Cardioinotropic Effects in Subchronic Intoxication of Rats with Lead and/or Cadmium Oxide Nanoparticles

Subchronic intoxication was induced in outbred male rats by repeated intraperitoneal injections with lead oxide (PbO) and/or cadmium oxide (CdO) nanoparticles (NPs) 3 times a week during 6 weeks for the purpose of examining its effects on the contractile characteristics of isolated right ventricle trabeculae and papillary muscles in isometric and afterload contractions. Isolated and combined intoxication with these NPs was observed to reduce the mechanical work produced by both types of myocardial preparation. Using the in vitro motility assay, we showed that the sliding velocity of regulated thin filaments drops under both isolated and combined intoxication with CdO–NP and PbO–NP. These results correlate with a shift in the expression of myosin heavy chain (MHC) isoforms towards slowly cycling β–MHC. The type of CdO–NP + PbO–NP combined cardiotoxicity depends on the effect of the toxic impact, the extent of this effect, the ratio of toxicant doses, and the degree of stretching of cardiomyocytes and muscle type studied. Some indices of combined Pb–NP and CdO–NP cardiotoxicity and general toxicity (genotoxicity included) became fully or partly normalized if intoxication developed against background administration of a bioprotective complex.     

X-ray Fluorescence Uptake Measurement of Functionalized Gold Nanoparticles in Tumor Cell Microsamples

Quantitative cellular in vitro nanoparticle uptake measurements are possible with a large number of different techniques, however, all have their respective restrictions. Here, we demonstrate the application of synchrotron-based X-ray fluorescence imaging (XFI) on prostate tumor cells, which have internalized differently functionalized gold nanoparticles. Total nanoparticle uptake on the order of a few hundred picograms could be conveniently observed with microsamples consisting of only a few hundreds of cells. A comparison with mass spectroscopy quantification is provided, experimental results are both supported and sensitivity limits of this XFI approach extrapolated by Monte-Carlo simulations, yielding a minimum detectable nanoparticle mass of just 5 pg. This study demonstrates the high sensitivity level of XFI, allowing non-destructive uptake measurements with very small microsamples within just seconds of irradiation time.     

CYP154C5 Regioselectivity in Steroid Hydroxylation Explored by Substrate Modifications and Protein Engineering**

CYP154C5 from Nocardia farcinica is a P450 monooxygenase able to hydroxylate a range of steroids with high regio- and stereoselectivity at the 16α-position. Using protein engineering and substrate modifications based on the crystal structure of CYP154C5, an altered regioselectivity of the enzyme in steroid hydroxylation had been achieved. Thus, conversion of progesterone by mutant CYP154C5 F92A resulted in formation of the corresponding 21-hydroxylated product 11-deoxycorticosterone in addition to 16α-hydroxylation. Using MD simulation, this altered regioselectivity appeared to result from an alternative binding mode of the steroid in the active site of mutant F92A. MD simulation further suggested that the entrance of water to the active site caused higher uncoupling in this mutant. Moreover, exclusive 15α-hydroxylation was observed for wild-type CYP154C5 in the conversion of 5α-androstan-3-one, lacking an oxy-functional group at C17. Overall, our data give valuable insight into the structure–function relationship of this cytochrome P450 monooxygenase for steroid hydroxylation.     

Different measures of sensitivity of recipe colour to random and proportional dye concentration error. Part 2: An example of target-position dependence and span

A regularity of the predicted sensitivities to random and proportional dye concentration errors in regard to the position of target colour has been observed for the case of dyeing acrylic with basic dyes. The sensitivity of the recipe colour to random dye concentration errors is highest for light neutral target colours and is almost negligible for dark-shade recipes. Recipes for less saturated targets are slightly more sensitive than recipes for more saturated targets of equal lightness. The span of the sensitivities to weighing error of the recipes matching a given target varies with the position of the target in colour space. By contrast, the sensitivity of recipes to dye strength error is the highest at medium to low lightness for neutral and near neutral target shades. The span of sensitivities of the recipes for any such particular target is broad, with some having low sensitivity to strength errors. Recipes for the target colours at the 'lighter' part of the gamut border were the least sensitive to strength errors. Received: 10 June 2005; Accepted: 11 July 2005.     

Polynomial-Time Algorithms for Energy Games with Special Weight Structures

Energy games belong to a class of turn-based two-player infinite-duration games played on a weighted directed graph. It is one of the rare and intriguing combinatorial problems that lie in NP∩co-NP, but are not known to be in P. The existence of polynomial-time algorithms has been a major open problem for decades and apart from pseudopolynomial algorithms there is no algorithm that solves any non-trivial subclass in polynomial time. In this paper, we give several results based on the weight structures of the graph. First, we identify a notion of penalty and present a polynomial-time algorithm when the penalty is large. Our algorithm is the first polynomial-time algorithm on a large class of weighted graphs. It includes several worst-case instances on which previous algorithms, such as value iteration and random facet algorithms, require at least sub-exponential time. Our main technique is developing the first non-trivial approximation algorithm and showing how to convert it to an exact algorithm. Moreover, we show that in a practical case in verification where weights are clustered around a constant number of values, the energy game problem can be solved in polynomial time. We also show that the problem is still as hard as in general when the clique-width is bounded or the graph is strongly ergodic, suggesting that restricting the graph structure does not necessarily help.     

Synthesis of polymer materials for use as cell culture substrates

Up to today, several techniques have been used to maintain cells in culture for studying many aspects of cell biology and physiology. More often, cell culture is dependent on proper anchorage of cells to the growth surface. Thus, poly-l-lysine, fibronectin or laminin are the most commonly used substrates. In this study, electrosynthesized biocompatible polymer films are proposed as an alternative to these standard substrates. The electrosynthesized polymers tested were polyethylenimine, polypropylenimine and polypyrrole. Then, the adhesion, proliferation and morphology of rat neuronal cell lines were investigated on these polymer substrates in an attempt to develop new and efficient polymer materials for cell culture. During their growth on the polymers, the evolution of the cell morphology was monitored using both confocal microscopy and immunohistochemistry, leading to the conclusion of a normal development. An estimation of the adhesion and proliferation rates of rat neuronal cell cultures indicated that polyethylenimine and polypropylenimine were the best substrates for culturing olfactory neuronal cells. A method to favour the differentiation of the neuronal cells was also developed since the final aim of this work is to develop a biosensor for odour detection using differentiated neuronal cells as transducers. Consequently, a biosensor was microfabricated using silicon technology. This microsystem allowed us to culture the cells on a silicon wafer and to position the cells on certain parts of the silicon wafer.     

Evaluation of two cooling systems under a firefighter coverall

Firemen often suffer from heat strain. This study investigated two chest cooling systems for use under a firefighting suit. In nine male subjects, a vest with water soaked cooling pads and a vest with water perfused tubes were compared to a control condition. Subjects performed 30 min walking and 10 min recovery in hot conditions, while physiological and perceptual parameters were measured. No differences were observed in heart rate and rectal temperature, but scapular skin temperature and fluid loss were lower using the perfused vest. Thermal sensation was cooler for the perfused vest than for the other conditions, while the cool pad vest felt initially cooler than control. However, comfort and RPE scores were similar. We conclude that the cooling effect of both tested systems, mainly providing a (temporally) cooler thermal sensation, was limited and did not meet the expectations.     

The effect of pre-warming on performance during simulated firefighting exercise

This study examined the effect of active pre-warming on speed and quality of performance during simulated firefighting exercise. Twelve male firefighters performed two trials in counterbalanced order. They were either pre-warmed by 20-min cycling at 1.5 Watt kg⁻¹ body mass (WARM) or remained thermoneutral (CON) prior to a simulated firefighting activity. After the pre-warming, gastrointestinal temperature (P < 0.001), skin temperature (P = 0.002), and heart rate (P < 0.001) were higher in WARM than in CON. During the firefighting activity, rating of perceived exertion, thermal sensation and discomfort were higher for WARM than for CON. Finish time of the firefighting activity was similar, but the last task of the activity was completed slower in WARM than in CON (P = 0.04). In WARM, self-reported performance quality was lower than in CON (P = 0.04). It is concluded that pre-warming reduces the speed during the last part of simulated firefighting activity and reduces self-reported quality of performance.