Influence of AFP Process Parameters on the Temperature Distribution Used for Thermal in-process Monitoring

Automated Fiber Placement is an important manufacturing process when it comes to aerospace part generation. To minimize the machine downtime, an online monitoring system is necessary to prevent time consuming visual inspection. Therefore, a new thermal in-process monitoring system is integrated. Herewith spotted temperature difference enable the localization of placed tows and detection of defects. The thermal contrast between subsurface and tows depends on different process parameters such as lay-up speed, tooling temperature and compaction pressure. This influence is analyzed and discussed within lay-up studies to gain further knowledge about the different effects to increase the reliability of in-process monitoring as well as AFP processes.Therm-O-PlanNiedersächsisches Vorab, Volkswagen Foundatio

Water vapor transport in the lower mesosphere of the subtropics: a trajectory analysis

The Institute of Applied Physics operates an airborne microwave radiometer AMSOS that measures the rotational transition line of water vapor at 183.3 GHz. Water vapor profiles are retrieved for the altitude range from 15 to 75 km along the flight track. We report on a water vapor enhancement in the lower mesosphere above India and the Arabian Sea. The measurements took place on our flight from Switzerland to Australia and back in November 2005 conducted during EC- project SCOUT-O3. We find an enhancement of up to 25% in the lower mesospheric H<sub>2</sub>O volume mixing ratio measured on the return flight one week after the outward flight. The origin of the air is traced back by means of a trajectory model in the lower mesosphere and wind fields from ECMWF. During the outward flight the air came from the Atlantic Ocean around 25 N and 40 W. On the return flight the air came from northern India and Nepal around 25 N and 90 E. Mesospheric H<sub>2</sub>O measurements from Aura/MLS confirm the transport processes of H<sub>2</sub>O derived by trajectory analysis of the AMSOS data. Thus the large variability of H<sub>2</sub>O VMR during our flight is explained by a change of the winds in the lower mesosphere. This study shows that trajectory analysis can be applied in the mesosphere and is a powerful tool to understand the large variability in mesospheric H<sub>2</sub>O

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part VI - Ultrasound-guided vascular interventions

The sixth part of the Guidelines on Interventional Ultrasound produced under the auspices of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) assesses the evidence for ultrasound guidance and assistance in vascular interventions. Based on convincing data, real-time sonographic guidance for central venous access is strongly recommended as a key safety measure. Systematic analysis of scientific literature shows that in difficult situations and special circumstances US guidance may also improve the efficacy and safety of peripheral venous and arterial access and endovascular interventions. Moreover, the recommendations of this guideline endorse the use of ultrasound to detect complications of vascular access and US-guided interventional treatment of arterial pseudoaneurysms.publishersversionPeer reviewe

Bioprinted Multi-Cell Type Lung Model for the Study of Viral Inhibitors

Influenza A virus (IAV) continuously causes epidemics and claims numerous lives every year. The available treatment options are insufficient and the limited pertinence of animal models for human IAV infections is hampering the development of new therapeutics. Bioprinted tissue models support studying pathogenic mechanisms and pathogen-host interactions in a human micro tissue environment. Here, we describe a human lung model, which consisted of a bioprinted base of primary human lung fibroblasts together with monocytic THP-1 cells, on top of which alveolar epithelial A549 cells were printed. Cells were embedded in a hydrogel consisting of alginate, gelatin and collagen. These constructs were kept in long-term culture for 35 days and their viability, expression of specific cell markers and general rheological parameters were analyzed. When the models were challenged with a combination of the bacterial toxins LPS and ATP, a release of the proinflammatory cytokines IL-1β and IL-8 was observed, confirming that the model can generate an immune response. In virus inhibition assays with the bioprinted lung model, the replication of a seasonal IAV strain was restricted by treatment with an antiviral agent in a dose-dependent manner. The printed lung construct provides an alveolar model to investigate pulmonary pathogenic biology and to support development of new therapeutics not only for IAV, but also for other viruses

A Critical Study on Acylating and Covalent Reversible Fragment Inhibitors of SARS-CoV-2 Main Protease Targeting the S1 Site with Pyridine

SARS coronavirus main proteases (3CL proteases) have been validated as pharmacological targets for the treatment of coronavirus infections. Current inhibitors of SARS main protease, including the clinically admitted drug nirmatrelvir are peptidomimetics with the downsides of this class of drugs including limited oral bioavailability, cellular permeability, and rapid metabolic degradation. Here, we investigate covalent fragment inhibitors of SARS Mpro as potential alternatives to peptidomimetic inhibitors in use today. Starting from inhibitors acylating the enzyme's active site, a set of reactive fragments was synthesized, and the inhibitory potency was correlated with the chemical stability of the inhibitors and the kinetic stability of the covalent enzyme-inhibitor complex. We found that all tested acylating carboxylates, several of them published prominently, were hydrolyzed in assay buffer and the inhibitory acyl-enzyme complexes were rapidly degraded leading to the irreversible inactivation of these drugs. Acylating carbonates were found to be more stable than acylating carboxylates, however, were inactive in infected cells. Finally, reversibly covalent fragments were investigated as chemically stable SARS CoV-2 inhibitors. Best was a pyridine-aldehyde fragment with an IC50 of 1.8 μM at a molecular weight of 211 g/mol, showing that pyridine fragments indeed are able to block the active site of SARS-CoV-2 main protease

Optimization of cell-laden bioinks for 3D bioprinting and efficient infection with influenza A virus

Bioprinting is a new technology, which arranges cells with high spatial resolution, but its potential to create models for viral infection studies has not yet been fully realized. The present study describes the optimization of a bioink composition for extrusion printing. The bioinks were biophysically characterized by rheological and electron micrographic measurements. Hydrogels consisting of alginate, gelatin and Matrigel were used to provide a scaffold for a 3D arrangement of human alveolar A549 cells. A blend containing 20% Matrigel provided the optimal conditions for spatial distribution and viability of the printed cells. Infection of the 3D model with a seasonal influenza A strain resulted in widespread distribution of the virus and a clustered infection pattern that is also observed in the natural lung but not in two-dimensional (2D) cell culture, which demonstrates the advantage of 3D printed constructs over conventional culture conditions. The bioink supported viral replication and proinflammatory interferon release of the infected cells. We consider our strategy to be paradigmatic for the generation of humanized 3D tissue models by bioprinting to study infections and develop new antiviral strategies.DFG, 325093850, Open Access Publizieren 2017 - 2018 / Technische Universität Berli

The Novel Human Influenza A(H7N9) Virus Is Naturally Adapted to Efficient Growth in Human Lung Tissue

A novel influenza A virus (IAV) of the H7N9 subtype has been isolated from severely diseased patients with pneumonia and acute respiratory distress syndrome and, apparently, from healthy poultry in March 2013 in Eastern China. We evaluated replication, tropism, and cytokine induction of the A/Anhui/1/2013 (H7N9) virus isolated from a fatal human infection and two low-pathogenic avian H7 subtype viruses in a human lung organ culture system mimicking infection of the lower respiratory tract. The A(H7N9) patient isolate replicated similarly well as a seasonal IAV in explanted human lung tissue, whereas avian H7 subtype viruses propagated poorly. Interestingly, the avian H7 strains provoked a strong antiviral type I interferon (IFN-I) response, whereas the A(H7N9) virus induced only low IFN levels. Nevertheless, all viruses analyzed were detected predominantly in type II pneumocytes, indicating that the A(H7N9) virus does not differ in its cellular tropism from other avian or human influenza viruses. Tissue culture-based studies suggested that the low induction of the IFN-β promoter correlated with an efficient suppression by the viral NS1 protein. These findings demonstrate that the zoonotic A(H7N9) virus is unusually well adapted to efficient propagation in human alveolar tissue, which most likely contributes to the severity of lower respiratory tract disease seen in many patients

Beyond the Jaynes-Cummings model: circuit QED in the ultrastrong coupling regime

In cavity quantum electrodynamics (QED), light-matter interaction is probed at its most fundamental level, where individual atoms are coupled to single photons stored in three-dimensional cavities. This unique possibility to experimentally explore the foundations of quantum physics has greatly evolved with the advent of circuit QED, where on-chip superconducting qubits and oscillators play the roles of two-level atoms and cavities, respectively. In the strong coupling limit, atom and cavity can exchange a photon frequently before coherence is lost. This important regime has been reached both in cavity and circuit QED, but the design flexibility and engineering potential of the latter allowed for increasing the ratio between the atom-cavity coupling rate and the cavity transition frequency above the percent level. While these experiments are well described by the renowned Jaynes-Cummings model, novel physics is expected in the ultrastrong coupling limit. Here, we report on the first experimental realization of a superconducting circuit QED system in the ultrastrong coupling limit and present direct evidence for the breakdown of the Jaynes-Cummings model.Comment: 5 pages, 3 figure