Longitudinal Study of Primary HIV-1 Isolates in Drug-Naïve Individuals Reveals the Emergence of Variants Sensitive to Anti-HIV-1 Monoclonal Antibodies

To study how virus evolution affects neutralization sensitivity and to determine changes that occur in and around epitopes, we tested the ability of 13 anti-HIV-1 gp120 (anti-V2, anti-V3, anti-CD4bd and anti-carbohydrate) human monoclonal antibodies (mAbs) to neutralize sequential viruses obtained from five HIV-1 chronically infected drug naïve individuals. Overall, primary viruses collected from patients at first visit were resistant to neutralization by all anti-HIV-1 mAbs with the exception of one virus sensitive to IgG1b12. Four of the five patients' viruses evolved increased sensitivity to neutralization by anti-V3 mAbs. Virus collected from a patient obtained 31 months later, evolved increased sensitivity to anti-V2, anti-V3, and anti-CD4bd mAbs. Furthermore, the anti-V2 and anti-CD4bd mAbs also exhibited increased neutralization capacities against virus collected from a patient 29 months later. Of the seven anti-V3 mAbs, five showed increased potency to neutralize the evolved virus from a patient collected after 11 months, and three exhibited increased potency against viruses from two patients collected 29 and 36 months later. Anti-V3 mAbs exhibited the most breadth and potency in neutralizing the evolving viruses. Sequence analysis of the envelope regions revealed amino acid conservation within the V3 loop, while most of the changes identified occurred outside the core epitopes and in particular within the C3 region; these may account for increased neutralization sensitivity. These studies demonstrate that in vivo, HIV-1 can evolve increased neutralization sensitivity to mAbs and that the spectrum of neutralization capacities by mAbs can be broader when studied in longitudinal analysis

The effects of magnetic field on the d-density wave order in the cuprates

We consider the effects of a perpendicular magnetic field on the d-density wave order and conclude that if the pseudogap phase in the cuprates is due to this order, then it is highly insensitive to the magnetic field in the underdoped regime, while its sensitivity increases as the gap vanishes in the overdoped regime. This appears to be consistent with the available experiments and can be tested further in neutron scattering experiments. We also investigate the nature of the de Haas- van Alphen effect in the ordered state and discuss the possibility of observing it.Comment: 5 pages, 4 eps figures, RevTex4. Corrected a silly but important typo in the abstrac

Different Pattern of Immunoglobulin Gene Usage by HIV-1 Compared to Non-HIV-1 Antibodies Derived from the Same Infected Subject

A biased usage of immunoglobulin (Ig) genes is observed in human anti-HIV-1 monoclonal antibodies (mAbs) resulting probably from compensation to reduced usage of the VH3 family genes, while the other alternative suggests that this bias usage is due to antigen requirements. If the antigen structure is responsible for the preferential usage of particular Ig genes, it may have certain implications for HIV vaccine development by the targeting of particular Ig gene-encoded B cell receptors to induce neutralizing anti-HIV-1 antibodies. To address this issue, we have produced HIV-1 specific and non-HIV-1 mAbs from an infected individual and analyzed the Ig gene usage. Green-fluorescence labeled virus-like particles (VLP) expressing HIV-1 envelope (Env) proteins of JRFL and BaL and control VLPs (without Env) were used to select single B cells for the production of 68 recombinant mAbs. Ten of these mAbs were HIV-1 Env specific with neutralizing activity against V3 and the CD4 binding site, as well as non-neutralizing mAbs to gp41. The remaining 58 mAbs were non-HIV-1 Env mAbs with undefined specificities. Analysis revealed that biased usage of Ig genes was restricted only to anti-HIV-1 but not to non-HIV-1 mAbs. The VH1 family genes were dominantly used, followed by VH3, VH4, and VH5 among anti-HIV-1 mAbs, while non-HIV-1 specific mAbs preferentially used VH3 family genes, followed by VH4, VH1 and VH5 families in a pattern identical to Abs derived from healthy individuals. This observation suggests that the biased usage of Ig genes by anti-HIV-1 mAbs is driven by structural requirements of the virus antigens rather than by compensation to any depletion of VH3 B cells due to autoreactive mechanisms, according to the gp120 superantigen hypothesis

A New Look At Carbon Abundances In Planetary Nebulae. IV. Implications For Stellar Nucleosynthesis

This paper is the fourth and final report on a project designed to study carbon abundances in a sample of planetary nebulae representing a broad range in progenitor mass and metallicity. We present newly acquired optical spectrophotometric data for three Galactic planetary nebulae IC 418, NGC 2392, and NGC 3242 and combine them with UV data from the IUE Final Archive for identical positions in each nebula to determine accurate abundances of He, C, N, O, and Ne at one or more locations in each object. We then collect abundances of these elements for the entire sample and compare them with theoretical predictions of planetary nebula abundances from a grid of intermediate mass star models. We find some consistency between observations and theory, lending modest support to our current understanding of nucleosynthesis in stars below 8 M_o in birth mass. Overall, we believe that observed abundances agree with theoretical predictions to well within an order of magnitude but probably not better than within a factor of 2 or 3. But even this level of consistency between observation and theory enhances the validity of published intermediate-mass stellar yields of carbon and nitrogen in the study of the abundance evolution of these elements.Comment: 41 pages, 11 figures. Accepted for publication in the Astrophysical Journa

The physical parameters, excitation and chemistry of the rim, jets and knots of the planetary nebula NGC 7009

We present long-slit optical spectra along the major axis of the planetary nebula NGC 7009. These data allow us to discuss the physical, excitation and chemical properties of all the morphological components of the nebula, including its remarkable systems of knots and jets. The main results of this analysis are the following: i) the electron temperature throughout the nebula is remarkably constant, T_e[OIII] = 10200K; ii) the bright inner rim and inner pair of knots have similar densities of N_e = 6000cm^{-3}, whereas a much lower density of N_e = 1500cm^{-3} is derived for the outer knots as well as for the jets; iii) all the regions (rim, inner knots, jets and outer knots) are mainly radiatively excited; and iv) there are no clear abundance changes across the nebula for He, O, Ne, or S. There is a marginal evidence for an overabundance of nitrogen in the outer knots (ansae), but the inner ones (caps) and the rim have similar N/H values that are at variance with previous results. Our data are compared to the predictions of theoretical models, from which we conclude that the knots at the head of the jets are not matter accumulated during the jet expansion through the circumstellar medium, neither can their origin be explained by the proposed HD or MHD interacting-wind models for the formation of jets/ansae, since the densities as well as the main excitation mechanisms of the knots, disagree with model predictions.Comment: Figure 1 was changed because features were misidentified in the previous version. 17 pages including 5 figures and 3 tables. ApJ in press. Also available at http://www.iac.es/galeria/denise

Magnetic field independence of the spin gap in YBa_2Cu_3O_{7-delta}

We report, for magnetic fields of 0, 8.8, and 14.8 Tesla, measurements of the temperature dependent ^{63}Cu NMR spin lattice relaxation rate for near optimally doped YBa_2Cu_3O_{7-delta}, near and above T_c. In sharp contrast with previous work we find no magnetic field dependence. We discuss experimental issues arising in measurements of this required precision, and implications of the experiment regarding issues including the spin or pseudo gap.Comment: 4 pages, 3 figures, as accepted for publication in Physical Review Letter