Gas-filled microbubble-mediated delivery of antigen and the induction of immune responses.

The use of well characterized recombinant or purified protein antigens (Ag) for vaccination is of interest for safety reasons and in the case where inactivated pathogens are not available (cancer, allergy). However it requires the addition of adjuvants such as Ag carrier or immune stimulators to potentiate their immunogenicity. In this study, we demonstrated that gas-filled microbubbles (MB) can serve as an efficient Ag delivery system to promote phagocytosis of the model Ag ovalbumin (OVA) without the need of ultrasound application. Once internalized by DC, OVA was processed and presented to both CD4 and CD8 T cells in vitro; such observations were coupled with the capacity of MB to activate DC. In vivo administration of MB-associated OVA in naïve wild-type Balb/c mice resulted in the induction of OVA-specific antibody and T cell responses. Detailed characterization of the generated immune response demonstrated the production of both IgG1 and IgG2a serum antibodies, as well as the secretion of IFN-γ and IL-10 by splenocytes. Interestingly, similar results were obtained with human DC in regards of Ag delivery and cell activation. Therefore, the data presented here settle the proof of principle for the further evaluation of MB-based immunomodulation studies.

The phagocytosis of gas-filled microbubbles by human and murine antigen-presenting cells.

This study was designed to evaluate the potential of gas-filled microbubbles (MB) to be internalized by antigen-presenting cells (APC). Fluorescently labeled MB were prepared, thus permitting to track binding to, and internalization in, APC. Both human and mouse cells, including monocytes and dendritic cells (DC), prove capable to phagocyte MB in vitro. Observation by confocal laser scanning microscopy showed that interaction between MB and target cells resulted in a rapid internalization in cellular compartments and to a lesser extent in the cytoplasm. Capture of MB by APC resulted in phagolysosomal targeting as verified by double staining with anti-lysosome-associated membrane protein-1 monoclonal antibody and decrease of internalization by phagocytosis inhibitors. Fluorescent MB injected subcutaneously (s.c.) in mice were found to be associated with CD11c(+)DC in lymph nodes draining the injection sites 24 h after administration. Altogether, our study demonstrates that MB can successfully target APC both in vitro and in vivo, and thus may serve as a potent Ag delivery system without requirement for ultrasound-based sonoporation. This adds to the potential of applications of MB already extensively used for diagnostic imaging in humans.

Charged AdS black holes and catastrophic holography

We compute the properties of a class of charged black holes in antide Sitter space-time, in diverse dimensions. These black holes are solutions of consistent Einstein-Maxwell truncations of gauged supergravities, which are shown to arise from the inclusion of rotation in the transverse space. We uncover rich thermodynamic phase structures for these systems, which display classic critical phenomena, including structures isomorphic to the van der WaalsMaxwell liquid-gas system. In that case, the phases are controlled by the universal cusp and swallowtail shapes familiar from catastrophe theory. All of the thermodynamics is consistent with field theory interpretations via holography, where the dual field theories can sometimes be found on the world volumes of coincident rotating branes.

Static structure and dynamics of the liquid Li-Na and Li-Mg alloys

We present calculations for the static structure and ordering properties of two lithium-based s-p bonded liquid alloys, Li-Na and Li-Mg. Our theoretical approach is based on the neutral pseudoatom method to derive the interatomic pair potentials, and on the modified-hypernetted-chain theory of liquids to obtain the liquid static structure, leading to a whole combination that is free of adjustable parameters. The study is complemented by performing molecular dynamics simulations which, besides checking the theoretical static structural results, also allow a calculation of some dynamical properties. The obtained results are compared with the available experimental data.

Intramolecular coupling as a mechanism for a liquid-liquid phase transition

We study a model for water with a tunable intramolecular interaction Js, using mean-field theory and off-lattice Monte Carlo simulations. For all Js>~0, the model displays a temperature of maximum density. For a finite intramolecular interaction Js>0, our calculations support the presence of a liquid-liquid phase transition with a possible liquid-liquid critical point for water, likely preempted by inevitable freezing. For J=0, the liquid-liquid critical point disappears at T=0.

Computer simulation study of liquid lithium at 470 and 843 K

Both structural and dynamical properties of 7Li at 470 and 843 K are studied by molecular dynamics simulation and the results are comapred with the available experimental data. Two effective interatomic potentials are used, i.e., a potential derived from the Ashcroft pseudopotential [Phys. Lett. 23, 48 (1966)] and a recently proposed potential deduced from the neutral pseudoatom method [J. Phys.: Condens. Matter 5, 4283 (1993)]. Although the shape of the two potential functions is very different, the majority of the properties calculated from them are very similar. The differences among the results using the two interaction models are carefully discussed.

Static and dynamic structure of liquid metals: Role of the different parts of the interaction potential

The influence of different parts of the interaction potential on the microscopic behavior of simple liquid metals is investigated by molecular dynamics simulation. The role of the soft-core repulsive, short-range attractive, and long-range oscillatory forces on the properties of liquid lithium close to the triple point is analyzed by comparing the results from simulations of identical systems but truncating the potential at different distances. Special attention is paid to dynamic collective properties such as the dynamic structure factors, transverse current correlation functions, and transport coefficients. It is observed that, in general, the effects of the short-range attractive forces are important. On the contrary, the influence of the oscillatory long-range interactions is considerably less, being the most pronounced for the dynamic structure factor at long wavelengths. The results of this work suggest that the influence of the attractive forces becomes less significant when temperature and density increase.

Metastable liquid-liquid phase transition in a single-component system with only one crystal phase and no density anomaly

We investigate the phase behavior of a single-component system in three dimensions with spherically-symmetric, pairwise-additive, soft-core interactions with an attractive well at a long distance, a repulsive soft-core shoulder at an intermediate distance, and a hard-core repulsion at a short distance, similar to potentials used to describe liquid systems such as colloids, protein solutions, or liquid metals. We showed [Nature (London) 409, 692 (2001)] that, even with no evidence of the density anomaly, the phase diagram has two first-order fluid-fluid phase transitions, one ending in a gas¿low-density-liquid (LDL) critical point, and the other in a gas¿high-density-liquid (HDL) critical point, with a LDL-HDL phase transition at low temperatures. Here we use integral equation calculations to explore the three-parameter space of the soft-core potential and perform molecular dynamics simulations in the interesting region of parameters. For the equilibrium phase diagram, we analyze the structure of the crystal phase and find that, within the considered range of densities, the structure is independent of the density. Then, we analyze in detail the fluid metastable phases and, by explicit thermodynamic calculation in the supercooled phase, we show the absence of the density anomaly. We suggest that this absence is related to the presence of only one stable crystal structure.

Dynamic properties of Lennard Jones fluids and liquid metals

The dependence of the dynamic properties of liquid metals and Lennard-Jones fluids on the characteristics of the interaction potentials is analyzed. Molecular-dynamics simulations of liquids in analogous conditions but assuming that their particles interact either through a Lennard-Jones or a liquid-metal potential were carried out. The Lennard-Jones potentials were chosen so that both the effective size of the particles and the depth of the potential well were very close to those of the liquid-metal potentials. In order to investigate the extent to which the dynamic properties of liquids depend on the short-range attractive interactions as well as on the softness of the potential cores, molecular-dynamics simulations of the same systems but assuming purely repulsive interactions with the same potential cores were also performed. The study includes both singleparticle dynamic properties, such as the velocity autocorrelation functions, and collective dynamic properties, such as the intermediate scattering funcfunctions, and collective dynamic properties, such as the intermediate scattering functions, the dynamic structure factors, the longitudinal and transverse current correlations, and the transport coefficients.

Greenhouse Gas and Nitrogen Fertilizer Scenarios for U.S. Agriculture and Global Biofuels, June 2011

This analysis uses the 2011 FAPRI-CARD (Food and Agricultural Policy Research Institute–Center for Agricultural and Rural Development) baseline to evaluate the impact of four alternative scenarios on U.S. and world agricultural markets, as well as on world fertilizer use and world agricultural greenhouse gas emissions. A key assumption in the 2011 baseline is that ethanol support policies disappear in 2012. The baseline also assumes that existing biofuel mandates remain in place and are binding. Two of the scenarios are adverse supply shocks, the first being a 10% increase in the price of nitrogen fertilizer in the United States, and the second, a reversion of cropland into forestland. The third scenario examines how lower energy prices would impact world agriculture. The fourth scenario reintroduces biofuel tax credits and duties. Given that the baseline excludes these policies, the fourth scenario is an attempt to understand the impact of these policies under the market conditions that prevail in early 2011. A key to understanding the results of this fourth scenario is that in the absence of tax credits and duties, the mandate drives biofuel use. Therefore, when the tax credits and duties are reintroduced, the impacts are relatively small. In general, the results show that the entire international commodity market system is remarkably robust with respect to policy changes in one country or in one sector. The policy implication is that domestic policy changes implemented by a large agricultural producer like the United States can have fairly significant impacts on the aggregate world commodity markets. A second point that emerges from the results is that the law of unintended consequences is at work in world agriculture. For example, a U.S. nitrogen tax that might presumably be motivated for environmental benefit results in an increase in world greenhouse gas emissions. A similar situation occurs in the afforestation scenario in which crop production shifts from high-yielding land in the United States to low-yielding land and probably native vegetation in the rest of the world, resulting in an unintended increase in global greenhouse gas emissions.

Finite-size scaling investigation of the liquid-liquid critical point in ST2 water and its stability with respect to crystallization.

The liquid-liquid critical point scenario of water hypothesizes the existence of two metastable liq- uid phases low-density liquid (LDL) and high-density liquid (HDL) deep within the supercooled region. The hypothesis originates from computer simulations of the ST2 water model, but the stabil- ity of the LDL phase with respect to the crystal is still being debated. We simulate supercooled ST2 water at constant pressure, constant temperature, and constant number of molecules N for N ≤ 729 and times up to 1 μs. We observe clear differences between the two liquids, both structural and dynamical. Using several methods, including finite-size scaling, we confirm the presence of a liquid-liquid phase transition ending in a critical point. We find that the LDL is stable with respect to the crystal in 98% of our runs (we perform 372 runs for LDL or LDL-like states), and in 100% of our runs for the two largest system sizes (N = 512 and 729, for which we perform 136 runs for LDL or LDL-like states). In all these runs, tiny crystallites grow and then melt within 1 μs. Only for N ≤ 343 we observe six events (over 236 runs for LDL or LDL-like states) of spontaneous crystal- lization after crystallites reach an estimated critical size of about 70 ± 10 molecules.

Atraso económico y resistencia a la innovación: el caso del gas natural en España

El desarrollo desigual de las economias en el pasado constituye un factor determinante de la distinta capacidad de los paises para aprovechar las mejoras tecnológicas. En algunos casos, 10s menos, el atraso económico puede jugar un papel positivo, al reducir las resistencias que toda innovación genera. En los más, sin embargo, la debilidad del desarrollo anterior constituye un lastre dificil de superar. Suele destacarse, en este sentido, que en las sociedades de menor nivel de desarrollo las disponibilidades de capital para nuevas inversiones acostumbran a ser escasas, y que la demanda, estimulo indispensable, está limitada por los bajos niveles de renta. Pero se olvida a menudo que el resultado de un desarrollo económico lento es siempre una infraestructura muy limitada, que puede significar una dificultad considerable en el momento de plantear una mejora de los procesos de producción.

Second hand tobacco smoke exposure in Switzerland

A passive sampling device called Monitor of NICotine or "MoNIC", was constructed and evaluated by IST laboratory for determining nicotine in Second Hand Tobacco Smoke (SHTS) or Environmental Tobacco Smoke (ETS). Vapour nicotine was passively collected on a potassium bisulfate treated glass fibre filter as collection medium. Analysis of collected nicotine on the treated filter by gas chromatography equipped with Thermoionic-Specific Detector (GC-TSD) after liquid-liquid extraction of 1mL of 5N NaOH : 1 mL of n-heptane saturated with NH3 using quinoline as internal standard. Based on nicotine amount of 0.2 mg/cigarette as the reference, the inhaled Cigarette Equivalents (CE) by non-smokers can be calculated. Using the detected CE on the badge for non-smokers, and comparing with amount of nicotine and cotinine level in saliva of both smokers and exposed non-smokers, we can confirm the use of the CE concept for estimating exposure to ETS. The regional CIPRET (Center of information and prevention of the addiction to smoking) of different cantons (Valais (VS), Vaud (VD), Neuchâtel (NE) and Fribourg (FR)) are going to organize a big campaign on the subject of the passive addiction to smoking. This campaign took place in 2007-2008 and has for objective to inform clearly the Swiss population of the dangerousness of the passive smoke. More than 3'900 MoNIC badges were gracefully distributed to Swiss population to perform a self-monitoring of population exposure level to ETS, expressed in term of CE. Non-stimulated saliva was also collected to determine ETS biomarkers nicotine/cotinine levels of participating volunteers. Results of different levels of CE in occupational and non-occupational situations in relation with ETS were presented in this study. This study, unique in Switzerland, has established a base map on the population's exposure to SHTS. It underscored the fact that all the Swiss people involved in this campaign (N=1241) is exposed to passive smoke, from <0.2 cig/d (10.8%), 1-2 to more than 10 cig/d (89.2%). In the area of high exposure (15-38 cig/d), are the most workers in public restaurant, cafe, bar, disco. By monitoring ETS tracer nicotine and its biomarkers, salivary nicotine and cotinine, it is demonstrated that the MoNIC badge can serve as indicator of CE passive smoking. The MoNIC badge, accompanied with content of salivary nicotine/cotinine can serve as a tool of evaluation of the ETS passive smoking and contributes to supply useful data for future epidemiological studies. It is also demonstrated that the salivary nicotine (without stimulation) is a better biomarker of ETS exposure than cotinine.

First day of an oil spill on the open sea: early mass transfers of hydrocarbons to air and water.

During the first hours after release of petroleum at sea, crude oil hydrocarbons partition rapidly into air and water. However, limited information is available about very early evaporation and dissolution processes. We report on the composition of the oil slick during the first day after a permitted, unrestrained 4.3 m(3) oil release conducted on the North Sea. Rapid mass transfers of volatile and soluble hydrocarbons were observed, with >50% of ≤C17 hydrocarbons disappearing within 25 h from this oil slick of <10 km(2) area and <10 μm thickness. For oil sheen, >50% losses of ≤C16 hydrocarbons were observed after 1 h. We developed a mass transfer model to describe the evolution of oil slick chemical composition and water column hydrocarbon concentrations. The model was parametrized based on environmental conditions and hydrocarbon partitioning properties estimated from comprehensive two-dimensional gas chromatography (GC×GC) retention data. The model correctly predicted the observed fractionation of petroleum hydrocarbons in the oil slick resulting from evaporation and dissolution. This is the first report on the broad-spectrum compositional changes in oil during the first day of a spill at the sea surface. Expected outcomes under other environmental conditions are discussed, as well as comparisons to other models.