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Influenza viruses with truncated NS1 protein stimulate a more intensive innate immune response compared to their wild type counterparts. Here, we investigate how the shortening of the NS1 protein influence the immunogenicity of the conserved T-cellular epitopes of influenza virus. Using flow cytometry, we showed that the intraperitoneal immunization of mice with influenza virus encoding 124 N-terminal amino acid residues of the NS1 protein (A/PR8/NS124) induced higher levels of CD8+ T-cells recognizing immunodominant (NP366-374) and sub-immunodominant (NP161-175, NP196-210, HA323-337, HA474-483, NA427-433) epitopes compared to immunization with the virus expressing full-length NS1 (A/PR8/full NS). It is noteworthy that the response to the immunodominant influenza epitope NP366-374 was achieved with the lower immunization dose of A/PR8/NS124 virus compared to the reference wild type strain. Despite the fact that polyfunctional CD8+ effector memory T-lymphocytes simultaneously producing two (IFNγ and TNFα) or three (IFNγ, IL2 and TNFα) cytokines prevailed in the immune response to both viruses, the relative number of such T-cells was higher in A/PR8/NS124-immunized mice. Furthermore, we have found that polyfunctional populations of lymphocytes generated upon the immunization of mice with the mutant virus demonstrated an increased capacity to produce IFNγ compared to the corresponding populations derived from the A/PR8/full NS-immunized mice. Therefore, immunization with the attenuated influenza virus encoding truncated NS1 protein ensures a more potent CD8+ T-cell immune response.

A simple miniature source generating pulse trains with a central frequency of ∼100 GHz and a duration of 50–100 ps has been demonstrated recently. The source is based on nanometer-scale collapsing field domains (CFDs) generated in the collector of an avalanching bipolar GaAs transistor. The central frequency is determined by the domain transient time across the collector, and thus, a routine increase in the oscillation frequency from 0.1 to 0.3–0.5 THz would require a reduction in the collector thickness by a factor of 3–5. This is not acceptable, however, since it would reduce the maximum blocking voltage affecting the achievable peak current across the avalanche switch. We suggest here a solution to this challenging problem by reducing the CFD travel distance while keeping the collector thickness unchanged. Here, the discovered and interpreted phenomenon of CFD collapse when entering a dense carrier plasma zone made it possible by means of bandgap engineering. A CFD emitter generating ∼200 GHz wavetrains of ∼100 ps in duration is demonstrated. This finding opens an avenue for the increase in the oscillation frequency without any reduction in the emitted power, by using a smart structure design.

The truncation of the nonstructural NS1 protein is a novel approach for the generation of immunogenic attenuated influenza viruses. However, the innate immune mechanisms that cause the increased immunogenicity of influenza viruses with altered NS1 proteins are poorly understood. The goal of this study was to compare the immune responses in mice immunized with two variants of the influenza A/Puerto Rico/8/1934 (A/PR8) virus: the wild type virus (А/PR8/full NS) and the variant with the NS1 protein shortened to 124 amino acid residues (А/PR8/NS124). The investigated parameters of immunity included cytokine production, the dynamic variation of the innate immune cell populations, and the rate of the influenza-specific T-cell responses. An intraperitoneal route of immunization was chosen due to the variability in the replication capacity of the investigated viruses in the respiratory tract. The levels of interferon β (IFNβ), tumor necrosis factor α (TNFα), monocyte chemo-attractant protein 1 (MCP1), interleukin 6 (IL6), and IL27 in peritoneal washings of mice immunized with А/PR8/NS124 were significantly higher compared to the mice immunized with the wild-type virus. The А/PR8/NS124 treated group showed a delayed attraction of monocytes and neutrophils as well as a more pronounced reduction in the percentage of dendritic cells in the peritoneal cavity. The expression level of the CD86 activation marker on the cells expressing the molecules of the major histocompatibility complex II (MHCII+) was significantly higher in mice immunized with А/PR8/NS124 than in the group immunized with А/PR8/full NS. Finally, immunization with А/PR8/NS124 led to an increased formation of influenza-specific CD8+ effector T-cells characterized by the simultaneous production of IFNγ, IL2, and TNFα. We hypothesize that elevated cytokine production, enhanced dendritic cell migration, and increased CD86 expression on antigen-presenting cells upon immunization with А/PR8/NS124 lead to a more effective presentation of viral antigens and, therefore, promote an increased antigen-specific CD8+ immune response.

Modern medical science considers cervical dystonia as a single nosological form. However, half of the patients have a right-handed form. The second half has a left-handed form. Clinical and neurophysiological differences between these forms are discussed in the article. 15.1% had additional others hyperkinetic manifestations. Left-handed forms had head tremor. Right-handed forms have аthetoid hyperkines on the side of head rotation and oromandibular dystonia. Significant differences between the two forms are identified on the EEG. Differences were found in the results of treatment. Transtimpanal chemical vestibular dereception was the method of treatment of these patients.