Ag85A DNA Vaccine Delivery by Nanoparticles: Influence of the Formulation Characteristics on Immune Responses.

The influence of DNA vaccine formulations on immune responses in combination with adjuvants was investigated with the aim to increase cell-mediated immunity against plasmid DNA (pDNA) encoding Mycobacterium tuberculosis antigen 85A. Different ratios of pDNA with cationic trimethyl chitosan (TMC) nanoparticles were characterized for their morphology and physicochemical characteristics (size, zeta potential, loading efficiency and pDNA release profile) applied in vitro for cellular uptake studies and in vivo, to determine the dose-dependent effects of pDNA on immune responses. A selected pDNA/TMC nanoparticle formulation was optimized by the incorporation of muramyl dipeptide (MDP) as an immunostimulatory agent. Cellular uptake investigations in vitro showed saturation to a maximum level upon the increase in the pDNA/TMC nanoparticle ratio, correlating with increasing Th1-related antibody responses up to a definite pDNA dose applied. Moreover, TMC nanoparticles induced clear polarization towards a Th1 response, indicated by IgG2c/IgG1 ratios above unity and enhanced numbers of antigen-specific IFN-γ producing T-cells in the spleen. Remarkably, the incorporation of MDP in TMC nanoparticles provoked a significant additional increase in T-cell-mediated responses induced by pDNA. In conclusion, pDNA-loaded TMC nanoparticles are capable of provoking strong Th1-type cellular and humoral immune responses, with the potential to be further optimized by the incorporation of MDP

Interactions between the Somali Current eddies during the summer monsoon: insights from a numerical study

International audienceThree hindcast simulations of the global ocean circulation differing by resolution (1/4 or 1/12°) or parametrization or atmospheric forcing are used to describe the interactions between the large anticyclonic eddies generated by the Somali Current system during the Southwest Monsoon. The present investigation of the Somalian coherent eddy structures allows us to identify the origin and the subsequent development of the cyclones flanked upon the Great Whirl (GW) previously identified by Beal and Dono-hue (2013) in satellite observations and to establish that similar cyclones are also flanked upon the Southern Gyre (SG). These cyclones are identified as potential actors in mixing water masses within the large eddies and offshore the coast of Somalia. All three simulations bring to light that during the period when the Southwest Monsoon is well established, the SG moves northward along the Somali coast and encounters the GW. The interaction between the SG and the GW is a collision without merging, in a way that has not been described in observations up to now. During the collision the GW is pushed to the east of Socotra Island, sheds several smaller patches of anticyclonic vorticity, and often reforms into the Socotra Eddy, thus proposing a formation mechanism for that eddy. During this process the GW gives up its place to the SG. This process is robust throughout the three simulations

A componential approach to individual differences in hypnotizability

Although responsiveness to hypnotic suggestions (hypnotizability) typically is conceptualized and studied as a singular homogeneous capability, numerous lines of evidence suggest instead that it is a hierarchically structured cognitive capacity comprising a core superordinate ability and ancillary subordinate component abilities. After reviewing current approaches to the measurement of hypnotizability and componential approaches to other cognitive capabilities, we highlight outstanding questions in the field and argue for a componential approach to the study of hypnotizability. Such an approach assumes that hypnotizability is not a unitary construct but is rooted in multiple subabilities that interact to give rise to individual differences that are expressed within specific contexts. We revisit previous componential work on hypnotizability and propose a series of steps by which a componential model can be more rigorously interrogated and integrated with contemporary advances in our understanding of human cognition

Optimal adjustment of the atmospheric forcing parameters of ocean models using sea surface temperature data assimilation

In ocean general circulation models, near-surface atmospheric variables used to specify the atmospheric boundary condition remain one of the main sources of error. The objective of this research is to constrain the surface forcing function of an ocean model by sea surface temperature (SST) data assimilation. For that purpose, a set of corrections for ERAinterim (hereafter ERAi) reanalysis data is estimated for the period of 1989–2007, using a sequential assimilation method, with ensemble experiments to evaluate the impact of uncertain atmospheric forcing on the ocean state. The control vector of the assimilation method is extended to atmospheric variables to obtain monthly mean parameter corrections by assimilating monthly SST and sea surface salinity (SSS) climatological data in a low resolution global configuration of the NEMO model. In this context, the careful determination of the prior probability distribution of the parameters is an important matter. This paper demonstrates the importance of isolating the impact of forcing errors in the model to perform relevant ensemble experiments. <br><br> The results obtained for every month of the period between 1989 and 2007 show that the estimated parameters produce the same kind of impact on the SST as the analysis itself. The objective is then to evaluate the long-term time series of the forcing parameters focusing on trends and mean error corrections of air–sea fluxes. Our corrections tend to equilibrate the net heat-flux balance at the global scale (highly positive in ERAi database), and to remove the potentially unrealistic negative trend (leading to ocean cooling) in the ERAi net heat flux over the whole time period. More specifically in the intertropical band, we reduce the warm bias of ERAi data by mostly modifying the latent heat flux by wind speed intensification. Consistently, when used to force the model, the corrected parameters lead to a better agreement between the mean SST produced by the model and mean SST observations over the period of 1989–2007 in the intertropical band

The impact of self-reported hearing difficulties on memory collaboration in older adults

Cognitive scientists and philosophers recently have highlighted the value of thinking about people at risk of or living with dementia as intertwined parts of broader cognitive systems that involve their spouse, family, friends, or carers. By this view, we rely on people and things around us to “scaffold” mental processes such as memory. In the current study, we identified 39 long-married, older adult couples who are part of the Australian Imaging Biomarkers and Lifestyle (AIBL) Study of Ageing; all were cognitively healthy but half were subjective memory complainers. During two visits to their homes 1 week apart, we assessed husbands’ and wives’ cognitive performance across a range of everyday memory tasks working alone (Week 1) versus together (Week 2), including a Friends Task where they provided first and last names of their friends and acquaintances. As reported elsewhere, elderly couples recalled many more friends’ names working together compared to alone. Couples who remembered successfully together used well-developed, rich, sensitive, and dynamic communication strategies to boost each other’s recall. However, if one or both spouses self-reported mild-to-moderate or severe hearing difficulties (56% of husbands, 31% of wives), couples received less benefit from collaboration. Our findings imply that hearing loss may disrupt collaborative support structures that couples (and other intimate communicative partners) hone over decades together. We discuss the possibility that, cut off from the social world that scaffolds them, hearing loss may place older adults at greater risk of cognitive decline and dementia

Transfer of particulate matter from the Northwestern Mediterranean continental margin: Variability and controlling factors

International audienceLong-term observations of monthly downward particle fluxes and hourly currents and temperaturewere initiated in 1993 in two canyons of the continental margin of the Gulf of Lion. The goals of thissurvey were to estimate its contribution to the CO 2 global budget and to understand the role offorcing factors in the control of present-day particle exchange across this margin. A previousstatistical analysis of the long-term time series suggested that variability in the transfer of particulatematter to the deep ocean could be the result of the effect of the meandering of the Northern Currentand by dense water formation in winter rather than variations in the sources of matter. Numericalsimulations have been carried out to consider these hypotheses. A model is used to examine theimpact of local atmospheric forcing (wind stress, heat fluxes, precipitation–evaporation budget) onthe variability of the oceanic circulation and of mass fluxes within the canyons from December toApril, for five consecutive years between 1996 and 2001. Results show an east-west gradient of massexport on the shelf and a positive correlation between anomalies of dense water formation rates andinterannual variability of particle fluxes. However, in the eastern part of the Gulf, the simulated massexport from the shelf is not significant, even during a winter of strong convection, when the measuredparticle fluxes are at maxima. Moreover, although the model suggests that the dense water formationcould be the major hydrodynamic forcing factor, this process is not sufficient to completely explainthe space and time variations of observed particle fluxes, especially at depth

Simulations of a Line W-based observing system for the Atlantic meridional overturning circulation

In a series of observing system simulations, we test whether the Atlantic meridional overturning circulation (AMOC) can be observed based on the existing Line W deep western boundary array. We simulate a Line W array, which is extended to the surface and to the east to cover the basin to the Bermuda Rise. In the analyzed ocean circulation model ORCA025, such an extended Line W array captures the main characteristics of the western boundary current. Potential trans-basin observing systems for the AMOC are tested by combining the extended Line W array with a mid-ocean transport estimate obtained from thermal wind "measurements" and Ekman transport to the total AMOC (similarly to Hirschi et al., Geophys Res Lett 30(7):1413, 2003). First, we close Line W zonally supplementing the western boundary array with several "moorings" in the basin (Line W-32A degrees N). Second, we supplement the western boundary array with a combination of observations at Bermuda and the eastern part of the RAPID array at 26A degrees N (Line W-B-RAPID). Both, a small number of density profiles across the basin and also only sampling the eastern and western boundary, capture the variability of the AMOC at Line W-32A degrees N and Line W-B-RAPID. In the analyzed model, the AMOC variability at both Line W-32A degrees N and Line W-B-RAPID is dominated by the western boundary current variability. Away from the western boundary, the mid-ocean transport (east of Bermuda) shows no significant relation between the two Line W-based sections and 26A degrees N. Hence, a Line W-based AMOC estimate could yield an estimate of the meridional transport that is independent of the 26A degrees N RAPID estimate. The model-based observing system simulations presented here provide support for the use of Line W as a cornerstone for a trans-basin AMOC observing system