The challenges of creating a universal influenza vaccine

The lack of population immunity to the periodically emerging pandemic influenza strains makes influenza infection especially dangerous. The fragmented nature of the influenza virus genome contributes to the formation of influenza virus reassortants containing genomic fragments from different strains. This mechanism is the main reason for the natural influenza virus antigenic diversity as well as for the occurrence of influenza pandemics. Vaccination is the best measure to prevent the spread of influenza infection, but the efficacy of existing vaccines is not sufficient, especially for the elderly and small children. Specific immunity, developed after disease or immunization, poorly protects against infection by influenza viruses of another subtype. In this regard, there is an urgent need for a more effective universal influenza vaccine that provides a long-lasting broad cross-protective immunity, and is able to protect against influenza A and B viruses of all known subtypes. The basic approaches to as well as challenges of creating such a vaccine are discussed in this review.The lack of population immunity to the periodically emerging pandemic influenza strains makes influenza infection especially dangerous. The fragmented nature of the influenza virus genome contributes to the formation of influenza virus reassortants containing genomic fragments from different strains. This mechanism is the main reason for the natural influenza virus antigenic diversity as well as for the occurrence of influenza pandemics. Vaccination is the best measure to prevent the spread of influenza infection, but the efficacy of existing vaccines is not sufficient, especially for the elderly and small children. Specific immunity, developed after disease or immunization, poorly protects against infection by influenza viruses of another subtype. In this regard, there is an urgent need for a more effective universal influenza vaccine that provides a long-lasting broad cross-protective immunity, and is able to protect against influenza A and B viruses of all known subtypes. The basic approaches to as well as challenges of creating such a vaccine are discussed in this review

Tsunami wave generation by the eruption of underwater volcano

International audienceEruption of volcanoes represents one of important origins of tsunami waves and is responsible for most catastrophic tsunami (Krakatau, 1883; Thira, BC). The products of volcano eruption include solids, liquids (lava) and gases. The present article presents hydrodynamic model of relatively slow process of eruption, with domination of liquids. The process of underwater eruption of lava causes the disturbance of ocean free surface. The standard formulation of hydrodynamic problem for incompressible fluid in cylindrically symmetric layer of with rigid bottom and free surface with local hydrodynamic source (volcano) is used. This problem is solved by constructing Green function using methodology of Sretenskij. The solution is obtained in the form of an integral and depends on the dynamics of eruption. Real data show that some volcanoes can erupt several millions of tons of lava during several dozens of seconds (Bezimjannij, Kamchatka). The long waves are more efficiently generated by larger T: these tsunamis can have smaller initial perturbations of free surface, but the waves are long and can transmit their energy over longer distances

The exercise paradox: An interactional model for a clearer conceptualization of exercise addiction

Background and aims: Exercise addiction receives substantial attention in the field of behavioral addictions. It is a unique form of addiction because in contrast to other addictive disorders it is carried out with major physical-effort and high energy expenditure. Methods: A critical literature review was performed. Results: The literature evaluation shows that most published accounts report the levels of risk for exercise addiction rather than actual cases or morbidities. The inconsistent prevalence of exercise addiction, ranging from 0.3% to 77.0%, reported in the literature may be ascribed to incomplete conceptual models for the morbidity. Current explanations of exercise addiction may suggest that the disorder is progressive from healthy to unhealthy exercise pattern. This approach drives research into the wrong direction. Discussion: An interactional model is offered accounting for the adoption, maintenance, and transformation of exercise behavior. The here proposed model has an idiosyncratic black-box containing the antecedents and characteristics that are unique to the individual, which cannot be researched via the nomothetic approach. Subjective aspects in the black-box interact with stressful life events that force the person to cope. The range of coping may be wide. Escape into exercise depends on personal (subjective) and situational (objective) factors, but the subjective components are inaccessible for a priori scholastic scrutiny. It is our view that currently only this dual interactional model may account for the fact that exercise addiction emerges suddenly and only in a few individuals from among those at high risk, estimated to be around 3.0% of the exercising population

Enhanced CD8+ T-cell response in mice immunized with NS1-truncated influenza virus

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.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

Multi-domain active sound control and noise shielding

This paper describes an active sound control methodology based on difference potentials. The main feature of this methodology is its ability to automatically preserve “wanted” sound within a domain while canceling “unwanted” noise from outside the domain. This method of preservation of the wanted sounds by active shielding control is demonstrated with various broadband and realistic sound sources such as human voice and music in multiple domains in a one-dimensional enclosure. Unlike many other conventional active control methods, the proposed approach does not require the explicit characterization of the wanted sound to be preserved. The controls are designed based on the measurements of the total field on the boundaries of the shielded domain only, which is allowed to be multiply connected. The method is tested in a variety of experimental cases. The typical attenuation of the unwanted noise is found to be about 20 dB over a large area of the shielded domain and the original wanted sound field is preserved with errors of around 1 dB and below through a broad frequency range up to 1 kHz. © 2011 Acoustical Society of Americ

Search for Sterile Neutrinos with a Radioactive Source at Daya Bay

The far site detector complex of the Daya Bay reactor experiment is proposed as a location to search for sterile neutrinos with > eV mass. Antineutrinos from a 500 kCi 144Ce-144Pr beta-decay source (DeltaQ=2.996 MeV) would be detected by four identical 20-ton antineutrino targets. The site layout allows flexible source placement; several specific source locations are discussed. In one year, the 3+1 sterile neutrino hypothesis can be tested at essentially the full suggested range of the parameters Delta m^2_{new} and sin^22theta_{new} (90% C.L.). The backgrounds from six nuclear reactors at >1.6 km distance are shown to be manageable. Advantages of performing the experiment at the Daya Bay far site are described

Observation of microbial carbonate build-ups growing at methane seeps near the upper boundary of the gas-hydrate stability zone in the Black Sea

Extensive dredge sampling carried out in May-June 2004 in the deeper part of the Dnepr paleo-delta area (NW Black Sea) yielded for the first time chimney-shaped carbonate microbial build-ups, which occur at methane seeps close to upper boundary of the gas-hydrate stability zone (~ 700 m). Carbonate samples taken with a benthic trawl represent fragments of the uppermost, middle and lowest parts of the build-up; they are similar morphologically to those found previously at the shallower and deeper methane seeps in the Black Sea. At the same time, the perforated, plate-like carbonates in the lowest parts of the build-up provide first indications that gas channels are formed during the earliest growth phase of these microbial structures. Stable carbon isotope analyses of the carbonates from the uppermost fragments gave the 5I3C values ranging from -33.7 to -36.6 %o, while the 813C values of the lowest fragments are significantly lighter, varying between -42.0 and -44.6 %o. Oxygen isotopic values also show differences between the samples from the uppermost part of the build-ups, which are composed of a mixture of aragonite and Mg-calcite (5180 = 0.7 to 0.94 %o), and the only Mg-calcite cemented thin slabs of lowest carbonates (5180 = 1.35 to 1.57 96o). The isotope data for carbon and oxygen suggests that carbonates formed as a result of anaerobic microbiological oxi­dation of methane supplied as a shallower-sourced fluid component from below. The difference in 513C and 5I80 values found in the upper and lowest parts of the build-ups may indicate that more carbon derived from seawater and less hydrate water are involved to the chimney formation during its growth, but this may be also a record of the long-term changes in the near-bottom environments related to evolution of salinity, temperature and anoxic conditions in the Black Sea

Effect of Copper Doping on Charge Ordering in La 1/3 Ca 2/3 Mn 1 - y Cu y O 3 (0 ≤ y ≤ 0.07)

Electron microscope studies have shown that the presence of copper suppresses the formation of a regular superstructure, which is characteristic of the undoped starting compound, beginning already from low concentrations (y=0.01). Differential scanning calorimetry revealed a substantial decrease in the transition entropy at the onset of charge ordering in copper-doped samples as compared to the starting compound. Doping with copper destroys long-range charge-orbital ordering and retains apparently only short-range orderyesBelgorod State Universit