis of the data acquired by the Rosetta Plasma Consortium instrumentation confirms the existence of a diamagnetic cavity. The size is larger than predicted by simulations, however. One possible explanation are instabilities that are propagating along the cavity boundary and possibly a low magnetic pressure in the solar wind. This conclusion is supported by a change in sign of the Sun-pointing component of the magnetic field. Evidence also indicates that the cavity boundary is moving with variable velocities ranging from 230−500 m/s