Recognition of homo- and heterosubtypic variants of influenza A viruses by human CD8+ T lymphocytes

In the present study, the recognition of epitope variants of influenza A viruses by human CTL was investigated. To this end, human CD8(+) CTL clones, specific for natural variants of the HLA-B*3501-restricted epitope in the nucleoprotein (NP(418-426)), were generated. As determined in (51)Cr release assays and by flow cytometry with HLA-B*3501-peptide tetrameric complexes, CTL clones were found to be specific for epitopes within one subtype or cross-reactive with heterosubtypic variants of the epitope. Using eight natural variants of the epitope, positions in the 9-mer important for T cell recognition and involved in escape from CTL immunity were identified and visualized using multidimensional scaling. It was shown that positions 4 and 5 in the 9-mer epitope were important determinants of T cell specificity. The in vivo existence of CD8(+) cells cross-reactive with homo- and heterosubtypic variants of the epitope was further confirmed using polyclonal T cell populations obtained after stimulation of PBMC with different influenza A viruses. Based on the observed recognition patterns of the clonal and polyclonal T cell populations and serology, it is hypothesized that consecutive infections with influenza viruses containing different variants of the epitope select for cross-reactive T cells in vivo

Particle production and classical condensates in de Sitter space

The cosmological particle production in a $k=0$ expanding de Sitter universe with a Hubble parameter $H_0$ is considered for various values of mass or conformal coupling of a free, scalar field. One finds that, for a minimally coupled field with mass $0 \leq m^2 < 9 H_0^2/4$ (except for $m^2= 2H_0^2$), the one-mode occupation number grows to unity soon after the physical wavelength of the mode becomes larger than the Hubble radius, and afterwards diverges as $n(t) \sim O(1)(\lambda_{phys}(t)/H_0^{-1})^{2\nu}$, where $\nu \equiv [9/4 - m^2/H_0^2]^{1/2}$. However, for a field with $m^2 > 9H_0^2/4$, the occupation number of a mode outside the Hubble radius is rapidly oscillating and bounded and does not exceed unity. These results, readily generalized for cases of a nonminimal coupling, provide a clear argument that the long-wavelength vacuum fluctuations of low-mass fields in an inflationary universe do show classical behavior, while those of heavy fields do not. The interaction or self-interaction does not appear necessary for the emergence of classical features, which are entirely due to the rapid expansion of the de Sitter background and the upside-down nature of quantum oscillators for modes outside the Hubble radius.Comment: Revtex + 5 postscript figures. Accepted for Phys Rev D15. Revision of Aug 1996 preprint limited to the inclusion and discussion of references suggested by the referee

Interaction of Hawking radiation with static sources in deSitter and Schwarzschild-deSitter spacetimes

We study and look for similarities between the response rates $R^{\rm dS}(a_0, \Lambda)$ and $R^{\rm SdS}(a_0, \Lambda, M)$ of a static scalar source with constant proper acceleration $a_0$ interacting with a massless, conformally coupled Klein-Gordon field in (i) deSitter spacetime, in the Euclidean vacuum, which describes a thermal flux of radiation emanating from the deSitter cosmological horizon, and in (ii) Schwarzschild-deSitter spacetime, in the Gibbons-Hawking vacuum, which describes thermal fluxes of radiation emanating from both the hole and the cosmological horizons, respectively, where $\Lambda$ is the cosmological constant and $M$ is the black hole mass. After performing the field quantization in each of the above spacetimes, we obtain the response rates at the tree level in terms of an infinite sum of zero-energy field modes possessing all possible angular momentum quantum numbers. In the case of deSitter spacetime, this formula is worked out and a closed, analytical form is obtained. In the case of Schwarzschild-deSitter spacetime such a closed formula could not be obtained, and a numerical analysis is performed. We conclude, in particular, that $R^{\rm dS}(a_0, \Lambda)$ and $R^{\rm SdS}(a_0, \Lambda, M)$ do not coincide in general, but tend to each other when $\Lambda \to 0$ or $a_0 \to \infty$. Our results are also contrasted and shown to agree (in the proper limits) with related ones in the literature.Comment: ReVTeX4 file, 9 pages, 5 figure

The extremal limits of the C-metric: Nariai, Bertotti-Robinson and anti-Nariai C-metrics

In two previous papers we have analyzed the C-metric in a background with a cosmological constant, namely the de Sitter (dS) C-metric, and the anti-de Sitter (AdS) C-metric, following the work of Kinnersley and Walker for the flat C-metric. These exact solutions describe a pair of accelerated black holes in the flat or cosmological constant background, with the acceleration A being provided by a strut in-between that pushes away the two black holes. In this paper we analyze the extremal limits of the C-metric in a background with generic cosmological constant. We follow a procedure first introduced by Ginsparg and Perry in which the Nariai solution, a spacetime which is the direct topological product of the 2-dimensional dS and a 2-sphere, is generated from the four-dimensional dS-Schwarzschild solution by taking an appropriate limit, where the black hole event horizon approaches the cosmological horizon. Similarly, one can generate the Bertotti-Robinson metric from the Reissner-Nordstrom metric by taking the limit of the Cauchy horizon going into the event horizon of the black hole, as well as the anti-Nariai by taking an appropriate solution and limit. Using these methods we generate the C-metric counterparts of the Nariai, Bertotti-Robinson and anti-Nariai solutions, among others. One expects that the solutions found in this paper are unstable and decay into a slightly non-extreme black hole pair accelerated by a strut or by strings. Moreover, the Euclidean version of these solutions mediate the quantum process of black hole pair creation, that accompanies the decay of the dS and AdS spaces

A parallel non-neural trigger tracker for the SSC

The Superconducting Super Collider (SSC) is a major project promising to open the vistas of very high particle physics. When the SSC is in operation, data will be produced at a staggering rate. Current estimates place the raw data coming our of the proposed silicon detector system at 2.5 {times} 10{sup 16} bits/second. Clearly, storing all events for later off-line processing is totally impracticable. A hierarchy of triggers, firing only on events meeting increasingly specific criteria, are planned to cull interesting events from the flood of information. Each event consists of a sequence of isolated hits'', caused by particles hitting various parts of the detector. Collating these hits into the tracks of the approximately 500 particles/event, and then quickly deciding which events meet the criteria for later processing, is essential if the SSC is to produce usable information. This paper addresses the need for real-time triggering and track reconstruction. A benchmarked and buildable algorithm, operable at the required data rates, is described. The use of neural nets, suggested by other researchers, is specifically avoided as unnecessary and impractical. Instead, a parallel algorithm, and associated hardware architecture using only conventional technology, is presented. The algorithm has been tested on fully scaled up, extensively detailed, simulated SSC events, with extremely encouraging results. Preliminary hardware analysis indicate that the trigger/tracker may be built within proposed SSC budget guidelines. 7 refs., 4 figs

A Maximum Entropy Formalism for Disentangling Chains of Correlated Sequence Positions

Covariation analysis of sets of aligned sequences of protein molecules is successful in certain instances in elucidating certain structural and functional links, but in general, pairs of sites displaying highly covarying mutations in protein sequences do not necessarily correspond to sites that are spatially close in the protein structure. In contrast, covariation analysis of sets of aligned sequences for RNA molecules is relatively successful in elucidating RNA secondary structure, as well as some aspects of tertiary structure. The goals of this paper are to (1) present the problem, (2) develop the mathematical formalism for solving the problem, and (3) validate the resulting algorithms on simulated data. Extensive application to biological sequences will be presented elsewhere

Covariation of mutations: A computational approach for determination of function and structure from sequence

The authors have developed and enhanced a set of tools for fold recognition with hidden Markov models (HMMs), and used these tools effectively in the CASP2 protein structure prediction contest [KKB+97]. HMMs have limitations, and one limitation is that they do not model the long-range pairwise interactions that define the shape of a protein. As such, the authors are working on modeling pairwise interactions to incorporate them into the HMM-based framework. Classical fold recognition methods are based on the premise of distinct pairwise preferences between two given amino acids. The authors have studied these preferences extensively and found that in the general case, this information is limited. Yet by modeling pairwise interactions in context of phylogenetic relationships and by modeling one specific type of contact, the contact between interacting beta strand residues, they have recovered significant information for prediction and analysis of protein structure

Identification of continuous-time dynamical systems: Neural network based algorithms and parallel implementation

Time-delay mappings constructed using neural networks have proven successful performing nonlinear system identification; however, because of their discrete nature, their use in bifurcation analysis of continuous-tune systems is limited. This shortcoming can be avoided by embedding the neural networks in a training algorithm that mimics a numerical integrator. Both explicit and implicit integrators can be used. The former case is based on repeated evaluations of the network in a feedforward implementation; the latter relies on a recurrent network implementation. Here the algorithms and their implementation on parallel machines (SIMD and MIMD architectures) are discussed

Antigenic and genetic evolution of swine influenza A (H3N2) viruses in Europe

In the early 1970s, a human influenza A/Port Chalmers/1/73 (H3N2)-like virus colonized the European swine population. Analyses of swine influenza A (H3N2) viruses isolated in The Netherlands and Belgium revealed that in the earl