Viral proteins often display several functions which require multiple assays to dissect their genetic basis. Here, we describe a systematic approach to screen for loss-of-function mutations that confer a fitness disadvantage under a specified growth condition. Our methodology was achieved by genetically monitoring a mutant library under two growth conditions, with and without interferon, by deep sequencing. We employed a molecular tagging technique to distinguish true mutations from sequencing error. This approach enabled us to identify mutations that were negatively selected against, in addition to those that were positively selected for. Using this technique, we identified loss-of-function mutations in the influenza A virus NS segment that were sensitive to type I interferon in a high-throughput fashion. Mechanistic characterization further showed that a single substitution, D92Y, resulted in the inability of NS to inhibit RIG-I ubiquitination. The approach described in this study can be applied under any specified condition for any virus that can be genetically manipulated. IMPORTANCETraditional genetics focuses on a single genotype-phenotype relationship, whereas high-throughput genetics permits phenotypic characterization of numerous mutants in parallel. High-throughput genetics often involves monitoring of a mutant library with deep sequencing. However, deep sequencing suffers from a high error rate (ϳ0.1 to 1%), which is usually higher than the occurrence frequency for individual point mutations within a mutant library. Therefore, only mutations that confer a fitness advantage can be identified with confidence due to an enrichment in the occurrence frequency. In contrast, it is impossible to identify deleterious mutations using most next-generation sequencing techniques. In this study, we have applied a molecular tagging technique to distinguish true mutations from sequencing errors. It enabled us to identify mutations that underwent negative selection, in addition to mutations that experienced positive selection. This study provides a proof of concept by screening for loss-of-function mutations on the influenza A virus NS segment that are involved in its anti-interferon activity.

We demonstrate a compact, robust, and stable terahertz source based on a novel two section digital distributed feedback laser diode and plasmonic photomixer. Terahertz wave generation is achieved through difference frequency generation by pumping the plasmonic photomixer with two output optical beams of the two section digital distributed feedback laser diode. The laser is designed to offer an adjustable terahertz frequency difference between the emitted wavelengths by varying the applied currents to the laser sections. The plasmonic photomixer is comprised of an ultrafast photoconductor with plasmonic contact electrodes integrated with a logarithmic spiral antenna. We demonstrate terahertz wave generation with 0.15-3 THz frequency tunability, 2 MHz linewidth, and less than 5 MHz frequency stability over 1 minute, at useful power levels for practical imaging and sensing applications.

We present a study on perpendicular magnetic tunnel junctions with W as buffer and capping layers. A tunneling magnetoresistance of 138% and an interfacial magnetic anisotropy of 1.67 erg/cm 2 were obtained in optimally annealed samples. However, after extended annealing at 420 C, junctions with W layers showed extremely small resistance due to interdiffusion of W into the MgO barrier. In contrast, in Ta-based junctions, the MgO barrier remained structurally stable despite disappearance of magnetoresistance after extended annealing due to loss of perpendicular magnetic anisotropy. Compared with conventional tunnel junctions with in-plane magnetic anisotropy, the evolution of tunneling conductance suggests that the relatively low magnetoresistance in perpendicular tunnel junctions is related to the lack of highly polarized D 1 conducting channel developed in the initial stage of annealing.

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The magnetoelectric properties of exchangecoupled Ni/ CoFeB-based composite multiferroic microstructures are investigated. The strength and sign of the magnetoelastic effect are found to be strongly correlated with the ratio between the thicknesses of two magnetostrictive materials. In cases where the thickness ratio deviates significantly from one, the magnetoelastic behavior of the multiferroic microstructures is dominated by the thicker layer, which contributes more strongly to the observed magnetoelastic effect. More symmetric structures with a thickness ratio equal to one show an emergent interfacial behavior which cannot be accounted for simply by summing up the magnetoelastic effects occurring in the two constituent layers. This aspect is clearly visible in the case of ultrathin bilayers, where the exchange coupling drastically affects the magnetic behavior of the Ni layer, making the Ni/CoFeB bilayer a promising nextgeneration synthetic magnetic system entirely. This study demonstrates the richness and high tunability of composite multiferroic systems based on coupled magnetic bilayers compared to their single magnetic layer counterparts. Furthermore, because of the compatibility of CoFeB with present magnetic tunnel junction-based spintronic technologies, the reported findings are expected to be of great interest for the development of ultralow-power magnetoelectric memory devices.