Two major antigenic subgroups (designated A and B) have been described for human respiratory syncytial virus (RSV). Previously, on the basis of reactivity patterns with monoclonal antibodies, the greatest intersubgroup variation was shown to occur in the G protein, the putative attachment glycoprotein. To delineate the molecular basis for this variation, we have determined the nucleotide and deduced amino acid sequences of the G mRNAs and proteins representing a subgroup A (Long strain) and a subgroup B (18537 strain) virus. These sequences were compared to the available G mRNA sequence for another subgroup A (A2 strain) virus. The Long G protein shared 94% amino acid identity with the A2 G protein. In contrast, the 18537 G protein shared only 53% amino acid identity with the A2 sequence; interestingly, most of the sequence divergence occurred in the proposed extracellular domain of the G protein. This extensive divergence for the G protein was significantly greater than that observed for other

Summary Vaccines prevent infectious disease largely by inducing protective neutralizing antibodies against vulnerable epitopes. Multiple major pathogens have resisted traditional vaccine development, although vulnerable epitopes targeted by neutralizing antibodies have been identified for several such cases. Hence, new vaccine design methods to induce epitope-specific neutralizing antibodies are needed. Here we show, with a neutralization epitope from respiratory syncytial virus (RSV), that computational protein design can generate small, thermally and conformationally stable protein scaffolds that accurately mimic the viral epitope structure and induce potent neutralizing antibodies. These scaffolds represent promising leads for research and development of a human RSV vaccine needed to protect infants, young children and the elderly. More generally, the results provide proof of principle for epitope-focused and scaffold-based vaccine design, and encourage the evaluation and further development of these strategies for a variety of other vaccine targets including antigenically highly variable pathogens such as HIV and influenza.

The ancestors of the human immunodeficiency viruses (HIV-1 and HIV-2) may have evolved from a reservoir of African nonhuman primate lentiviruses, termed simian immunodeficiency viruses (SIV). None of the SIV strains characterized so far are closely related to HIV-1. HIV-2, however, is closely related to SIV (SIVmac) isolated from captive rhesus macaques (Macaca mulatta). SIV infection of feral Asian macaques has not been demonstrated by serological surveys. Thus, macaques may have acquired SIV in captivity by cross-species transmission from an SIV-infected African primate. Sooty mangabeys (Cercocebus atys), an African primate species indigenous to West Africa, however, are infected with SIV (SIVsm) both in captivity and in the wild (P. Fultz, personal communication). We have molecularly cloned and sequenced SIVsm and report here that it is closely related to SIVmac and HIV-2. These results suggest that SIVsm has infected macaques in captivity and humans in West Africa and evolved as SIVmac and HIV-2, respectively.

Based on a quantum analysis of two capacitively coupled current-biased Josephson junctions, we propose two fundamental two-qubit quantum logic gates. Each of these gates, when supplemented by single-qubit operations, is sufficient for universal quantum computation. Numerical solutions of the time-dependent Schrödinger equation demonstrate that these operations can be performed with good fidelity. The current-biased Josephson junction is an easily fabricated device with great promise as a scalable solid-state qubit [1], as demonstrated by the recent observations of Rabi oscillations [2,3]. This phase qubit is controlled through manipulation of the bias currents and application of microwave pulses resonant with the energy level splitting [2].In this Letter we analyze the quantum dynamics of two coupled phase qubits. (The classical dynamics of this system has also been studied recently [4]). We identify two quantum logic gates that, together with single-qubit operations, provide all necessary ingredients for a universal quantum computer. We perform full dynamical simulations of these gates through numerical integration of the time-dependent Schrödinger equation. These two-qubit operations may be experimentally probed with the methods already used to observe single junction Rabi oscillations [2,3]. Such experiments are of fundamental importance: the successful demonstration of macroscopic quantum entanglement holds profound implications for the universal validity of quantum mechanics [5]. Important progress toward this goal are the temporal oscillations of coupled charge qubits [6] and spectroscopic measurements [7] on the system considered here. Finally, our methods are applicable to the other promising superconducting proposals based on charge, flux, and hybrid realizations [8].Figure 1(a) shows the circuit diagram of our coupled qubits. Each junction has characteristic capacitance C J and critical current I c , and they are coupled by capacitance C C . The two degrees of freedom of this system are the phase differences γ 1 and γ 2 , with dynamics governed by the Hamiltonian [9]Here we have employed the charging and Josephson energies E C = e 2 /2C J and E J = I c /2e, the normalized bias currents J 1 = I 1 /I c , J 2 = I 2 /I c , and the dimensionless coupling parameter ζ = C C /(C C + C J ). This coupling scheme has been recently analyzed [9, 10, 11] and results in a system with easily tuned energy levels and adjustable effective coupling. While ζ is typically fixed by fabrication, the energy levels and the effective coupling of the associated eigenstates are under experimental control through J 1 and J 2 . As shown below, the two junctions are decoupled for J 1 and J 2 sufficiently different, but if J 1 and J 2 are related in certain ways, the junctions are maximally coupled. To illustrate this method of control, we define a reference bias current J 0 and consider the variation of J 1 and J 2 through a detuning parameter ǫ:Quantum logic gates are implemented by varying ǫ with time as shown in Fig. 1(b). This ra...

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We present spectroscopic evidence for the creation of entangled macroscopic quantum states in two current-biased Josephson-junction qubits coupled by a capacitor. The individual junction bias currents are used to control the interaction between the qubits by tuning the energy level spacings of the junctions in and out of resonance with each other. Microwave spectroscopy in the 4 to 6 gigahertzrange at 20 millikelvin reveals energy levels that agree well with theoretical results for entangled states. The single qubits are spatially separate, and the entangled states extend over the 0.7-millimeter distance between the two qubits.

The holy grail for HIV vaccine development is an immunogen that elicits persisting antibodies with broad neutralizing activity against field strains of the virus. Unfortunately, very little progress has been made in finding or designing such immunogens. Using the SIV model, we have taken a markedly different approach: delivery of an adeno-associated virus (AAV) gene transfer vector to muscle for the expression of antibodies or antibody-like immunoadhesins having predetermined anti-SIV specificity. With this approach, anti-SIV molecules are endogenously synthesized in myofibers and passively distributed to the circulatory system. Using such an approach in monkeys, we have now generated long-lasting neutralizing activity in serum and observed complete protection against intravenous challenge with virulent SIV. In essence, this strategy bypasses the adaptive immune system and holds significant promise as a novel approach to an effective HIV vaccine.

The transport of colloids in geochemically heterogeneous porous media is investigated. A model describing the transport and deposition of colloids onto heterogeneously charged mineral grains is developed and applied to column experiments. The model characterizes mineral grain surfaces according to a patchwise charge distribution, with individual patches being either favorable or unfavorable for deposition depending on their electrostatic charge. Separate rate expressions are used in the model to depict favorable and unfavorable deposition kinetics. Declining deposition kinetics that are produced when previously retained particles block subsequent attachment of colloids are quantified in the model by dynamic blocking functions. Column experiments involving colloid transport in geochemically heterogeneous porous media were performed using silica colloids and quartz sand. Surface charge heterogeneity was introduced into the porous medium by coating a fraction of the quartz sand with iron oxyhydroxide. Theoretical breakthrough curves generated by the model using experimentally determined parameters compared quite well to the experimental results, demonstrating the importance of geochemically heterogeneous surfaces in determining the transport behavior of colloidal particles in heterogeneous aquatic environments.