Activation of a dendritic cell–T cell axis by Ad5 immune complexes creates an improved environment for replication of HIV in T cells

The STEP HIV vaccine trial, which evaluated a replication-defective adenovirus type 5 (Ad5) vector vaccine, was recently stopped. The reasons for this included lack of efficacy of the vaccine and a twofold increase in the incidence of HIV acquisition among vaccinated recipients with increased Ad5-neutralizing antibody titers compared with placebo recipients. To model the events that might be occurring in vivo, the effect on dendritic cells (DCs) of Ad5 vector alone or treated with neutralizing antiserum (Ad5 immune complexes [IC]) was compared. Ad5 IC induced more notable DC maturation, as indicated by increased CD86 expression, decreased endocytosis, and production of tumor necrosis factor and type I interferons. We found that DC stimulation by Ad5 IC was mediated by the Fcγ receptor IIa and Toll-like receptor 9 interactions. DCs treated with Ad5 IC also induced significantly higher stimulation of Ad5-specific CD8 T cells equipped with cytolytic machinery. In contrast to Ad5 vectors alone, Ad5 IC caused significantly enhanced HIV infection in DC–T cell cocultures. The present results indicate that Ad5 IC activates a DC–T cell axis that, together with the possible persistence of the Ad5 vaccine in seropositive individuals, may set up a permissive environment for HIV-1 infection, which could account for the increased acquisition of HIV-1 infection among Ad5 seropositive vaccine recipients

Activation of a dendritic cell–T cell axis by Ad5 immune complexes creates an improved environment for replication of HIV in T cells

The STEP HIV vaccine trial, which evaluated a replication-defective adenovirus type 5 (Ad5) vector vaccine, was recently stopped. The reasons for this included lack of efficacy of the vaccine and a twofold increase in the incidence of HIV acquisition among vaccinated recipients with increased Ad5-neutralizing antibody titers compared with placebo recipients. To model the events that might be occurring in vivo, the effect on dendritic cells (DCs) of Ad5 vector alone or treated with neutralizing antiserum (Ad5 immune complexes [IC]) was compared. Ad5 IC induced more notable DC maturation, as indicated by increased CD86 expression, decreased endocytosis, and production of tumor necrosis factor and type I interferons. We found that DC stimulation by Ad5 IC was mediated by the Fcγ receptor IIa and Toll-like receptor 9 interactions. DCs treated with Ad5 IC also induced significantly higher stimulation of Ad5-specific CD8 T cells equipped with cytolytic machinery. In contrast to Ad5 vectors alone, Ad5 IC caused significantly enhanced HIV infection in DC–T cell cocultures. The present results indicate that Ad5 IC activates a DC–T cell axis that, together with the possible persistence of the Ad5 vaccine in seropositive individuals, may set up a permissive environment for HIV-1 infection, which could account for the increased acquisition of HIV-1 infection among Ad5 seropositive vaccine recipients

A Method for Simultaneous Optimisation of Orbit and Dispersion in Storage Rings

An algorithm for the simultaneous optimisation of orbit and dispersion in a storage ring is presented. Based on orbit and dispersion measurements the algorithm determines the optimal corrector settings in order to simultaneously minimize the r.m.s orbit, the r.m.s dispersion and the r.m.s strenght of the dipoles correctors. A number of different options for error handling of beam position monitors, weighting, and correction have been introduced to ensure the stability of the algorithm in the environment of a large accelerator. Experimental results are presented for the LEP collider demonstrating the efficiency of the method. The use of this correction algorithm for LEP in 1999 allowed achieving about a factor of two smaller vertical emittances than in previous years

Magnetic Monopoles in Ferromagnetic Spin-Triplet Superconductors

Using the $\phi$-mapping method, we argue that ferromagnetic spin-triplet superconductors allow formation of unstable magnetic monopoles. In particular, we show that the limit points and the bifurcation points of the $\phi$-mapping will serve as the interaction points of these magnetic monopoles.Comment: 4 pages, no figure

Integrating cogeneration and intermittent waste-heat recovery in food processing: Microturbines vs. ORC systems in the coffee roasting industry

Coffee roasting is a highly energy intensive process wherein a large quantity of heat is discharged from the stack at medium-to-high temperatures. Much of the heat is released from the afterburner, which is required to remove volatile organic compounds and other pollutants from the flue gases. In this work, intermittent waste-heat recovery via thermal energy storage (TES) and organic Rankine cycles (ORCs) is compared to combined heat and power (CHP) based on micro gas-turbines (MGTs) for a coffee roasting plant. With regard to the former, a promising solution is proposed that involves recovering waste heat from the flue gas stream by partial hot-gas recycling at the rotating drum coffee roaster, and coupling this to a thermal store and an ORC engine for power generation. The two solutions (CHP + MGT prime mover vs. waste-heat recovery + ORC engine) are investigated based on mass and energy balances, and a cost assessment methodology is adopted to compare the profitability of three system configurations integrated into the selected roasting process. The case study involves a major Italian roasting plant with a 3,000 kg per hour coffee production capacity. Three options are investigated: (i) intermittent waste-heat recovery from the hot flue-gases with an ORC engine coupled to a TES system; (ii) regenerative topping MGT coupled to the existing modulating gas burner to generate hot air for the roasting process; and (iii) non-regenerative topping MGT with direct recovery of the turbine outlet air for the roasting process. The results show that the profitability of these investments is highly influenced by the natural gas and electricity prices and by the coffee roasting production capacity. The CHP solution via an MGT appears as a more profitable option than waste-heat recovery via an ORC engine primarily due to the intermittency of the heat-source availability and the high electricity cost relative to the cost of natural gas

Proposal to Increase the LEP Energy with Horizontal Orbit Correctors

In an e+ e- collider the beam energy depends only on the bending field integral "Bds while the synchrotron radiation power scales with "B2ds and is sensitive to the details of the field distribution. With fixed RF acceleration voltage it is thus possible to attain higher energies by increasing the effective bending magnet length. We propose to use the horizontal orbit correctors to exploit this effect. To control the orbit perturbations, 79 unused correctors in the regular arcs and 14 unused correctors in the dispersion suppressors will have to be powered. An energy increase of approximatively 0.18 GeV per beam might be obtained

Identification and visualization of multidimensional antigen-specific T-cell populations in polychromatic cytometry data.

An important aspect of immune monitoring for vaccine development, clinical trials, and research is the detection, measurement, and comparison of antigen-specific T-cells from subject samples under different conditions. Antigen-specific T-cells compose a very small fraction of total T-cells. Developments in cytometry technology over the past five years have enabled the measurement of single-cells in a multivariate and high-throughput manner. This growth in both dimensionality and quantity of data continues to pose a challenge for effective identification and visualization of rare cell subsets, such as antigen-specific T-cells. Dimension reduction and feature extraction play pivotal role in both identifying and visualizing cell populations of interest in large, multi-dimensional cytometry datasets. However, the automated identification and visualization of rare, high-dimensional cell subsets remains challenging. Here we demonstrate how a systematic and integrated approach combining targeted feature extraction with dimension reduction can be used to identify and visualize biological differences in rare, antigen-specific cell populations. By using OpenCyto to perform semi-automated gating and features extraction of flow cytometry data, followed by dimensionality reduction with t-SNE we are able to identify polyfunctional subpopulations of antigen-specific T-cells and visualize treatment-specific differences between them

Computer-aided working-fluid design, thermodynamic optimisation and technoeconomic assessment of ORC systems for waste-heat recovery

The wider adoption of organic Rankine cycle (ORC) technology can be facilitated by improved thermodynamic performance and reduced costs. In this context the power system should be evaluated based on a thermeconomic assessment with the aim of improving economic viability. This paper couples the computer- aided molecular design (CAMD) of the working-fluid with thermodynamic modelling and optimisation, in addition to heat-exchanger sizing models, component cost correlations, and a thermoeconomic assessment. The proposed CAMD-ORC framework, based on the SAFT-γ Mie equation of state, allows the thermodynamic optimisation of the cycle and working-fluid in a single stage, thus removing subjective and pre-emptive screening criteria that would otherwise exist in conventional studies. Following validation, the framework is used to identify optimal working-fluids for three different heat sources (150, 250 and 350 °C), corresponding to small- to medium-scale applications. In each case, the optimal combination of working-fluid and ORC system is identified, and investment costs are evaluated. It is observed that fluids with low specific-investment costs (SIC) are different to those that maximise power output. The fluids with the lowest SIC are isoheptane, 2-pentene and 2-heptene, with SICs of 5,620, 2,760 and 2,070 £/kW respectively, and corresponding power outputs of 32.9, 136.6 and 213.9 kW