Phenotypic hypersusceptibility to multiple protease inhibitors and low replicative capacity in patients who are chronically infected with human immunodeficiency virus type 1

Increased susceptibility to the protease inhibitors saquinavir and amprenavir has been observed in human immunodeficiency virus type 1 (HIV-1) with specific mutations in protease (V82T and N88S). Increased susceptibility to ritonavir has also been described in some viruses from antiretroviral agent-naïve patients with primary HIV-1 infection in association with combinations of amino acid changes at polymorphic sites in the protease. Many of the viruses displaying increased susceptibility to protease inhibitors also had low replication capacity. In this retrospective study, we analyze the drug susceptibility phenotype and the replication capacity of virus isolates obtained at the peaks of viremia during five consecutive structured treatment interruptions in 12 chronically HIV-1-infected patients. Ten out of 12 patients had at least one sample with protease inhibitor hypersusceptibility (change ≤0.4-fold) to one or more protease inhibitor. Hypersusceptibility to different protease inhibitors was observed at variable frequency, ranging from 38% to amprenavir to 11% to nelfinavir. Pairwise comparisons between susceptibilities for the protease inhibitors showed a consistent correlation among all pairs. There was also a significant relationship between susceptibility to protease inhibitors and replication capacity in all patients. Replication capacity remained stable over the course of repetitive cycles of structured treatment interruptions. We could find no association between in vitro replication capacity and in vivo plasma viral load doubling time and CD4(+) and CD8(+) T-cell counts at each treatment interruption. Several mutations were associated with hypersusceptibility to each protease inhibitor in a univariate analysis. This study extends the association between hypersusceptibility to protease inhibitors and low replication capacity to virus isolated from chronically infected patients and highlights the complexity of determining the genetic basis of this phenomenon. The potential clinical relevance of protease inhibitor hypersusceptibility and low replication capacity to virologic response to protease inhibitor-based therapies deserves to be investigated further

Currents, Torques, and Polarization Factors in Magnetic Tunnel Junctions

Application of Bardeen's tunneling theory to magnetic tunnel junctions having a general degree of atomic disorder reveals the close relationship between magneto-conduction and voltage-driven pseudo-torque, as well as the thickness dependence of tunnel-polarization factors. Among the results: 1) The torque generally varies as sin theta at constant applied voltage. 2) Whenever polarization factors are well defined, the voltage-driven torque on each moment is uniquely proportional to the polarization factor of the other magnet. 3) At finite applied voltage, this relation predicts significant voltage-asymmetry in the torque. For one sign of voltage the torque remains substantial even when the magnetoconductance is greatly diminished. 4) A broadly defined junction model, called ideal middle, allows for atomic disorder within the magnets and F/I interface regions. In this model, the spin dependence of a state-weighting factor proportional to the sum over general state index of evaluated within the (e.g. vacuum) barrier generalizes the local state density in previous theories of the tunnel-polarization factor. 5) For small applied voltage, tunnel-polarization factors remain legitimate up to first order in the inverse thickness of the ideal middle. An algebraic formula describes the first-order corrections to polarization factors in terms of newly defined lateral auto-correllation scales.Comment: This version no. 3 is thoroughly revised for clarity. Just a few notations and equations are changed, and references completed. No change in results. 17 pages including 4 figure

Carbon Dioxide Dynamics During a Growing Season in Midwestern Cropping Systems

Daily and seasonal CO2-exchange dynamics between the boundary layer and biosphere is important to understanding Net Ecosystem Exchange of terrestrial ecosystems. Spatial and temporal variations of CO2 fluxes across midwestern cropping systems have not been well documented. This study was designed to monitor and evaluate spatial and temporal dynamics of CO2 exchange across a watershed region for typical production fields of corn (Zea mays L.) and soybean [Glycine max (L.) Merr.] in the Midwest by quantifying the above-canopy, within-canopy, and soil components of C balance for this cropping system. An energy-balance approach using eddy covariance was utilized across different fields making year-around measurements in both corn and soybean fields to quantify the exchange of CO2 and H2O between the crop canopy and the atmospheric boundary layer. Within-canopy concentrations of CO2 and H2O vapor were measured with an eight-port CO2/H2O infrared analyzer. Soil respiration was quantified using soil chambers at various landscape positions throughout the growing season. Fluxes of CO2 and H2O vapor throughout the day were dependent on net radiation and the stage of canopy development. Diurnal variations in CO2 and H2O vapor fluxes revealed that the magnitude of the fluxes is large and the variation of the fluxes among fields was consistent throughout the season. Integration of the daily fluxes into seasonal totals showed large differences among crops and fields. Flux differences were the result of the effect of varying soil types on water-holding capacity. Seasonal integrated values were lower than estimates derived from biomass samples collected within the fields and the measurement of the C content of the biomass. Within-canopy recycling of soil CO2 may provide insight to this discrepancy. The techniques are available to quantify the CO2 and H2O vapor fluxes across different management systems and landscapes to help refine our understanding of the magnitude of the CO2 and H2O dynamics in cropping systems

Entangling two Bose Einstein condensates in a double cavity system

We propose a scheme to transfer the quantum state of light fields to the collective density excitations of a Bose Einstein condensate (BEC) in a cavity. This scheme allows to entangle two BECs in a double cavity setup by transferring the quantum entanglement of two light fields produced from a nondegenerate parametric amplifier (NOPA) to the collective density excitations of the two BECs. An EPR state of the collective density excitations can be created by a judicious choice of the system parameters.Comment: 3 figure

Direct imaging of structural changes induced by ionic liquid gating leading to engineered three-dimensional meso-structures

The controlled transformation of materials, both their structure and their physical properties, is key to many devices. Ionic liquid gating can induce the transformation of thin-film materials over long distances from the gated surface. Thus, the mechanism underlying this process is of considerable interest. Here we directly image, using in situ, real-time, high-resolution transmission electron microscopy, the reversible transformation between the oxygen vacancy ordered phase brownmillerite SrCoO2.5 and the oxygen ordered phase perovskite SrCoO3. We show that the phase transformation boundary moves at a velocity that is highly anisotropic, traveling at speeds ~30 times faster laterally than through the thickness of the film. Taking advantage of this anisotropy, we show that three-dimensional metallic structures such as cylinders and rings can be realized. Our results provide a roadmap to the construction of complex meso-structures from their exterior surfaces

Global Research Alliance N2O chamber methodology guidelines: Design considerations

Terrestrial ecosystems, both natural ecosystems and agroecosystems, generate greenhouse gases (GHGs). The chamber method is the most common method to quantify GHG fluxes from soil–plant systems and to better understand factors affecting their generation and mitigation. The objective of this study was to review and synthesize literature on chamber designs (non‐flow‐through, non‐steady‐state chamber) and associated factors that affect GHG nitrous oxide (N2O) flux measurement when using chamber methods. Chamber design requires consideration of many facets that include materials, insulation, sealing, venting, depth of placement, and the need to maintain plant growth and activity. Final designs should be tailored, and bench tested, in order to meet the nuances of the experimental objectives and the ecosystem under study while reducing potential artifacts. Good insulation, to prevent temperature fluctuations and pressure changes, and a high‐quality seal between base and chamber are essential. Elimination of pressure differentials between headspace and atmosphere through venting should be performed, and designs now exist to eliminate Venturi effects of earlier tube‐type vent designs. The use of fans within the chamber headspace increases measurement precision but may alter the flux. To establish best practice recommendations when using fans, further data are required, particularly in systems containing tall plants, to systematically evaluate the effects that fan speed, position, and mixing rate have on soil gas flux.Peer reviewe