The ability of low-frequency ultrasound (LFUS) to release encapsulated drugs from sterically stabilized liposomes in a controlled manner was demonstrated. Three liposomal formulations having identical lipid bilayer compositions and a similar size ( approximately 100 nm) but differing in their encapsulated drugs and methods of drug loading have been tested. Two of the drugs, doxorubicin and methylpredinisolone hemisuccinate, were remote loaded by transmembrane gradients (ammonium sulfate and calcium acetate, respectively). The third drug, cisplatin, was loaded passively into the liposomes. For all three formulations, a short exposure to LFUS (<3 min) released nearly 80% of the drug. The magnitude of drug release was a function of LFUS amplitude and actual exposure time, irrespective of whether irradiation was pulsed or continuous. Furthermore, no change in liposome size distribution or in the chemical properties of the lipids or of the released drugs occurred due to exposure to LFUS. Based on our results, we propose that the mechanism of release is a transient introduction of porelike defects in the liposome membrane, which occurs only during exposure to LFUS, after which the membrane reseals. This explains the observed uptake of the membrane-impermeable fluorophore pyranine from the extraliposomal medium during exposure to LFUS. The implications of these findings for clinical applications of controlled drug release from liposomes are discussed. 相似文献
monotone span programs computing explicit functions. The best previous lower bound was by Beimel, Gál, Paterson [7]; our proof exploits a general combinatorial lower bound criterion from that paper. Our lower
bounds are based on an analysis of Paley-type bipartite graphs via Weil's character sum estimates. We prove an lower bound for the size of monotone span programs for the clique problem. Our results give the first superpolynomial lower
bounds for linear secret sharing schemes.
We demonstrate the surprising power of monotone span programs by exhibiting a function computable in this model in linear
size while requiring superpolynomial size monotone circuits and exponential size monotone formulae. We also show that the
perfect matching function can be computed by polynomial size (non-monotone) span programs over arbitrary fields.
Received: August 1, 1996 相似文献
n and 0 < δ < 1, we construct graphs on n nodes such that every two sets of size share an edge, having essentially optimal maximum degree . Using known and new reductions from these graphs, we derive new explicit constructions of:
1. A k round sorting algorithm using comparisons.
2. A k round selection algorithm using comparisons.
3. A depth 2 superconcentrator of size .
4. A depth k wide-sense nonblocking generalized connector of size .
All of these results improve on previous constructions by factors of , and are optimal to within factors of . These results are based on an improvement to the extractor construction of Nisan & Zuckerman: our algorithm extracts an
asymptotically optimal number of random bits from a defective random source using a small additional number of truly random
bits.
Received: June 13, 1995/Revised: Revised October 23, 1998 相似文献
The quality of solvents of polymers is often described in terms of the Flory χ parameter typically assumed to depend only on the temperature, T. In certain polymer‐solvent systems fitting the experimental data enforces the replacement of (χT) by a concentration‐dependent χeff. In turn, this modifies the swelling and collapse behavior. These effects are studied, in the framework of a mean‐field theory, for isolated coils and for planar brushes. The ϕ dependence of χeff gives rise to three main consequences: (i) shift in the cross‐over between Gaussian and self‐avoidance regimes; (ii) a possibility of first‐order collapse transition for isolated flexible coils; (iii) the possibility of a first‐order phase transition leading to a vertical phase separation within the brush. The discussion relates these effects directly to thermodynamic measurements and does not involve a specific microscopic model. The implementation for the case of poly(N‐isopropylamide) (PNIPAM) brushes is discussed.
ϕ vs. z plots, for brushes with N = 300, σ/a2 = 18 (σ/R = 0.019) characterized by different χeff. 相似文献
The selection of either an oxidising or inert ambient during high temperature annealing is shown to affect dopant activation and electron–hole recombination in boron implanted silicon samples. Samples implanted with B at fluence between 3 × 1014 cm–2 to 3 × 1015 cm–2 are shown to have lower dopant activation after oxidation at 1000 °C compared to an equivalent anneal in an inert ambient. In addition, emitter recombination is shown to be up to 15 times higher after oxidation compared with an inert anneal for samples with equivalent passivation from deposited Al2O3 films. The observed increase in recombination for oxidised samples is attributed to the enhanced formation of boron‐interstitial defect clusters and dislocation loops under oxidising conditions. It is also shown that an inert anneal for 10 minutes at 1000 °C prior to oxidation has no significant impact on sheet resistance or recombination compared with a standard oxidation process.
Size-reduction systems have been extensively used in industry for many years. Nevertheless, reliable engineering tools to be used to predict the comminution of particles are scarce. Computational fluid dynamics(CFD)–discrete element model(DEM) numerical simulation may be used to predict such a complex phenomenon and therefore establish a proper design and optimization model for comminution systems.They may also be used to predict attrition in systems where particle attrition is significant. Therefore,empirical comminution functions(which are applicable for any attrition/comminution process), such as:strength distribution, selection, equivalence, breakage, and fatigue, have been integrated into the threedimensional CFD–DEM simulation tool. The main drawback of such a design tool is the long computational time required owing to the large number of particles and the minute time-step required to maintain a steady solution while simulating the flow of particulate materials with very fine particles.The present study developed several methods to accelerate CFD–DEM simulations: reducing the number of operations carried out at the single-particle level, constructing a DEM grid detached from the CFD grid enabling a no binary search, generating a sub-grid within the DEM grid to enable a no binary search for fine particles, and increasing the computational time-step and eliminating the finest particles in the simulation while still tracking their contribution to the process.The total speedup of the simulation process without the elimination of the finest particles was a factor of about 17. The elimination of the finest particles gave additional speedup of a factor of at least 18.Therefore, the simulation of a grinding process can run at least 300 times faster than the conventional method in which a standard no binary search is employed and the smallest particles are tracked. 相似文献
Remarkably, uniform virus-like particles self-assemble in a process that appears to follow a rapid kinetic mechanism. The mechanisms by which spherical viruses assemble from hundreds of capsid proteins around nucleic acid, however, are yet unresolved. Using time-resolved small-angle X-ray scattering (TR-SAXS), we have been able to directly visualize SV40 VP1 pentamers encapsidating short RNA molecules (500mers). This assembly process yields T = 1 icosahedral particles comprised of 12 pentamers and one RNA molecule. The reaction is nearly one-third complete within 35 ms, following a two-state kinetic process with no detectable intermediates. Theoretical analysis of kinetics, using a master equation, shows that the assembly process nucleates at the RNA and continues by a cascade of elongation reactions in which one VP1 pentamer is added at a time, with a rate of approximately 10(9) M(-1) s(-1). The reaction is highly robust and faster than the predicted diffusion limit. The emerging molecular mechanism, which appears to be general to viruses that assemble around nucleic acids, implicates long-ranged electrostatic interactions. The model proposes that the growing nucleo-protein complex acts as an electrostatic antenna that attracts other capsid subunits for the encapsidation process. 相似文献