Search

With the long-term goal of developing a gene-based treatment for osteoarthritis (OA), we performed studies to evaluate the equine joint as a model for adeno-associated virus (AAV)-mediated gene transfer to large, weight-bearing human joints. A self-complementary AAV2 vector containing the coding regions for human interleukin-1-receptor antagonist (hIL-1Ra) or green fluorescent protein was packaged in AAV capsid serotypes 1, 2, 5, 8 and 9. Following infection of human and equine synovial fibroblasts in culture, we found that both were only receptive to transduction with AAV1, 2 and 5. For these serotypes, however, transgene expression from the equine cells was consistently at least 10-fold higher. Analyses of AAV surface receptor molecules and intracellular trafficking of vector genomes implicate enhanced viral uptake by the equine cells. Following delivery of 1 × 1011 vector genomes of serotypes 2, 5 and 8 into the forelimb joints of the horse, all three enabled hIL-1Ra expression at biologically relevant levels and effectively transduced the same cell types, primarily synovial fibroblasts and, to a lesser degree, chondrocytes in articular cartilage. These results provide optimism that AAV vectors can be effectively adapted for gene delivery to large human joints affected by OA. [ABSTRACT FROM AUTHOR]

We investigated the role of prepulse laser wavelength on extreme-ultraviolet (EUV) emission and ionic debris generation. A 6 ns Nd:YAG laser operating at 266 nm was used to generate a pre-plasma that was then reheated by a 35 ns CO laser pumping pulse at 10.6 μm. At an ideal delay time, improvement in EUV conversion efficiency (CE) of up to 30 % was seen compared to the CE from the pumping pulse alone. It was also shown that the most probable Sn ion kinetic energies were reduced significantly with the use of a prepulse, however, ion fluence increased. These results were compared to those obtained using a 1064 nm prepulse. [ABSTRACT FROM AUTHOR]

Therapeutic aerosol bioengineering (TAB) of Mycobacterium tuberculosis ( MTb) therapies using inhalable microparticles offers a unique opportunity to target drugs to the site of infection in the alveolar macrophages, thereby increasing dosing in the lungs and limiting systemic exposure to often toxic drugs. Previous work by us used sophisticated, high content analysis to design the optimal poly(lactide-co-glycolic) acid (PLGA) microparticle for delivery of drugs to alveolar macrophages. Herein, we applied this technology to three different anti- MTb drugs. These formulations were then tested for encapsulation efficiency, drug-release, in vitro killing against MTb and aerosol performance. Methods for encapsulating each of the drugs in the PLGA microparticles were successfully developed and found to be capable of controlling the release of the drug for up to 4 days. The efficacy of each of the encapsulated anti- MTb drugs was maintained and in some cases enhanced post-encapsulation. A method of processing these drug-loaded microparticles for inhalation using standard dry powder inhaler devices was successfully developed that enabled a very high respirable dose of the drug to be delivered from a simple dry powder inhaler device. Overall, TAB offers unique opportunities to more effectively treat MTb with many potential clinical and economic benefits resulting. [ABSTRACT FROM AUTHOR]

Field experiments between 1996 and 2000 compared the efficacy of fungicide programmes applied in accordance with the NegFry and Met Éireann (MÉ) decision support systems (DSS) for the control of late blight with 7- and 10-day routine fungicide programmes. The MÉ DSS reduced fungicide use by 68% and 54% respectively while NegFry reduced fungicide use by 49% and 27% compared with the 7- and 10-day programmes. The NegFry DSS was similar to the 10-day routine programme in terms of late blight control, quality and marketable yield. A similar result was found when the NegFry DSS was compared with a 7-day routine mancozeb programme (included for two seasons only). Within the NegFry DSS the use of fluazinam resulted in improved yield, foliage blight and tuber blight control compared with mancozeb, but this benefit was significant for tuber blight only. The MÉ DSS resulted in inferior disease control, yield and quality. [ABSTRACT FROM AUTHOR]

A new semi-empirical potential for Fe based on the quantum chemistry concept of bond order has been developed. The potential consists of two parts: the repulsive short-range exponential potential, and the attractive potential, also of the exponential form, with a bond-order prefactor. The latter depends on angles between the Fe-Fe bonds, and uses the environmental parameter similar to that of the Tersoff bond-order potential for tetrahedrally bonded semiconductors. The bond order function (depending on the above environmental parameter), however, is of a more general form than that of the Tersoff potential. The new potential was calibrated using the traditional fitting to the Universal Scaling and the equilibrium volume and cohesive energy of BCC Fe. The introduced 'punishment functions' also directed the multi-variate minimization process towards minimizing the deviations between the calculated and experimental values of the elastic moduli C′ and C44, the energies of FCC and HCP Fe modifications, and the (111) free surface energy. With the total of 15 fitted parameters, the potential reproduces with only minor deviations the elastic moduli, the volume–pressure equation of states in BCC phase, the energies in FCC and HCP modifications, the BCC-HCP phase transformation under pressure, and the energy of the (111) free surface. Other tests of the new potential are being currently performed. The potential will be used in atomistic simulations of lattice stability, and deformation and chemisorption processes in Fe. [ABSTRACT FROM AUTHOR]

The free energy of formation of magnesium sulfate and its solubility in magnesia have been determined. The salient feature of the results is that trace amounts of calcium impurity in magnesia noticeably lower the dissociation temperature and pressure of magnesium sulfate. A high-purity magnesia, which was prepared by oxidation of a high-purity magnesium, was used to determine the equilibrium constant for the formation of MgSO. The sulfate solubil-ity In magnesia saturated with MgSO was found to be higher than that in lime saturated with CaSO. At 1100°C, CaSO and CaS form in calcined dolomite at SO partial pressures higher than those in pure CaO. From these findings it is estimated that at MgO saturation the ac-tivity coefficient relative to CaO is about 0.8. [ABSTRACT FROM AUTHOR]

In the present work the solid solubilities of CaS and CaSQ, in burnt lime were investigated by equilibrating lime with CO-CO-SO mixtures at temperatures from 950 to 1300°C. Also, the equilibrium constants for the formation of CaS and CaSO were determined. At high oxy-gen activities, corresponding to a CO/CO ratio >100 in the gas, the sulfur dissolves in lime primarily as sulfate ions. At lower oxygen activities (CO/CO <30), the sulfur goes into so-lution in lime essentially as sulfide ions. Over the temperature range investigated the limit-ing sulfide solubility is within 0.01 to 0.03 pct S, whereas the sulfate solubility is within 0.03 to 0.1 pct S, increasing with increasing temperature. [ABSTRACT FROM AUTHOR]