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A new concept for increasing process stability during milling processes is presented utilizing a parametric anti-resonance. The beneficial effect is examined by numerical calculations in the time domain for an example spindle which is supported conventionally by ball bearings and is equipped with an additional active magnetic bearing that enables the realization of a deliberate parametric excitation. In the present study the stiffness of this active support bearing is changed periodically with time. The parametric excitation is tuned to a parametric anti-resonance which triggers the transfer of vibration energy between the vibration modes of the underlying system without this additional time-periodicity. It is highlighted how vibration energy is transferred from the first bending mode of the rotor, which is the most critical one by means of regenerative chatter, to a mode with higher damping in order to increase the effective damping of the entire spindle drive unit.

Immune clearance of Hepatitis B virus (HBV) is characterized by broad and robust antiviral T cell responses, while virus-specific T cells in chronic hepatitis B (CHB) are rare and exhibit immune exhaustion that includes programmed-death-1 (PD-1) expression on virus-specific T cells. Thus, an immunotherapy able to expand and activate virus-specific T cells may have therapeutic benefit for CHB patients. Like HBV-infected patients, woodchucks infected with woodchuck hepatitis virus (WHV) can have increased hepatic expression of PD-1-ligand-1 (PD-L1), increased PD-1 on CD8+ T cells, and a limited number of virus-specific T cells with substantial individual variation in these parameters. We used woodchucks infected with WHV to assess the safety and efficacy of anti-PD-L1 monoclonal antibody therapy (αPD-L1) in a variety of WHV infection states. Experimentally-infected animals lacked PD-1 or PD-L1 upregulation compared to uninfected controls, and accordingly, αPD-L1 treatment in lab-infected animals had limited antiviral effects. In contrast, animals with naturally acquired WHV infections displayed elevated PD-1 and PD-L1. In these same animals, combination therapy with αPD-L1 and entecavir (ETV) improved control of viremia and antigenemia compared to ETV treatment alone, but with efficacy restricted to a minority of animals. Pre-treatment WHV surface antigen (sAg) level was identified as a statistically significant predictor of treatment response, while PD-1 expression on peripheral CD8+ T cells, T cell production of interferon gamma (IFN-γ) upon in vitro antigen stimulation (WHV ELISPOT), and circulating levels of liver enzymes were not. To further assess the safety of this strategy, αPD-L1 was tested in acute WHV infection to model the risk of liver damage when the extent of hepatic infection and antiviral immune responses were expected to be the greatest. No significant increase in serum markers of hepatic injury was observed over those in infected, untreated control animals. These data support a positive benefit/risk assessment for blockade of the PD-1:PD-L1 pathway in CHB patients and may help to identify patient groups most likely to benefit from treatment. Furthermore, the efficacy of αPD-L1 in only a minority of animals, as observed here, suggests that additional agents may be needed to achieve a more robust and consistent response leading to full sAg loss and durable responses through anti-sAg antibody seroconversion.

SHM is a growing field for new and ageing infrastructure around the globe. Not least, since revenues for industry, operators and insurances are becoming increasingly obvious. Offshore wind turbines (OWT) represent an ideal application case – Being expensive, critical infrastructure with a remote, sometimes inaccessible, location, SHM can help to increase availability and reduce costs for operation and maintenance. Furthermore, with a tall slender structure and a large head mass, WT have the tendency to an extensive dynamic behavior, facilitating vibration based SHM. In the field of SHM for OWT and WT, diverse research has been carried out and some industrial applications e.g. for ice detection on rotor blades exist. In the offshore wind industry, grouted connections between piles and support structure have been adapted from the oil and gas industry. Nevertheless, the dynamic loading differs significantly form the one at large offshore platforms in the oil and gas industry and a deep understanding for damage initiation, progress and consequences is not yet fully achieved and under investigation [1]. Nevertheless, most research deals with axial loading, typical for Jacket structures, and the favored solution for OTW being monopoles with a loading dominated by bending. The presented large scale tests in the test center for support structures in Hannover Germany focus on damage in such connections. After investigating the influence of scour, marine growth and loosened bolts in the preceding project UnderwaterINSPECT [2], the current project QS-M Grout focusses on damages at grouted connections. For this purpose, two grouted connections in transition pieces (TP) are tested and damaged in the current project. Both, in a sand pit with a pile as footing and in a span where damage relevant cyclic loads are applied to the TP. The paper focusses on two main points: One is the influence and decrease of the TP stiffness along with cyclic loading, the other is the damage detection through vibration based SHM procedures. In the second case different condition Parameters will be compared to each other to evaluate the SHM-performance. The two TP were initially placed into the sand pit, where a reference load was applied by an electrodynamic shaker, mounted on top of the structure.

Dengue virus (DENV) is a global disease threat for which there are no approved antivirals or vaccines. Establishing state-of-the-art screening systems that rely on fluorescent or luminescent reporters may accelerate the development of anti-DENV therapeutics. However, relatively few reporter DENV platforms exist. Here, we show that DENV can be genetically engineered to express a green fluorescent protein or firefly luciferase. Reporter viruses are infectious in vitro and in vivo and are sensitive to antiviral compounds, neutralizing antibodies, and interferons. Bioluminescence imaging was used to follow the dynamics of DENV infection in mice and revealed that the virus localized predominantly to lymphoid and gut-associated tissues. The high-throughput potential of reporter DENV was demonstrated by screening a library of more than 350 IFN-stimulated genes for antiviral activity. Several antiviral effectors were identified, and they targeted DENV at two distinct life cycle steps. These viruses provide a powerful platform for applications ranging from validation of vaccine candidates to antiviral discovery.

This paper reports on a radar-based structural health monitoring (SHM) system for wind turbine blades. Initial results are presented from a field installation at a 2 MW wind energy plant (WEP) where two FMCW radar systems with high output power are placed at the tower of the WEP. The frequency bands are 24.05-24.25GHz and 33.4-36.0GHz, respectively. The remote sensing inspection takes place when the blades pass the sensor system during normal WEP operation. Here, we present the concept and realization of this innovative SHM system, the synchronous data processing chain as well as experimental data from both radar sensors