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The metal-rich phosphide TaCrP forms from the elements by step-wise solid state reaction in an alumina crucible (maximum annealing temperature 1180 K). TaCrP is trimorphic. The structural data of the hexagonal ZrNiAl high-temperature phase (space group P¯62m) was deduced from a Rietveld refinement. At room temperature TaCrP crystallizes with the TiNiSi type (Pnma, a = 623.86(5), b = 349.12(3), c = 736.78(6) pm, wR = 0.0419, 401 F2 values, 20 variables) and shows a Peierls type transition below ca. 280 K to the monoclinic low-temperature modification (P121/c1, a = 630.09(3), b = 740.3(4), c = 928.94(4) pm, β = 132.589(5)°, wR = 0.0580, 1378 F2 values, 57 variables). The latter phase transition is driven by pairwise Cr–Cr bond formation out of an equidistant chain in o-TaCrP. The phase transition was monitored via different analytical tools: differential scanning calorimetry, powder synchrotron X-ray diffraction, magnetic susceptibility measurements and 31P solid state NMR spectroscopy.

BackgroundIn vitro, animal model, and clinical evidence suggests that tuberculosis is not a monomorphic disease, and that host response to tuberculosis is protean with multiple distinct molecular pathways and pathologies (endotypes). We applied unbiased clustering to identify separate tuberculosis endotypes with classifiable gene expression patterns and clinical outcomes.MethodsA cohort comprised of microarray gene expression data from microbiologically confirmed tuberculosis patients were used to identify putative endotypes. One microarray cohort with longitudinal clinical outcomes was reserved for validation, as was one RNA-seq cohorts. Finally, a separate cohort of tuberculosis patients with functional immune results was evaluated to clarify stimulated from unstimulated immune responses.ResultsA discovery cohort, including 435 tuberculosis patients and 533 asymptomatic controls, identified two tuberculosis endotypes. Tuberculosis patient endotype A is characterized by increased expression of genes related to inflammation and immunity and decreased metabolism and proliferation; in contrast, endotype B increased activity of metabolism and proliferation pathways. An independent RNA-seq validation cohort, including 118 tuberculosis patients and 179 controls, validated the discovery results. Gene expression signatures for treatment failure were elevated in endotype A in the discovery cohort, and a separate validation cohort confirmed that endotype A patients had slower time to culture conversion, and a reduced incidence of cure. These observations suggest that endotypes reflect functional immunity, supported by the observation that tuberculosis patients with a hyperinflammatory endotype have less responsive cytokine production upon stimulation.ConclusionThese findings provide evidence that metabolic and immune profiling could inform optimization of endotype-specific host-directed therapies for tuberculosis.

Derailed cytokine and immune cell networks account for organ damage and clinical severity of COVID-19. Here we show that SARS-CoV-2, like other viruses, evokes cellular senescence as a primary stress response in infected cells. Virus-induced senescence (VIS) is indistinguishable from other forms of cellular senescence and accompanied by a senescence-associated secretory phenotype (SASP), composed of pro-inflammatory cytokines, extracellular matrix-active factors and pro-coagulatory mediators. COVID-19 patients displayed markers of senescence in their airway mucosa in situ and elevated serum levels of SASP factors. Mirroring COVID-19 hallmark features such as macrophage and neutrophil infiltration, endothelial damage and widespread thrombosis in affected lung tissue in vitro assays demonstrated macrophage activation with SASP-reminiscent secretion, complement lysis and SASP-amplifying secondary senescence of endothelial cells, neutrophil extracellular trap (NET) formation as well as activation of platelets and the clotting cascade in response to supernatant of VIS cells, including SARS-CoV-2-induced senescence. Senolytics such as Navitoclax and Dasatinib/Quercetin selectively eliminated VIS cells, mitigated COVID-19-reminiscent lung disease and reduced inflammation in SARS-CoV-2-driven hamster and mouse models. Our findings mark VIS as pathogenic trigger of COVID-19-related cytokine escalation and organ damage, and suggest senolytic targeting of virus-infected cells as a novel treatment option against SARS-CoV-2 and perhaps other viral infections.

Supplementary material for poster "Input representation and processing in a computational model of the rat primary somatosensory cortex" (P385.05) presented at SfN Global Connectome 2021. The files are organized per panel in the poster, with contents as follows: Panel C: three tables with connectivity statistics per pathway for each type of connectivity, and a Jupyter notebook to generate the figure Panel D: additional figure showing results of calibration of miniature PSCs for spontaneous synaptic release Panel E: full spike rasters and histograms per cell class for each parameter combination of the calcium-depolarization scan Panel F: spike rasters and histograms for increasing numbers of stimulated fibers with and without mid-range projections; for 24 stimulated fibers, full-scale spike raster and histogram for single column, spike rasters for all columns, movies of spiking activity as seen from above, movies of spiking activity as seen from above per layer, movies of spiking activity in a single column with audio (mapping cortical depth to frequency and number of spikes to amplitude) Panel G: full-scale versions of figures 2 and 3, plus additional spike rasters from in vivo and in silico data Panel H: full spike raster showing pattern presentations, This work was supported by funding to the Blue Brain Project, a research center of the École polytechnique fédérale de Lausanne (EPFL), from the Swiss government's ETH Board of the Swiss Federal Institutes of Technology.

Einleitung: Bedingt durch die Zulassung neuerer Substanzen wurde das Behandlungsspektrum der medikamentösen Therapie des Benignen Prostatasyndroms (BPS) in den letzten Jahren erweitert. Derzeit stehen fünf Substanzklassen zur Verfügung: Alphablocker, 5-Alpha-Reduktaseinhibitoren (5-ARI),[zum vollständigen Text gelangen Sie über die oben angegebene URL], 65. Kongress der Nordrhein-Westfälischen Gesellschaft für Urologie

Aluminum alloys are widely used in transportation industries because of the increasing need to reduce the environmental impact. With advances in technology, the demand for complex parts and components that must be produced using several processing methods has increased. During fabrication and service, a wide range of defects can appear in aluminum components and structures, which could be repaired using a suitable through hole closure method. The search for a friction-based solid-state keyhole repair technique that fulfills the requirements for high-quality repair welds has become an important research topic because conventional fusion welding is difficult to apply in many aluminum alloys. However, many commonly available friction-based welding methods are complex and multistage processes that require specially designed equipment and are not suitable for sealing through holes. The development of an adequate keyhole repair process is thus actual necessity. The present study addresses the development of a suitable keyhole repair procedure of structural aluminum parts using the refill friction stir spot welding process (RFSSW). For this newly developed repair method, a plug made of a similar material is applied as a filler element into the keyhole and RFSSW is used to weld the plug to the surrounding workpiece. To cover a wide range of alloys and potential applications, the repair method was investigated in different precipitation hardening aluminum alloys as well as different keyhole diameters and workpiece thicknesses. A fundamental analysis of the process and resulting material properties considering the alloy-dependent metallurgical transformations was conducted. Moreover, a knowledge-based process analysis approach was chosen to study the behavior of the base material during high-shear-rate plastic deformation and exposure to typical thermal cycles, which are both associated with the conditions found during friction welding. The influence of the base material composition and properties on the energy input during friction welding was investigated and a comprehensive analysis of the friction condition and flow stress development was conducted. The developed keyhole repair process using RFSSW is a universal through-hole closure method with advantages such as defect-free welds, high weld efficiencies and superior surface appearance on both sides of the weld. Within the scope of the present work, processing conditions were defined that lead to defect free repair welds for all investigated materials and workpiece dimensions. The area of lowest strength was in all cases found outside of the weld spot, mainly in the heat affected zone. For all welded precipitation hardening aluminum alloys, metallurgical analysis revealed that the evolution of the strengthening precipitates during and after the weld primarily determines the final mechanical properties. Significant differences observed in the response of the base materials to the process were found to be caused by the alloy composition, specifically by the characteristics of the present precipitates. The fundamental process analysis revealed that in precipitation hardening aluminum alloys, the mechanical properties obtained under quasi-static testing conditions are not adequate to describe or predict the base material properties at the high strain rates and thermal cycles associated with friction welding operations. The alloy composition, initial temper condition and general precipitation evolution during the specific thermal cycles resulting from the friction welding operations were found to determine the material properties at the tested rates of deformation. The knowledge gained by this fundamental process analysis is key to enabling rapid process optimization by guiding the appropriate choice of process parameters for a given alloy.