In Vivo Targeting of Antigens to Maturing Dendritic Cells via the DEC-205 Receptor Improves T Cell Vaccination

The prevention and treatment of prevalent infectious diseases and tumors should benefit from improvements in the induction of antigen-specific T cell immunity. To assess the potential of antigen targeting to dendritic cells to improve immunity, we incorporated ovalbumin protein into a monoclonal antibody to the DEC-205 receptor, an endocytic receptor that is abundant on these cells in lymphoid tissues. Simultaneously, we injected agonistic α-CD40 antibody to mature the dendritic cells. We found that a single low dose of antibody-conjugated ovalbumin initiated immunity from the naive CD4+ and CD8+ T cell repertoire. Unexpectedly, the αDEC-205 antigen conjugates, given s.c., targeted to dendritic cells systemically and for long periods, and ovalbumin peptide was presented on MHC class I for 2 weeks. This was associated with stronger CD8+ T cell-mediated immunity relative to other forms of antigen delivery, even when the latter was given at a thousand times higher doses. In parallel, the mice showed enhanced resistance to an established rapidly growing tumor and to viral infection at a mucosal site. By better harnessing the immunizing functions of maturing dendritic cells, antibody-mediated antigen targeting via the DEC-205 receptor increases the efficiency of vaccination for T cell immunity, including systemic and mucosal resistance in disease models

Fast and Selective Separation of Carbon Dioxide from Dilute Streams by Pressure Swing Adsorption using Solid Ionic Liquids

The need to create a new approach to carbon capture processes that are economically viable has led to the design and synthesis of sorbents that selectively capture carbon dioxide by physisorption. Solid Ionic Liquids (SoILs) were targeted because of their tunable properties and solid form under operational conditions. Molecular modelling was used to identify candidate SoILs and a number of materials based on the low cost, environmentally friendly acetate anion were selected. The materials showed excellent selectivity for carbon dioxide over nitrogen and oxygen and moderate sorption capacity. However, the rate of capture was extremely fast, in the order of a few seconds for a complete adsorb-desorb cycle, under pressure swing conditions from 1 to 10 bar. This showed the importance of rate of sorption cycling over capacity and demonstrates that smaller inventories of sorbents and smaller process equipment are required to capture low concentration CO2 streams. Concentrated CO2 was isolated by releasing the pressure back to atmospheric. The low volatility and thermal stability of SoILs mean that both plant costs and materials costs can be reduced and plant size considerably reduced

Observation of a Triangular to Square Flux Lattice Phase Transition in YBCO

We have used the technique of small-angle neutron scattering to observe magnetic flux lines directly in an YBCO single crystal at fields higher than previously reported. For field directions close to perpendicular to the CuO2 planes, we find that the flux lattice structure changes smoothly from a distorted triangular co-ordination to nearly perfectly square as the magnetic induction approaches 11 T. The orientation of the square flux lattice is as expected from recent d-wave theories, but is 45 deg from that recently observed in LSCO

Boundary effects of expectation in human pain perception

Funder: RCUK | Medical Research Council (MRC); doi: https://doi.org/10.13039/501100000265Funder: FONDECYT, 1161378Abstract: Perception of sensory stimulation is influenced by numerous psychological variables. One example is placebo analgesia, where expecting low pain causes a painful stimulus to feel less painful. Yet, because pain evolved to signal threats to survival, it should be maladaptive for highly-erroneous expectations to yield unrealistic pain experiences. Therefore, we hypothesised that a cue followed by a highly discrepant stimulus intensity, which generates a large prediction error, will have a weaker influence on the perception of that stimulus. To test this hypothesis we collected two independent pain-cueing datasets. The second dataset and the analysis plan were preregistered (https://osf.io/5r6z7/). Regression modelling revealed that reported pain intensities were best explained by a quartic polynomial model of the prediction error. The results indicated that the influence of cues on perceived pain decreased when stimulus intensity was very different from expectations, suggesting that prediction error size has an immediate functional role in pain perception

Is there a vortex-glass transition in high-temperature superconductors?

We show that DC voltage versus current measurements of a YBCO micro-bridge in a magnetic field can be collapsed onto scaling functions proposed by Fisher, Fisher, and Huse, as is widely reported in the literature. We find, however, that good data collapse is achieved for a wide range of critical exponents and temperatures. These results strongly suggest that agreement with scaling alone does not prove the existence of a phase transition. We propose a criterion to determine if the data collapse is valid, and thus if a phase transition occurs. To our knowledge, none of the data reported in the literature meet our criterion.Comment: 4 pages, 4 figure

Muons as Local Probes of Three-body Correlations in the Mixed State of Type-II Superconductors

The vortex glass state formed by magnetic flux lines in a type-II superconductor is shown to possess non-trivial three-body correlations. While such correlations are usually difficult to measure in glassy systems, the magnetic fields associated with the flux vortices allow us to probe these via muon-spin rotation measurements of the local field distribution. We show via numerical simulations and analytic calculations that these observations provide detailed microscopic insight into the local order of the vortex glass and more generally validate a theoretical framework for correlations in glassy systems.Comment: 4+ pages, high-quality figures available on reques

Kinetic Theory of Flux Line Hydrodynamics:LIQUID Phase with Disorder

We study the Langevin dynamics of flux lines of high--T$_c$ superconductors in the presence of random quenched pinning. The hydrodynamic theory for the densities is derived by starting with the microscopic model for the flux-line liquid. The dynamic functional is expressed as an expansion in the dynamic order parameter and the corresponding response field. We treat the model within the Gaussian approximation and calculate the dynamic structure function in the presence of pinning disorder. The disorder leads to an additive static peak proportional to the disorder strength. On length scales larger than the line static transverse wandering length and at long times, we recover the hydrodynamic results of simple frictional diffusion, with interactions additively renormalizing the relaxational rate. On shorter length and time scales line internal degrees of freedom significantly modify the dynamics by generating wavevector-dependent corrections to the density relaxation rate.Comment: 61 pages and 6 figures available upon request, plain TEX using Harvard macro

Inter-observer agreement of canine and feline paroxysmal event semiology and classification by veterinary neurology specialists and non-specialists

Background: Advances in mobile technology mean vets are now commonly presented with videos of paroxysmal events by clients, but the consistency of the interpretation of these videos has not been investigated. The objective of this study was to investigate the level of agreement between vets (both neurology specialists and non-specialists) on the description and classification of videos depicting paroxysmal events, without knowing any results of diagnostic workup. An online questionnaire study was conducted, where participants watched 100 videos of dogs and cats exhibiting paroxysmal events and answered questions regarding: epileptic seizure presence (yes/ no), seizure type, consciousness status, and the presence of motor, autonomic and neurobehavioural signs. Agreement statistics (percentage agreement and kappa) calculated for each variable, with prevalence indices calculated to aid their interpretation. Results: Only a fair level of agreement (kappa = 0.40) was found for epileptic seizure presence. Overall agreement of seizure type was moderate (kappa = 0.44), with primary generalised seizures showing the highest level of agreement (kappa = 0.60), and focal the lowest (kappa = 0.31). Fair agreement was found for consciousness status and the presence of autonomic signs (kappa = 0.21-0.40), but poor agreement for neurobehavioral signs (kappa = 0.16). Agreement for motor signs ranged from poor (kappa = <= 0.20) to moderate (kappa = 0.41-0.60). Differences between specialists and non-specialists were identified. Conclusions: The relatively low levels of agreement described here highlight the need for further discussions between neurology experts regarding classifying and describing epileptic seizures, and additional training of non-specialists to facilitate accurate diagnosis. There is a need for diagnostic tools (e.g. electroencephalogram) able to differentiate between epileptic and non-epileptic paroxysms