Fully in situ Nb/InAs-nanowire Josephson junctions by selective-area growth and shadow evaporation

Josephson junctions based on InAs semiconducting nanowires and Nb superconducting electrodes are fabricated in situ by a special shadow evaporation scheme for the superconductor electrode. Compared to other metallic superconductors such as Al, Nb has the advantage of a larger superconducting gap which allows operation at higher temperatures and magnetic fields. Our junctions are fabricated by shadow evaporation of Nb on pairs of InAs nanowires grown selectively on two adjacent tilted Si (111) facets and crossing each other at a small distance. The upper wire relative to the deposition source acts as a shadow mask determining the gap of the superconducting electrodes on the lower nanowire. Electron microscopy measurements show that the fully in situ fabrication method gives a clean InAs/Nb interface. A clear Josephson supercurrent is observed in the current–voltage characteristics, which can be controlled by a bottom gate. The large excess current indicates a high junction transparency. Under microwave radiation, pronounced integer Shapiro steps are observed suggesting a sinusoidal current–phase relation. Owing to the large critical field of Nb, the Josephson supercurrent can be maintained to magnetic fields exceeding 1 T. Our results show that in situ prepared Nb/InAs nanowire contacts are very interesting candidates for superconducting quantum circuits requiring large magnetic fields

Identification of Novel Functional Inhibitors of Acid Sphingomyelinase

We describe a hitherto unknown feature for 27 small drug-like molecules, namely functional inhibition of acid sphingomyelinase (ASM). These entities named FIASMAs (Functional Inhibitors of Acid SphingoMyelinAse), therefore, can be potentially used to treat diseases associated with enhanced activity of ASM, such as Alzheimer's disease, major depression, radiation- and chemotherapy-induced apoptosis and endotoxic shock syndrome. Residual activity of ASM measured in the presence of 10 µM drug concentration shows a bimodal distribution; thus the tested drugs can be classified into two groups with lower and higher inhibitory activity. All FIASMAs share distinct physicochemical properties in showing lipophilic and weakly basic properties. Hierarchical clustering of Tanimoto coefficients revealed that FIASMAs occur among drugs of various chemical scaffolds. Moreover, FIASMAs more frequently violate Lipinski's Rule-of-Five than compounds without effect on ASM. Inhibition of ASM appears to be associated with good permeability across the blood-brain barrier. In the present investigation, we developed a novel structure-property-activity relationship by using a random forest-based binary classification learner. Virtual screening revealed that only six out of 768 (0.78%) compounds of natural products functionally inhibit ASM, whereas this inhibitory activity occurs in 135 out of 2028 (6.66%) drugs licensed for medical use in humans

SAKK 16/14: CD8 T Cell Positioning Correlates with Survival in Stage IIIA (N2) NSCLC After Neoadjuvant Immunotherapy

Spatial distribution of immune cells within the tumor immune microenvironment (TIME) influences response to immunotherapy in many malignancies, but its role in neoadjuvant immunotherapy in non-small cell lung cancer (NSCLC) is not clearly established. To address this knowledge gap, we performed digital pathology analysis of tumor tissue obtained from patients with stage IIIA(N2) NSCLC undergoing neoadjuvant chemotherapy with three cycles of cisplatin/docetaxel followed by treatment with the PD-L1 antibody durvalumab in the single-arm phase II trial SAKK 16/14. Methods Formalin-fixed paraffin-embedded tissue specimens of 21 initial biopsies (IB) and 38 resection specimens (RES) were obtained from patients enrolled in the trial SAKK 16/14. Tissue was immunostained for CD3, CD8, CD20 and FoxP3. Digitalized slides were annotated for invasive cancer. A machine-learning classifier was trained to localize and quantify marker-positive immune cell densities within the epithelial and stromal compartments. Also, the TIME for each specimen was classified as excluded Results The infiltration densities of CD3 T cells, CD8 T cells, CD20 B cells and Foxp3 T cells in IB (Fig. 1A) and RES (Fig. 1B) were comparable in hot and cold tumors. Stratification of tumors based on their immune cell positioning (excluded or inflamed phenotype) in the IB strongly correlated with EFS (p=0.008, Fig. 2A). This association was driven by CD8 T cell infiltration in the tumor (Fig. 2B), but not for the stromal compartment (Fig. 2C) or total T cell content (Fig. 2D) as assessed by digital Conclusions Immune phenotyping of the tumor and spatial distribution of CD8 T cells correlates with EFS in the SAKK16/14 cohort

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Der Artikel gibt einen Überblick über die Arbeiten im SFB 532 in den Teilprojekten B1-B3 Textil und im Teilprojekt E1 Produktionstechnik. Es werden Garnherstellungsverfahren erklärt und produzierte Garnvarianten gezeigt. Es erfolgt die Beschreibung der Maschinenentwicklungen im Bereich der 2D- und 3D Textilien. Durch die Ermittlung der mechanischen Kennwerte können Vergleiche zwischen Rovings, Garnen und Textilien durchgeführt werden. Für den Bereich der Produktionstechnik wird ein Konzept für eine kontinuierlich arbeitende Anlage zur Herstellung textilbewehrter Betonelemente