Conventional lipid bilayer liposomes have similar inner and outer leaflet compositions; asymmetric liposomes have different lipid leaflet compositions. The goal of this work is to place cationic lipids in the inner leaflet to encapsulate negatively charged polynucleotides and to place neutral/anionic lipids on the outer leaflet to decrease nonspecific cellular uptake/toxicity. Inverse emulsion particles have been developed with a single lipid leaflet of cationic and neutral lipids surrounding an aqueous core containing a negatively charged 21-mer DNA oligo. The particles are accelerated through an oil-water interface, entrapping a second neutral lipid to form oligo encapsulated unilamellar liposome nanoparticles. Inverse emulsion particles can be consistently produced to encapsulate an aqueous environment containing negatively charged oligo. The efficiency of encapsulated liposome formation is low and depends on the hydrocarbon used as the oil phase. Dodecane, mineral oil, and squalene were tested, and squalene, a branched hydrocarbon, yielded the highest efficiency.
A localized and effective innate immune response to pathogenic bacterial invasion is central to host survival. Identification of the critical local innate mediators of lung defense against such pathogens is essential for a complete understanding of the mechanism(s) underlying effective host defense. In an acute model of Streptococcus pneumoniae lung infection, deficiency in matrix metalloproteinase (MMP)2 and MMP9 (Mmp2/9−/−) conferred a survival disadvantage relative to wild-type mice treated under the same conditions. S. pneumoniae-infected Mmp2/9−/− mice recruited more polymorphonuclear leukocytes to the lung but had higher bacterial burdens. Mmp2/9−/− mice showed significantly higher levels of IL-17A, IP-10, and RANTES in the lung. Although MMP2-dependent cleavage partially inactivated IL-17A, MMP9 was critical for effective bacterial phagocytosis and reactive oxygen species generation in polymorphonuclear neutrophils. These data demonstrate critical nonredundant and protective roles for MMP2 and MMP9 in the early host immune response against S. pneumoniae infection.
Gas hydrates are an attractive source of energy as natural gas can be produced from these deposits by depressurization or thermal stimulation. Empirical correlations developed in hydrology and petroleum engineering have been used for describing transport properties of sediments containing gas hydrates in hydrate simulators. The goal of this work is to estimate the transport properties of hydrate-bearing sediments from pore-scale modeling. Sediment particles have been packed using a discrete element method and pore radius distribution is calculated using Delaunay triangulation. Hydrate deposition is modeled in a single pore to develop pore-scale laws of hydrate occupancy. Pore radius distributions are recalculated after hydrate deposition. Percolation theory is used to numerically calculate effective transport properties of the medium at different saturations. Pore-scale models showed that the hydrates form at the pore walls if deposited from the flow of methane-saturated water alone. The saturation of hydrate deposited in different size pores was found to be uniform. A Gaussian distribution of particle size of the sediment results in a Rayleigh distribution of pore throat radius. As the variance of the particle size increases, so does the width of the pore size distribution. As the hydrate saturation increases, the permeability of the sediment decreases. This decrease follows Civan's correlation with a ß of 0.75. The relative permeability becomes increasingly dependent on water saturation as the hydrate saturation in the sediment increases. A new correlation for relative permeability is developed by matching the percolation theory estimates. Introduction Gas hydrates are ice-like structures of gas (e.g. methane) and water molecules (Sloan, 1998). They form at high pressure and low temperature conditions. Methane reactes with water to form hydrates according to the following equation: EQUATION where n is the hydration number. Hydrates of hydrocarbon gases occur naturally in large quatities in marine and arctic environments. Hydrate of methane gas contains 164 times the amount of methane in same volume as compared to volume of pure gas at standard conditions. This makes hydrate reservoirs a potential energy source. Hydrates can pose hazard to global climate if the naturally occurring hydrates would dissociate due to global warming. An efficient and safe method of producing natural gas from hydrate reservoirs is necessary to make the production commercial. Different methods and their combinations for the production from hydrates have been proposed: depressurization, thermal stimulation, inhibitor injection, and CO2 injection (Makogon, 1997; Ji et al., 2001; Graue et al., 2006). Laboratory experiments have been conducted to demonstrate the feasibility of these methods of hydrate dissociation. Many numerical simulation efforts at the reservoir scale have been made to estimate the production strategies of hydrate reservoirs (Moridis et. al. 2008, Phirani and Mohanty, 2009, Phirani et. al. 2009). US DOE has conduncted a code comparison study to compare several simulators of hydrates available today (Wilder et.al, 2008).
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