Antigenic evolution of human influenza H3N2 neuraminidase is constrained by charge balancing

As one of the main influenza antigens, neuraminidase (NA) in H3N2 virus has evolved extensively for more than 50 years due to continuous immune pressure. While NA has recently emerged as an effective vaccine target, biophysical constraints on the antigenic evolution of NA remain largely elusive. Here, we apply combinatorial mutagenesis and next-generation sequencing to characterize the local fitness landscape in an antigenic region of NA in six different human H3N2 strains that were isolated around 10 years apart. The local fitness landscape correlates well among strains and the pairwise epistasis is highly conserved. Our analysis further demonstrates that local net charge governs the pairwise epistasis in this antigenic region. In addition, we show that residue coevolution in this antigenic region is correlated with the pairwise epistasis between charge states. Overall, this study demonstrates the importance of quantifying epistasis and the underlying biophysical constraint for building a model of influenza evolution.

Switched capacitor based multi-level boost inverter for smart grid applications

To link DC power sources to an AC grid, converters are needed. Inverters are the power electronic devices, which are used for this purpose. Conventional inverters employ harmonic filters and transformers that are lossy and expensive. Multilevel inverters (MLIs) are an alternative to conventional ones, proposing reduced total harmonic distortion (THD), increased range of control, and inductor-less design. They generate a stepped waveform, with close similarity to a sine wave. Many distributed sources may be employed in a smart grid. If those sources have minimal THD, the filtering process could be reduced at the point of common coupling. This paper presents two switched capacitor based MLIs, proposing boost capability and low THD. Inverters have inherent charge balancing capability, which eliminates the need for auxiliary circuits and voltage sensors. Inverters switches are modulated using phase opposition disposition pulse-width modulation (PODPWM) method that ease the balancing of the voltage and decrease the losses of switching. Designs were verified by simulation and the output waveforms were introduced.