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Polychlorinated biphenyls (PCBs) remain chemicals of concern more than three decades after the ban on their production. Technical mixture-based total PCB measurements are unreliable due to weathering and degradation, while detailed full congener specific measurements can be time-consuming and costly for large studies. Measurements using a subset of indicator PCBs (iPCBs) have been considered appropriate; however, inclusion of different PCB congeners in various iPCB schemes makes it challenging to readily compare data. Here, using an extensive data set, we examine the performance of existing iPCB3 (PCB 138, 153, and 180), iPCB6 (iPCB3 plus 28, 52, and 101) and iPCB7 (iPCB6 plus 118) schemes, and new iPCB schemes in estimating total of PCB congeners (∑PCB) and dioxin-like PCB toxic equivalent (dlPCB-TEQ) concentrations in sport fish fillets and the whole body of juvenile fish. The coefficients of determination (R2) for regressions conducted using logarithmically transformed data suggest that inclusion of an increased number of PCBs in an iPCB improves relationship with ∑PCB but not dlPCB-TEQs. Overall, novel iPCB3 (PCB 95, 118, and 153), iPCB4 (iPCB3 plus 138) and iPCB5 (iPCB4 plus 110) presented in this study and existing iPCB6 and iPCB7 are the most optimal indicators, while the current iPCB3 should be avoided. Measurement of ∑PCB based on a more detailed analysis (50+ congeners) is also overall a good approach for assessing PCB contamination and to track PCB origin in fish. Relationships among the existing and new iPCB schemes have been presented to facilitate their interconversion. The iPCB6 equiv levels for the 6.5 and 10 pg/g benchmarks of dlPCB-TEQ05 are about 50 and 120 ng/g ww, respectively, which are lower than the corresponding iPCB6 limits of 125 and 300 ng/g ww set by the European Union.

A new method for yield optimization is presented that considers the high computational costs for circuit simulations and the typical parameter partitioning of integrated device models in deterministic and statistical parameters. It is based on a systematic concept for performance function macromodeling, that allows a flexible trade-off between simulation costs and modeling accuracy. Using quadratic performance models, an analytical expression for the yield gradient is derived by analyzing the performance statistics. Based on this yield gradient, an efficient deterministic optimization procedure will be proposed, which maintains the individual view of performance properties.

(1991). Long term development of phytoplankton in Lake Constance. SIL Proceedings, 1922-2010: Vol. 24, No. 2, pp. 826-830.

The effects of β-adrenoceptor agonists and antagonists on both the transmitter outflow and the associated pressure response produced by perivascular nerve stimulation have been studied in human digital arteries, in which transmitter stores were labelled with [3H]noradrenaline. Both isoprenaline and salbutamol at concentrations of 10−8–10−6 mol/l significantly enhanced stimulation-induced tritium outflow. These two agonists were approximately equipotent. Salbutamol also potentiated pressure responses to stimulation. Adrenaline, at a concentration of 10−8 mol/l, but not lower concentrations, produced a significant enhancement of the stimulation-induced tritium outflow which was associated with a small, but non-significant, potentiation of the pressure response to stimulation. Propranolol prevented the enhancement of stimulation-induced tritium outflow by salbutamol 10−7 mol/l and adrenaline 10−8 mol. Dobutamine 10−7 mol/l, but not 10−8 mol/l, significantly enhanced stimulation-induced tritium outflow. Resting outflow was markedly increased by higher concentrations of dobutamine. No potentiation of pressure responses to stimulation was produced by dobutamine. Propranolol and metoprolol had no effect on stimulation-induced transmitter outflow. Propranolol also had no effect on stimulation-induced outflow when the arteries were either perfused throughout the experiment with a low concentration of adrenaline or salbutamol, or when the arteries were preincubated in a high concentration of adrenaline as well as perfused throughout with a low concentration of adrenaline. Resting and stimulation-induced tritium outflow from arteries incubated in [3H]adrenaline was much lower and more variable than the outflow from arteries incubated in [3H]noradrenaline. It is concluded that facilitatory prejunctional β-adrenoceptors (probably of the β2-subtype) are present in human digital arteries, but that under the conditions of these experiments, neither transmitter noradrenaline, nor adrenaline that has been incorporated into transmitter stores with noradrenaline, activate these prejunctional β-adrenoceptors.

Inhibition of human erythrocyte acetylcholinesterase (AChE; EC 3.1.1.7) and serum butyrylcholinesterase (BChE; EC 3.1.1.8) by ethopropazine, 10-(2-diethylaminopropyl)phenothiazine hydrochloride, was measured with acetylthiocholine (ATCh) as substrate. Dissociation constants for the enzyme-inhibitor complexes were calculated from the effect of ATCh concentration on the apparent dissociation constants by applying non-linear regression to fit the model to experimental data. Inhibition of AChE revealed a competitive inhibition for two binding sites (Ka = 161 and Ki = 393 μmol dm-3), inhibition of the atypical BChE was non-competitive (Ki = 7.5 μmol dm-3) while that of the usual BChE was competitive (K(I) = 0.16 μmol dm-3). At the ethopropazine concentration of 20 μmol dm-3 and the acetyl-thiocholine concentration of 1.0 mmol dm-3 (conditions used for differentiation between AChE and BChE activities), the erythrocyte AChE was 8% inhibited and the BChE phenotypes UU, UA, FF/FS, AF, AJ/AK and AA/AS between 98% and 74%.

Background and purpose: Blood platelets represent an attractive peripheral model in neuropsychopharmacology owing to serotonin transmembrane uptake mechanism - target for different psychoactive drugs, mainly antidepressants. The transport kinetics of serotonin (5-hydroxytryptamine, 5HT) through the plasma membrane is interpreted by the Michaelis-Menten equation and results expressed in terms of Km and Vmax. Published values of kinetic parameters for the 5HT transport into rat platelets vary considerably. The purpose of this paper was to evaluate possible reasons of these varioations, with special emphasis given on methodology of kinetic measurements. Material and methods: Platelet rich plasma was separated from anticoagulated blood samples (1 mL) obtained by jugular venipuncture from ether-anesthetized rats. Kinetic measurements were performed at 37 C by incubating various number of rat platelets with several 14C-5HT concentrations during different time intervals. The uptake was terminated by rapid cooling of incubating mixture and separation of platelets by filtration at different vacuum settings. Platelet rich plasma was stored at room temperature for different time periods prior to kinetic measurements. Serotonin, taken up by platelets, was quantified as beta counts of 14C in liquid scintillator. Calculation of kinetic parameters, Km and Vmax, was performed using Eadie-Hofstee plot. Results: Based on the results of methodological studies, experimental conditions which, by our experience, assure reliable and reproducible kinetic measurements of 5HT tranasport into rat platelets were defined as follows: 1) concentration of platelets in incubating mixture: 25-30×10^6/uL of incubating medium ; b) concentrations of substrate (14C-5HT) in incubating medium: 0.05, 0.07, 0.10, 0.15, 0.25, 0.50 and 1.00 uM ; c) uptake interval: 30 seconds ; d) vacuum setting for filtration: 600 mmHg ; e) recommended storage of platelet suspension prior to kinetic determinations: up to three hours at room temperature. Values of kinetic parameters for serotonin uptake into rat platelets obtained by this methodology were: Vmax = 225 +/- 37 pmol 5HT ×10^8 plt/min and Km = 0.161 +/- 0.023 uM (M +/- SD, N = 27). Conclusion: Based on thorough methodological studies the procedure for reliable measurement of kinetic parameters of serotonin uptake into rat platelets was described with critical review of available literature in the field. Such methodology can serve as a basis for further development of the experimental model for ex vivo monitoring of platelet serotonin uptake in rats.

This note describes a magnetic stirring system, which can be installed inside high‐pressure autoclaves. Pressures up to 4 kilobar are possible and gaseous or liquid pressurizing media can be used. The stirrer moves a magnetic stirring bar inside the sample cell in a vertical direction. Owing to its simple and efficient design, thermal side effects are very small. The effectiveness of the stirrer is demonstrated by following the rate of solution of PbCl2 in water at various pressures.

Dechlorane Plus (DP) is a chlorinated flame retardant used in wire coatings, furniture and hard plastic connectors in computer monitors. It is manufactured in high volumes with production facilities located in the United States and China bringing into question whether the flame retardant existed in the environment. DP was detected in Lake Ontario sediments at concentrations 60-fold greater than in Lake Erie sediments; the maximum values were 586 ng g-1 and 8.6 ng g-1, respectively. These data suggest there is DP source into the Niagara River, which contributed to Lake Ontario’s DP burden. Analyses of Lake Ontario sediment core slices showed that recent concentrations were two orders of magnitude less than the core’s maximum concentration of 920 ng g-1 (1976-1980). New chemicals related to DP were also found in this core which DP’s profile, suggesting these compounds maybe impurities or side products in the manufacture of DP. The concentrations of one of the mono Diels-Alder adducts, 1,3-DPMA, was found in Lake Ontario lake trout to be two orders of magnitude greater than that of DP, suggesting the monoadduct is more bioaccumulative than DP. Analysis of a Lake Ontario food web illustrated that 1,3-DPMA was being diluted up the food chain, much like DP, while a second monoadduct, 1,5-DPMA was only detected in lower trophic species. In vitro lake trout liver microsomal exposures to the individual DPMA isomers showed that the depletion rate constant for 1,3- and 1,5-DPMA were 0.34 and 0.84 h-1, respectively, with corresponding t1/2’s of 2.02 ± 0.50 and 0.83 ± 0.18 h, respectively. The shorter 1,5-DPMA half-life was ascribed to the unsterically hindered double bond which allowed for greater enzyme attack. Dechlorination of DP was observed during the analysis of sediment extracts and was attributed as being an artefact of dirty injector liners; care needs to be taken to insure this dechlorination does not occur during analysis of environmental samples. This was important as dechlorinated DP products were observed in Lake Ontario sediment and core extracts. DP was shown to be a worldwide airborne contaminant from analysis of passive samplers over a period of one year. The maximum concentration was detected in Delhi, India (226 pg m-3). Middle Eastern and Indo-Asian regions exhibited the greatest concentrations in the world providing likely the result of other DP manufactures and/or that the practice of open pit burning of wires and cables was adding to the regions air burden. Doctor of Philosophy (PhD)