Oral abstracts of the 21st International AIDS Conference 18-22 July 2016, Durban, South Africa

The rate at which HIV-1 infected individuals progress to AIDS is highly variable and impacted by T cell immunity. CD8 T cell inhibitory molecules are up-regulated in HIV-1 infection and associate with immune dysfunction. We evaluated participants (n=122) recruited to the SPARTAC randomised clinical trial to determine whether CD8 T cell exhaustion markers PD-1, Lag-3 and Tim-3 were associated with immune activation and disease progression.Expression of PD-1, Tim-3, Lag-3 and CD38 on CD8 T cells from the closest pre-therapy time-point to seroconversion was measured by flow cytometry, and correlated with surrogate markers of HIV-1 disease (HIV-1 plasma viral load (pVL) and CD4 T cell count) and the trial endpoint (time to CD4 count <350 cells/μl or initiation of antiretroviral therapy). To explore the functional significance of these markers, co-expression of Eomes, T-bet and CD39 was assessed.Expression of PD-1 on CD8 and CD38 CD8 T cells correlated with pVL and CD4 count at baseline, and predicted time to the trial endpoint. Lag-3 expression was associated with pVL but not CD4 count. For all exhaustion markers, expression of CD38 on CD8 T cells increased the strength of associations. In Cox models, progression to the trial endpoint was most marked for PD-1/CD38 co-expressing cells, with evidence for a stronger effect within 12 weeks from confirmed diagnosis of PHI. The effect of PD-1 and Lag-3 expression on CD8 T cells retained statistical significance in Cox proportional hazards models including antiretroviral therapy and CD4 count, but not pVL as co-variants.Expression of ‘exhaustion’ or ‘immune checkpoint’ markers in early HIV-1 infection is associated with clinical progression and is impacted by immune activation and the duration of infection. New markers to identify exhausted T cells and novel interventions to reverse exhaustion may inform the development of novel immunotherapeutic approaches

Dielectric and structural properties of aqueous nonpolar solute mixtures

The dielectric properties and molecular structure of water mixtures with different nonpolar solutes (methane and noble gases) are studied using molecular dynamics. The water-water, water-solute, and solute-solute interactions are calculated using the combination of a polarizable potential [J. Li, Z. Zhou, and R. J. Sadus, J. Chem. Phys. 127, 154509 (2007)] for water plus the Lennard-Jones potential. The effect of solute size and concentration on the solubility of the system, hydrogen bonding, dielectric constant, and dipole moment are investigated over a temperature range of 278-750 K and solute percentage mole fractions up to 30%. Solute particles affect the structure of water, resulting in the compression of oxygen-oxygen and oxygen-hydrogen radial distribution functions. The influence of the solute extends both to relatively low concentrations and high temperatures. The coordination numbers of aqueous solutions of the nonpolar solutes appear to be proportional to the size of the solute particles. Our study shows the destructive influence of the nonpolar solute on both the tetrahedral water structure and hydrogen bond formation at solute concentrations greater than 30%. The presence of nonpolar particles typically decreases both the dielectric constant and dipole moment. The decrease of dielectric constant and water dipole moment is directly proportional to the solute concentration and temperature

Research of interaction of a natural and forced convection in a vortex chamber of the chemical reactor

In this paper, a chemical reactor for producing refractory metals was considered. A physical and mathematical model of fluid motion and heat transfer in a vortex chamber of the chemical reactor under forced and free convection has been described and simulated. The numerical simulation was carried out in “velocity–pressure” variables by using an alternating direction implicit scheme. The velocity field and the temperature distribution in the reactor were obtained. Parametric studies on effects of the Reynolds, Prandtl and Rossbi criteria on the flow characteristics were also performed. The graphs presented show that natural convection has a significant impact on the hydrodynamics of the flow and intensifies the heat transfer. Reliability of the calculations was verified by comparing the results obtained by another method

Thermodynamic properties and diffusion of water + methane binary mixtures

Thermodynamic and diffusion properties of water + methane mixtures in a single liquid phase are studied using NVT molecular dynamics. An extensive comparison is reported for the thermal pressure coefficient, compressibilities, expansion coefficients, heat capacities, Joule-Thomson coefficient, zero frequency speed of sound, and diffusion coefficient at methane concentrations up to 15% in the temperature range of 298-650 K. The simulations reveal a complex concentration dependence of the thermodynamic properties of water + methane mixtures. The compressibilities, heat capacities, and diffusion coefficients decrease with increasing methane concentration, whereas values of the thermal expansion coefficients and speed of sound increase. Increasing methane concentration considerably retards the self-diffusion of both water and methane in the mixture. These effects are caused by changes in hydrogen bond network, solvation shell structure, and dynamics of water molecules induced by the solvation of methane at constant volume conditions

Atomistic water models: Aqueous thermodynamic properties from ambient to supercritical conditions

Progress in obtaining an accurate atomistic model for water is reviewed and evaluated with particular attention to thermodynamic properties such as the thermal pressure coefficient, thermal expansion coefficient, isothermal and adiabatic compressibilities, isobaric and isochoric heat capacities, Joule–Thomson coefficient, speed of sound and vapor–liquid equlibria. The different multi-site models are categorised in terms of bond rigidity/flexibility and polarization. The models are assessed for their ability to reproduce experimental values at conditions ranging from ambient to supercritical conditions. In general, three or four sites are sufficient to obtain reasonable results with the addition of more sites not consistently yielding improvements. The addition of bond flexibility, while improving agreement with experiment for such properties as phase coexistence, dielectric constants, viscosity and diffusion, does not appear to significantly improve the prediction of thermodynamic properties in general. For the supercritical heat capacities and thermal expansion coefficient the flexible TIP4P/2005f model yields less accurate values than its rigid TIP4P/2005 counterpart. In contrast, accounting for polarizability consistently results in improved agreement with experiment. For properties such as the isochoric heat capacity and thermal expansion coefficient, the polarizable MCYna model yields values that are in very close agreement with experimental data in the temperature range of 300–600 K. A quantitative ranking scheme is proposed and applied to ambient conditions. At or near ambient conditions, the overall ranking of models investigated is (iAMOEBA, MCYna) > (BKd3, TIP4P/FQ, GCPM, BK3) > (TIP4P/2005, SPC/Fw, SPC/E) > (SPC, TIP4P/2005f, NvdE, TIP5P) > (TIP4P, TIP3P) > (MCY, MCYL)