In Vitro Release Behavior of Toremifene Citrate from Sol-Gel Processed Sintered Silica Xerogels

Factors affecting the adsorption and desorption of toremifene citrate (TC) on sintered silica xerogels were investigated in vitro. TC was attached onto sol-gel processed sintered silica xerogel grains or disks by adsorption. The adsorption of TC on the surface of silica was pH dependent. The results support the conclusion that large pore size results in highest drug adsorption. Adsorption of TC was most effective in xerogels sintered at 700°C and containing the largest pores and lowest specific surface area of the silica xerogels studied in the adsorption tests. The release of TC from the xerogel matrix was linear with respect to the square root of time. The release of TC from the grains was very rapid for the first 5 hr, followed by a slower release. All drug was released from the grains, and 60% to 80% was released from the disks in 24 hr. All drug-silica xerogel formulations showed sustained in vitro release profiles.     

Effects of intraruminal infusions of propionate and butyrate with two different protein supplements on milk production and blood metabolites in dairy cows receiving grass silage-based diet

Four cows were used in a balanced 4×4 Latin square with 2 week experimental periods to investigate the effects of intraruminal infusions of volatile fatty acids and protein source on milk production and blood metabolites. The four treatments in a 2×2 factorial arrangement were isoenergetic intraruminal infusions of propionate (500 g day⁻¹) or butyrate (417 g day⁻¹) each given with isonitrogenous protein supplementation of fish meal (FM) or barley protein (BP). The cows were fed restrictively with 9 kg dry matter day⁻¹ of formic acid treated grass silage and 8 kg day⁻¹ of concentrate. Propionate infusion increased milk yield (24·9 vs 23·4 kg day⁻¹; P<0·05), milk protein yield (832 vs 778 g day⁻¹; P=0·05) and milk lactose content (44·7 vs 43·5 g kg⁻¹; P<0·05) and yield (1113 vs 1023 g day⁻¹; P<0·01), whereas butyrate infusion was associated with a higher milk fat content (44·7 vs 39·4 g kg⁻¹; P<0·01) and yield (1033 vs 974 g day⁻¹; P<0·01). FM tended (P<0·10) to increase milk yield, but had no significant effects on milk composition or milk component yields compared with BP. Butyrate infusion increased blood ketones, plasma non-esterified fatty acids and glycine relative to propionate infusion. The concentrations of ammonia N in rumen fluid and urea in plasma and milk were similar for both protein supplements. The profile of amino acids in plasma was similar for both protein supplements except for the higher concentrations of phenylalanine, proline and tyrosine with BP. The results show that protein utilisation can be improved by increasing the supply of propionate from rumen fermentation in cows given a grass silage-based diet. © 1998 SCI.     

Deletion of Col15a1 Modulates the Tumour Extracellular Matrix and Leads to Increased Tumour Growth in the MMTV-PyMT Mouse Mammary Carcinoma Model

Basement membrane (BM) zone-associated collagen XV (ColXV) has been shown to suppress the malignancy of tumour cells, and its restin domain can inhibit angiogenesis. In human breast cancer, as well as in many other human carcinomas, ColXV is lost from the epithelial BM zone prior to tumour invasion. Here, we addressed the roles of ColXV in breast carcinogenesis using the transgenic MMTV-PyMT mouse mammary carcinoma model. We show here for the first time that the inactivation of Col15a1 in mice leads to changes in the fibrillar tumour matrix and to increased mammary tumour growth. ColXV is expressed by myoepithelial and endothelial cells in mammary tumours and is lost from the ductal BM along with the loss of the myoepithelial layer during cancer progression while persisting in blood vessels and capillaries, even in invasive tumours. However, despite the absence of anti-angiogenic restin domain, neovascularisation was reduced rather than increased in the ColXV-deficient mammary tumours compared to controls. We also show that, in robust tumour cell transplantation models or in a chemical-induced fibrosarcoma model, the inactivation of Col15a1 does not affect tumour growth or angiogenesis. In conclusion, our results support the proposed tumour suppressor function of ColXV in mammary carcinogenesis and reveal diverse roles of this collagen in different cancer types.     

Characteristics of nFOG,an aerosol-based wet thin film coating technique

An atmospheric pressure aerosol-based wet thin film coating technique called the nFOG is characterized and applied in polymer film coatings. In the nFOG, a fog of droplets is formed by two air-assist atomizers oriented toward each other inside a deposition chamber. The droplets settle gravitationally and deposit on a substrate, forming a wet film. In this study, the continuous deposition mode of the nFOG is explored. We determined the size distribution of water droplets inside the chamber in a wide side range of 0.1–100 µm and on the substrate using aerosol measurement instruments and optical microscopy, respectively. The droplet size distribution was found to be bimodal with droplets of approximately 30–50 µm contributing the most to the mass of the formed wet film. The complementary measurement methods allow us to estimate the role of different droplet deposition mechanisms. The obtained results suggest that the deposition velocity of the droplets is lower than the calculated terminal settling velocity, likely due to the flow fields inside the chamber. Furthermore, the mass flux of the droplets onto the substrate is determined to be in the order of 1 g/m³s, corresponding to a wet film growth rate of 1 µm/s. Finally, the nFOG technique is demonstrated by preparing polymer films with thicknesses in the range of approximately 0.1–20 µm.     

Unrestricted vs restricted cut in a tableau method for Boolean circuits

This paper studies the relative efficiency of variations of a tableau method for Boolean circuit satisfiability checking. The considered method is a nonclausal generalisation of the Davis–Putnam–Logemann–Loveland (DPLL) procedure to Boolean circuits. The variations are obtained by restricting the use of the cut (splitting) rule in several natural ways. It is shown that the more restricted variations cannot polynomially simulate the less restricted ones. For each pair of methods T, T′, an infinite family of circuits is devised for which T has polynomial size proofs while in T′ the minimal proofs are of exponential size w.r.t. n, implying exponential separation of T and T′ w.r.t. n. The results also apply to DPLL for formulas in conjunctive normal form obtained from Boolean circuits by using Tseitin’s translation. Thus DPLL with the considered cut restrictions, such as allowing splitting only on the variables corresponding to the input gates, cannot polynomially simulate DPLL with unrestricted splitting.AMS subject classification 03B70, 03F20, 68T15, 68T20The financial support from Academy of Finland (project #53695) is gratefully acknowledged.Tommi Junttila: This work was partially done while visiting ITC-IRST (Trento, Italy), and has been sponsored by the CALCULEMUS! IHP-RTN EC project, contract code HPRN-CT-2000-00102.     

Independent finite automata on Cayley graphs

In the setting of symbolic dynamics on discrete finitely generated infinite groups, we define a model of finite automata with multiple independent heads that walk on Cayley graphs, called group-walking automata, and use it to define subshifts. We characterize the torsion groups (also known as periodic groups) as those on which the group-walking automata are strictly weaker than Turing machines, and those on which the head hierarchy is infinite.     

Preparation and characterization of collagen/PLA,chitosan/PLA,and collagen/chitosan/PLA hybrid scaffolds for cartilage tissue engineering

In this study, three-dimensional (3D) porous scaffolds were developed for the repair of articular cartilage defects. Novel collagen/polylactide (PLA), chitosan/PLA, and collagen/chitosan/PLA hybrid scaffolds were fabricated by combining freeze-dried natural components and synthetic PLA mesh, where the 3D PLA mesh gives mechanical strength, and the natural polymers, collagen and/or chitosan, mimic the natural cartilage tissue environment of chondrocytes. In total, eight scaffold types were studied: four hybrid structures containing collagen and/or chitosan with PLA, and four parallel plain scaffolds with only collagen and/or chitosan. The potential of these types of scaffolds for cartilage tissue engineering applications were determined by the analysis of the microstructure, water uptake, mechanical strength, and the viability and attachment of adult bovine chondrocytes to the scaffolds. The manufacturing method used was found to be applicable for the manufacturing of hybrid scaffolds with highly porous 3D structures. All the hybrid scaffolds showed a highly porous structure with open pores throughout the scaffold. Collagen was found to bind water inside the structure in all collagen-containing scaffolds better than the chitosan-containing scaffolds, and the plain collagen scaffolds had the highest water absorption. The stiffness of the scaffold was improved by the hybrid structure compared to plain scaffolds. The cell viability and attachment was good in all scaffolds, however, the collagen hybrid scaffolds showed the best penetration of cells into the scaffold. Our results show that from the studied scaffolds the collagen/PLA hybrids are the most promising scaffolds from this group for cartilage tissue engineering.     

Flash smelting and converting furnaces: A 50 year retrospect

1999 marked the 50th anniversary of the Outokumpu flash-smelting process. Originating during the post-World War II energy crisis, flash smelting is a high-intensity process developed to attain ever-increasing throughputs and intensities. Many innovations and continuous development ensued during the next 50 years before today’s state-of-the-art copper-making process chain and environmental benchmarking technology (e.g., Outokumpu flash smelting, Kennecott-Outokumpu flash converting, and flash technology) became possible. This article reviews how Outokumpu flash furnace design, especially cooling for higher heat loads, has improved over the years. For more information, contact I.V. Kojo, Outokumpu Engineering Contractors Oy, P.O. Box 862, FIN-02201 Espoo, Finland; telephone 358-9-4211; fax 358-9-421 3973; e-mail ilkka.kojo@outokumpu.com.     

Removal of cyanobacteria, cyanotoxins, heterotrophic bacteria and endotoxins at an operating surface water treatment plant.

The removal of cyanobacteria, hepatotoxins produced by them (microcystins), phytoplankton, heterotrophic bacteria and endotoxins were monitored at a surface water treatment plant with coagulation, clarification, sand filtration, ozonation, slow sand filtration and chlorination as the treatment process. Coagulation-sand filtration reduced microcystins by 1.2-2.4, and endotoxins by 0.72-2.01 log10 units. Ozonation effectively removed the residual microcystins. The treatment process reduced phytoplankton biomass by 2.2-4.6 and heterotrophic bacteria by 2.0-5.0 log10 units. In treated water, the concentration of microcystins never exceeded the WHO guide value (1 microg/L), but picoplankton and monad cells were often detected in high numbers. The heterotrophic bacterial isolates from the treated waters belonged to genera Sphingomonas, Pseudomonas, Bacillus, Herbaspirillum and Bosea.