119 research outputs found

    Transformation-based spherical cloaks designed by an implicit transformation-independent method: theory and optimization

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    Based on the concept of the cloak generating function, we propose an implicit transformation-independent method for the required parameters of spherical cloaks without knowing the needed coordinate transformation beforehand. A non-ideal discrete model is used to calculate and optimize the total scattering cross-sections of different profiles of the generating function. A bell-shaped quadratic spherical cloak is found to be the best candidate, which is further optimized by controlling the design parameters involved. Such improved invisibility is steady even when the model is highly discretized.European Commission (European Network of Excellence 'METAMORPHOSE')Foundation for Fundamental Research (Belarus) (F08MS-06

    Protection against Divergent Influenza H1N1 Virus by a Centralized Influenza Hemagglutinin

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    Influenza poses a persistent worldwide threat to the human population. As evidenced by the 2009 H1N1 pandemic, current vaccine technologies are unable to respond rapidly to this constantly diverging pathogen. We tested the utility of adenovirus (Ad) vaccines expressing centralized consensus influenza antigens. Ad vaccines were produced within 2 months and protected against influenza in mice within 3 days of vaccination. Ad vaccines were able to protect at doses as low as 107 virus particles/kg indicating that approximately 1,000 human doses could be rapidly generated from standard Ad preparations. To generate broadly cross-reactive immune responses, centralized consensus antigens were constructed against H1 influenza and against H1 through H5 influenza. Twenty full-length H1 HA sequences representing the main branches of the H1 HA phylogenetic tree were used to create a synthetic centralized gene, HA1-con. HA1-con minimizes the degree of sequence dissimilarity between the vaccine and existing circulating viruses. The centralized H1 gene, HA1-con, induced stronger immune responses and better protection against mismatched virus challenges as compared to two wildtype H1 genes. HA1-con protected against three genetically diverse lethal influenza challenges. When mice were challenged with 1934 influenza A/PR/8/34, HA1-con protected 100% of mice while vaccine generated from 2009 A/TX/05/09 only protected 40%. Vaccination with 1934 A/PR/8/34 and 2009 A/TX/05/09 protected 60% and 20% against 1947 influenza A/FM/1/47, respectively, whereas 80% of mice vaccinated with HA1-con were protected. Notably, 80% of mice challenged with 2009 swine flu isolate A/California/4/09 were protected by HA1-con vaccination. These data show that HA1-con in Ad has potential as a rapid and universal vaccine for H1N1 influenza viruses

    Internal flows and energy circulation in light beams

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    We review optical phenomena associated with the internal energy redistribution which accompany propagation and transformations of monochromatic light fields in homogeneous media. The total energy flow (linear-momentum density, Poynting vector) can be divided into spin part associated with the polarization and orbital part associated with the spatial inhomogeneity. We give general description of the internal flows in the coordinate and momentum (angular spectrum) representations for both nonparaxial and paraxial fields. This enables one to determine local densities and integral values of the spin and orbital angular momenta of the field. We analyse patterns of the internal flows in standard beam models (Gaussian, Laguerre-Gaussian, flat-top beam, etc.), which provide an insightful picture of the energy transport. The emphasize is made to the singular points of the flow fields. We describe the spin-orbit and orbit-orbit interactions in the processes of beam focusing and symmetry breakdown. Finally, we consider how the energy flows manifest themselves in the mechanical action on probing particles and in the transformations of a propagating beam subjected to a transverse perturbation.Comment: 50 pages, 21 figures, 173 references. This is the final version of the manuscript (v1) modified in accord to the referee's remarks and with allowance for the recent development. The main changes are: additional discussion of the energy flows in Bessel beams (section 4.1), a lot of new references are added and the Conclusion is shortened and made more accurat

    Evolutionary Modeling of Rate Shifts Reveals Specificity Determinants in HIV-1 Subtypes

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    A hallmark of the human immunodeficiency virus 1 (HIV-1) is its rapid rate of evolution within and among its various subtypes. Two complementary hypotheses are suggested to explain the sequence variability among HIV-1 subtypes. The first suggests that the functional constraints at each site remain the same across all subtypes, and the differences among subtypes are a direct reflection of random substitutions, which have occurred during the time elapsed since their divergence. The alternative hypothesis suggests that the functional constraints themselves have evolved, and thus sequence differences among subtypes in some sites reflect shifts in function. To determine the contribution of each of these two alternatives to HIV-1 subtype evolution, we have developed a novel Bayesian method for testing and detecting site-specific rate shifts. The RAte Shift EstimatoR (RASER) method determines whether or not site-specific functional shifts characterize the evolution of a protein and, if so, points to the specific sites and lineages in which these shifts have most likely occurred. Applying RASER to a dataset composed of large samples of HIV-1 sequences from different group M subtypes, we reveal rampant evolutionary shifts throughout the HIV-1 proteome. Most of these rate shifts have occurred during the divergence of the major subtypes, establishing that subtype divergence occurred together with functional diversification. We report further evidence for the emergence of a new sub-subtype, characterized by abundant rate-shifting sites. When focusing on the rate-shifting sites detected, we find that many are associated with known function relating to viral life cycle and drug resistance. Finally, we discuss mechanisms of covariation of rate-shifting sites

    Biology of moderately halophilic aerobic bacteria

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    The moderately halophilic heterotrophic aerobic bacteria form a diverse group of microorganisms. The property of halophilism is widespread within the bacterial domain. Bacterial halophiles are abundant in environments such as salt lakes, saline soils, and salted food products. Most species keep their intracellular ionic concentrations at low levels while synthesizing or accumulating organic solutes to provide osmotic equilibrium of the cytoplasm with the surrounding medium. Complex mechanisms of adjustment of the intracellular environments and the properties of the cytoplasmic membrane enable rapid adaptation to changes in the salt concentration of the environment. Approaches to the study of genetic processes have recently been developed for several moderate halophiles, opening the way toward an understanding of haloadaptation at the molecular level. The new information obtained is also expected to contribute to the development of novel biotechnological uses for these organisms

    MHC-I peptides get out of the groove and enable a novel mechanism of HIV-1 escape

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    Major histocompatibility complex class I (MHC-I) molecules play a crucial role in immunity by capturing peptides for presentation to T cells and natural killer (NK) cells. The peptide termini are tethered within the MHC-I antigen-binding groove, but it is unknown whether other presentation modes occur. Here we show that 20% of the HLA-B*57:01 peptide repertoire comprises N-terminally extended sets characterized by a common motif at position 1 (P1) to P2. Structures of HLA-B*57:01 presenting N-terminally extended peptides, including the immunodominant HIV-1 Gag epitope TW10 (TSTLQEQIGW), showed that the N terminus protrudes from the peptide-binding groove. The common escape mutant TSNLQEQIGW bound HLA-B*57:01 canonically, adopting a dramatically different conformation than the TW10 peptide. This affected recognition by killer cell immunoglobulin-like receptor (KIR) 3DL1 expressed on NK cells. We thus define a previously uncharacterized feature of the human leukocyte antigen class I (HLA-I) immunopeptidome that has implications for viral immune escape. We further suggest that recognition of the HLA-B*57:01-TW10 epitope is governed by a 'molecular tension' between the adaptive and innate immune systems
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