Complex interplay of kinetic factors governs the synergistic properties of HIV-1 entry inhibitors.

The homotrimeric HIV-1 envelope glycoprotein (Env) undergoes receptor-triggered structural changes that mediate viral entry through membrane fusion. This process is inhibited by chemokine receptor antagonists (CoRAs) that block Env-receptor interactions and by fusion inhibitors (FIs) that disrupt Env conformational transitions. Synergy between CoRAs and FIs has been attributed to a CoRA-dependent decrease in the rate of viral membrane fusion that extends the lifetime of the intermediate state targeted by FIs. Here, we demonstrated that the magnitude of CoRA/FI synergy unexpectedly depends on FI-binding affinity and the stoichiometry of chemokine receptor binding to trimeric Env. For C-peptide FIs (clinically represented by enfuvirtide), synergy waned as binding strength decreased until inhibitor combinations behaved additively. Curiously, this affinity dependence on synergy was absent for 5-Helix-type FIs. We linked this complex behavior to the CoRA dependence of Env deactivation following FI binding. For both FI classes, reducing chemokine receptor levels on target cells or eliminating competent chemokine receptor-binding sites on Env trimers resulted in a loss of synergistic activity. These data imply that the stoichiometry required for CoRA/FI synergy exceeds that required for HIV-1 entry. Our analysis suggests two distinct roles for chemokine receptor binding, one to trigger formation of the FI-sensitive intermediate state and another to facilitate subsequent conformational transitions. Together, our results could explain the wide variety of previously reported activities for CoRA/FI combinations. These findings also have implications for the combined use of CoRAs and FIs in antiviral therapies and point to a multifaceted role for chemokine receptor binding in promoting HIV-1 entry

Capacity of classes of Gaussian channels. Part I - Discrete-time

Capacity of discrete time Gaussian channel

Large transport landing characteristics as simulated in flight and on the ground

Comparison of theoretical and simulated low speed landing characteristics for large transport aircraft

Mirror Gazing for Cultural Bereavement: A Mixed-Methods Study into the Impact of a Restricted Sensory Environment Meditation Process (Psychomanteum) on Culture Shock in Expatriates

Thirteen expatriates experienced an individual 2-3 hour psychomanteum process, including pre- and post-meditation interviews based on cultural bereavement theory, mirror gazing in a restricted sensory chamber, art work, and follow-up surveys. Repeated measures of negative affect were administered at pretest, posttest, and follow-up periods. Correlational analyses revealed significant reductions in total culture shock and mood disturbance at follow up. Extraversion, home country, and importance of religion/ spirituality were significant covariates in change on total culture shock scores at posttest. Qualitative analyses revealed four categories of effects: clarified emotional conflicts, letting go, shifted perspectives, and reviewed success factors. The psychomanteum process could be used with talk therapy techniques and support groups for expatriates to facilitate cultural adjustment and improve quality of life abroad

Investigations in space communications theory, including topics related to random processes, filtering, telemetry Semiannual status report, 1 Oct. 1966 - 31 Mar. 1967

Random processes, filtering, and telemetry problems in space communications theor

Proposal for a study of computer mapping of terrain using multispectral data from ERTS-A for the Yellowstone National Park test site

The author has identified the following significant results. A terrain map of Yellowstone National Park showed plant community types and other classes of ground cover in what is basically a wild land. The map comprised 12 classes, six of which were mapped with accuracies of 70 to 95%. The remaining six classes had spectral reflectances that overlapped appreciably, and hence, those were mapped less accurately. Techniques were devised for quantitatively comparing the recognition map of the park with control data acquired from ground inspection and from analysis of sidelooking radar images, a thermal IR mosaic, and IR aerial photos of several scales. Quantitative analyses were made in ten 40 sq km test areas. Comparison mechanics were performed by computer with the final results displayed on line printer output. Forested areas were mapped by computer using ERTS data for less than 1/4 the cost of the conventional forest mapping technique for topographic base maps