Study of the influence of the pH media dissolution, degree of polymerization, and degree of swelling of the polymers on the mechanism of release of diltiazem from matrices based on mixtures of chitosan/alginate

The dissolution profiles of formulations based on mixtures of chitosan/alginate depend on the pH. It is possible to distinguish two processes: (a) a fast kinetic drug release up to 180 min, where the pH value changes from 1.17 to 2.21 and the drug released is controlled by the degree of polymerization and the quantity of chitosan in the formulation; (b) a low kinetic drug release between 210 and 480 min, where the pH value changes from 5.52 to 8.72 and the drug release from the matrix is controlled by the interpolymeric complex. In all formulations the order of release, according to Peppas's model in the range of fast kinetic drug release, was between 0.5 and 1.0. The mechanism of release was non-fickian diffusion, which corresponds to a coupling mechanism of diffusion and relaxation of the polymer.     

Tight binding of the antitumor drug ditercalinium to quadruplex DNA

The structural selectivity of the DNA-binding antitumor drug ditercalinium was investigated by competition dialysis with a series of nineteen different DNA substrates. The 7H-pyridocarbazole dimer was found to bind to double-stranded DNA with a preference for GC-rich species but can in addition form stable complexes with triplex and quadruplex structures. The preferential interaction of the drug with four-stranded DNA structures was independently confirmed by electrospray mass spectrometry and a detailed analysis of the binding reaction was performed by surface plasmon resonance (SPR) spectroscopy. The BIAcore SPR study showed that the kinetic parameters for the interaction of ditercalinium with the human telomeric quadruplex sequence are comparable to those measured with a duplex sequence. Slow association and dissociation were observed with both the quadruplex and duplex structures. The newly discovered preferential binding of ditercalinium to the antiparallel quadruplex sequence d(AG(3)[T(2)AG(3)](3)) provides new perspectives for the design of drugs that can bind to human telomeres.     

VLSI placement and area optimization using a genetic algorithm tobreed normalized postfix expressions

We present a genetic algorithm (GA) that uses a slicing tree construction process for the placement and area optimization of soft modules in very large scale integration floorplan design. We have overcome the serious representational problems usually associated with encoding slicing floorplans into GAs and have obtained excellent (often optimal) results for module sets with up to 100 rectangles. The slicing tree construction process used by our GA to generate the floorplans has a runtime scaling of O(n lg n). This compares very favorably with other recent approaches based on nonslicing floorplans that require much longer runtimes. We demonstrate that our GA outperforms a simulated annealing implementation with the same representation and mutation operators as the GA     

Evaluation of the effect of probiotic cultures added to commercial yogurt over a known population of Listeria monocytogenes and Escherichia coli O157:H7

The effect of probiotic cultures over Listeria monocytogenes and Escherichia coli O157:H7 during yogurt storage was evaluated. Two different yogurt brands, one with additional probiotic cultures (Lactobacillus casei and L. acidophilus) were inoculated with known populations (106 UFC/g) of either L. monocytogenes or E. coli O157:H7 in three different times and stored for 32 days at 5 degrees C. Every four days the count of lactic bacteria, the added pathogens and pH was evaluated, according to the methodology described in the Bacteriological Analytical Manual. The pH and lactic bacteria population were constant during the testing period. Yogurt with additional probiotic cultures reduced the population of L. monocytogenes in 8 days, the population of E. coli O157:H7 in 16; yogurt with no additional probiotics took 20 days to reduce L. monocytogenes to non-detectable levels and even after 28 days of storage, E. coli O157:H7 was cultured. In this work, the beneficial effects of additional probiotic cultures in yogurt is confirmed again.     

Heavy metal bioaccumulation and macroinvertebrate community changes in a Mediterranean stream affected by acid mine drainage and an accidental spill (Guadiamar River, SW Spain)

In the 1998 Aznalcóllar mining accident, 5 million cubic meters of toxic waste were spilled into the Guadiamar River (SW Spain). This paper describes the likely effects of metal pollution on the macroinvertebrate community in the first 15 km of the river adjacent to the mine, 2 years after the spill. The contents of Zn, Cu, Pb, As, Cd, Tl, and Sb in water, sediment, and in the caddisfly Hydropsyche were analysed, together with some physico-chemical parameters. From the results of physico-chemical and community parameters, the studied area was divided into three sections: the first section contained upstream control stations, not affected by current mining activities, and with a diverse macroinvertebrate community structure (mean number of families = 19); the second section, close to the mine, was severely polluted, with more than 50 mg l(-1) of Zn or 1.6 mg l(-1) of Cu in water, a pH of nearly 4, and a very diminished macroinvertebrate community (three families); in the last section, 6-15 km downstream from the mine, the water quality improved, metal concentrations decreased, pH reached neutrality and the macroinvertebrate community comprised eight families. We also determined metal concentrations in the larvae of Hydropsyche and found increases of 3- to 35-fold (for Cu and Cd, respectively) compared to control sites. As far as we are aware, these values are the highest concentrations so far detected in this caddisfly anywhere in the world. Different patterns of metal and pH tolerance were identified in macroinvertebrates. Most of the species were intolerant to present pollution levels and were only present in control sites. Others were tolerant to metal pollution but not to low pH and were present in the main river downstream of the mine, while a very few species managed to live in the most polluted section, with very low pH and high metal concentrations.     

Initial in-orbit results from a low-cost atmospheric ozone monitor operating on board the FASat-Bravo microsatellite

In 1994, a collaborative programme was set up between the University of Surrey and the Chilean Air Force to design and build a low-cost 50 kg microsatellite with instrumentation capable of monitoring the distribution and concentration of stratospheric ozone, particularly over Chilean territory. This resulted in the joint design and development of the ozone-layer monitoring experiment (OLME), which was flown on board the resultant FASat-Bravo microsatellite, launched in July 1998 into an 820 km altitude Sun-synchronous orbit. The nadir-pointing OLME measures the solar ultraviolet light backscattered from the atmosphere in four spectral bands. From these raw radiometric data, total column ozone concentrations can be deduced. Since the launch, a series of high-spatial-resolution measurements have been made over Chilean scientific stations, while continuous low-spatial-resolution measurements have been used to provide global coverage. To date, the University of Surrey has concentrated on these global measurements, and has used a simplified ozone retrieval algorithm to check the results qualitatively against ozone maps produced by NASA's Earth Probe Total Ozone Mapping Spectrometer (TOMS) payload. These initial results look promising, with apparently good correlation between the two datasets. A novel, more-complex retrieval algorithm has been applied to the high-resolution data, and early results have shown agreement with the TOMS.     

Gramicidin Ion Channel-Based Biosensors: Construction, Stochastic Dynamical Models, and Statistical Detection Algorithms

This paper deals with the experimental construction, stochastic modeling, and statistical signal processing of a novel, artificially constructed biosensor comprised of biological ion channels. Such nanoscale biosensors have been built by incorporating dimeric gramicidin A (bis-gA) ion channels into bilayer membranes of giant unilamellar liposomes, and then excising small patches of the membrane loaded with ion channels. We present a stochastic model for the response of the biosensor and present statistical model validation tests to verify the adequacy of the model. We show that in the presence of specific target molecules, the statistics of the gating mechanisms of the gA channels are altered. By capturing the change in real time, we devise a maximum-likelihood detector to detect the presence of target molecules. To test the sensitivity of this model, we conducted patch-clamp experiments with two compounds known to inhibit conduction of the gA channels. We found experimentally that the real-time detection algorithm was able to accurately identify the addition of the compounds even when the alterations in the patch-clamp recordings were very small. This algorithm provides the sensitive detection system for ongoing development of lipid-based nanosensors.     

Industrial capacity planning in oligopolistic markets

Available productive capacity is determinant of a company’s success once it allows meeting the current and future demand. This article proposes a quantitative model for determining long-term productive capacity in competitive oligopolistic markets, based on the Nash Equilibrium formulated as a Variational Inequality problem. Numerical examples enable an analytical evaluation of the economic equilibrium’s sensitivity to marginal costs, investment costs, hurdle rate, and market saturation. Results show that, in order to achieve a greater market share, it is important to adopt strategies that reduce marginal costs. On the other hand, variations in the hurdle rate may or may not reinforce the position of a competitor in the market and his interest in investing in capacity expansion. Additionally, market saturation may be achieved, beyond which investment becomes unattractive. Each of these is a positive outcome for society, triggering diversified investments and competition in economic sectors where competition is low and profits are high.     

Effect of particle size on the shaping of ceramics by slip casting

The effect of the nanometric-ranged particle size of the starting powder through a simple and well-established shaping method, slip casting, has been studied. Several alumina suspensions with the same viscosity (but different solid content suspensions) and different particle size (11, 44, 190 and 600 nm) were prepared and shaped into a dense body. The green and sintered densities ranged between 30–67% and 63–99% of the theoretical value, respectively. These values, together with the microstructure observations reveal the effect of the solid content of the suspensions and the characteristics of the ceramic powder, leading to the determination of an optimal particle size. Based on both processability (rheological behaviour) and microstructure (density and grain size) it has been determined that particles with sizes ranging 100–300 nm are the best for preparing concentrated suspensions with low viscosity and bodies with density close to the theoretical value when using conventional pressureless sintering densification.     

In Vitro Simultaneous Transfer of Lipids to HDL in Coronary Artery Disease and in Statin Treatment

The exchange of lipids with cells and other lipoproteins is a crucial process in HDL metabolism and for HDL antiatherogenic function. Here, we tested a practical method to quantify the simultaneous transfer to HDL of phospholipids, free-cholesterol, esterified cholesterol and triacylglycerols and to verify the lipid transfer in patients with coronary artery disease (CAD) or undergoing statin treatment. Twenty-eight control subjects without CAD, 27 with CAD and 25 CAD patients under simvastatin treatment were studied. Plasma samples were incubated with a donor nanoemulsion prepared by ultrasonication of the constituent lipids and labeled with radioactive lipids; % lipids transferred to HDL were quantified in the HDL-containing supernatant after chemical precipitation of non-HDL fractions and the nanoemulsion. The assay was precise and reproducible. Increase of temperature (4–37 °C), of incubation period (5 min to 2 h), of HDL-cholesterol concentration (33–244 mg/dL) and of mass of nanoemulsion lipids (0.075–0.3 mg/μL) resulted in increased lipid transfer from the nanoemulsion to HDL. In contrast, increasing pH (6.5–8.5) and albumin concentration (3.5–7.0 g/dL) did not affect lipid transfer. There was no difference between CAD and control non-CAD with regard to the lipid transfer, but statin treatment reduced the transfer to HDL of all four lipids. The test herein described is a valid and practical tool for exploring an important aspect of HDL metabolism.