Similar bioavailability of single-dose oral and intravenous mesna in the blood and urine of healthy human subjects

Although mesna has been used for more than a decade to reduce the incidence of hemorrhagic cystitis induced by ifosfamide and cyclophosphamide, the disposition of i.v. and oral mesna has not been adequately described. To obtain accurate bioavailability data for the design of mesna regimens, we developed procedures to preserve and measure mesna and dimesna in the blood and urine and studied 25 volunteer subjects who received single doses of i.v. mesna and four different formulations of oral mesna in a five-way randomized crossover study. The dose-adjusted area under the blood concentration-time curve showed no difference in bioavailability for i.v. and oral mesna; however, the maximum mesna concentration after oral doses was 16% of that estimated for i.v. doses. The short initial half-life of i.v. mesna indicated that mesna was rapidly cleared; however, the blood concentrations of mesna uniformly exceeded those of dimesna after oral as well as i.v. doses, which suggested that reduced mesna and oxidized mesna disulfide are in equilibrium. The ratio of mesna:dimesna was higher in protein-free plasma than it was in the urine, which suggested that most urinary mesna is produced by glomerular filtration of mesna rather than by renal tubular reduction of dimesna. The sum of mesna and dimesna excretion after the i.v. doses (73% of the dose) and the four oral formulations (68-73%) showed no difference in urinary bioavailability, consistent with the blood data. However, the urinary bioavailability of the therapeutically active free-thiol mesna was greater after i.v. doses (40% of the dose) than it was after oral doses (31-33%). The ratio of oral:i.v. mesna excretion ranged from 0.52-1.23 (mean, 0.82) among the 24 subjects. Urinary mesna concentrations exceeded 50 microM in all subjects for up to 12 h after oral doses as compared to 4 h after i.v. doses. About 90% of this mesna was excreted by hour 2 after i.v. doses and by hour 9 after oral doses. The mean maximum concentration of mesna in blood and excretion into urine were both 2.6 h after dosing. The oral formulations thus showed sustained urinary excretion, and their urinary bioavailability approached that of i.v. mesna.     

Simulating colliding flows in smoothed particle hydrodynamics with fractional derivatives

We propose a new method based on the use of fractional differentiation for improving the efficiency and realism of simulations based on smoothed particle hydrodynamics (SPH). SPH represents a popular particle‐based approach for fluid simulation and a high number of particles is typically needed for achieving high quality results. However, as the number of simulated particles increase, the speed of computation degrades accordingly. The proposed method employs fractional differentiation to improve the results obtained with SPH in a given resolution. The approach is based on the observation that effects requiring a high number of particles are most often produced from colliding flows, and therefore, when the modeling of this behavior is improved, higher quality results can be achieved without changing the number of particles being simulated. Our method can be employed to reduce the resolution without significant loss of quality, or to improve the quality of the simulation in the current chosen resolution. The advantages of our method are demonstrated with several quantitative evaluations. Copyright © 2013 John Wiley & Sons, Ltd.     

Recent Developments in Friction Stir Welding of Al-alloys

The diversity and never-ending desire for a better life standard result in a continuous development of the existing manufacturing technologies. In line with these developments in the existing production technologies the demand for more complex products increases, which also stimulates new approaches in production routes of such products, e.g., novel welding procedures. For instance, the friction stir welding (FSW) technology, developed for joining difficult-to-weld Al-alloys, has been implemented by industry in manufacturing of several products. There are also numerous attempts to apply this method to other materials beyond Al-alloys. However, the process has not yet been implemented by industry for joining these materials with the exception of some limited applications. The microstructures and mechanical properties of friction stir welded Al-alloys existing in the open literature will be discussed in detail in this review. The correlations between weld parameters used during FSW and the microstructures evolved in the weld region and thus mechanical properties of the joints produced will be highlighted. However, the modeling studies, material flow, texture formation and developments in tool design are out of the scope of this work as well as the other variants of this technology, such as friction stir spot welding (FSSW).     

A Photovoltaic C60-Si Heterojunction

Abstract

A heterojunction was prepared by depositing a thin film of C₆₀ on a p-Si substrate. Photovoltaic properties were observed using a UV-filtered solar simulator and natural sun light. Surface Photovoltage Spectroscopy was employed to distinguish between the nature of photoconversion in the C₆₀ and Si layers.     

A mathematical approach for integrating the cell design and production planning decisions

A mixed integer programming model that selects cells that can handle demand variability is presented. Valid inequalities are added to the linear programming relaxation of the model. By adding these valid inequalities, the lower bound on the model's optimal objective function value is significantly improved. An efficient heuristic procedure that generates good solutions to this model is also presented.     

Near ground propagation model for pine tree forest environment

A propagation model experimentally derived from both free space and near ground plane earth path loss models for pine tree forest with foliage depth lower than 400 m has been proposed. It is a piecewise model taking foliage depth of 200 m as a boundary. The model is compared with several well-known models, namely Weissberger, ITU-R and COST235. Different from other models, the proposed one takes into account trunk height gain k. Observed average error is about 6 dB for proposed model whereas it is about 32 dB, 16 dB and 20 dB for COST235, Weissberger and ITU-R models, respectively. Also, it is observed that COST235 estimates the highest path loss among the models and it has the highest absolute errors especially in a forest with low foliage density.     

Arsenite removal from groundwater in a batch electrocoagulation process: Optimization through response surface methodology

In this study, influences of seven process variables such as initial pH (pH_i), applied current (i), operating time (t_EC), initial As(III) concentration (C_o), diameter of Fe ball anode (d_p), column height in the electrocoagulation (EC) reactor (h) and airflow rate (Q_air) for removal of As(III) from groundwater by a new air-fed fixed-bed EC reactor were evaluated with a response surface methodology (RSM). The proposed quadratic model fitted very well with the experimental data for the responses. The removal efficiencies and operating costs were determined to be 99% and 0.01 $/m³ at the optimum operating conditions (a pH_i of 8.5, 0.05 A, 4.94 min, d_p of 9.24 mm, h of 7.49 cm, Q_air of 9.98 L/min for 50 µg/L). This study clearly showed that the RSM in the EC process was a very suitable method to optimize the operating conditions at the target value of effluent As(III) concentration (10 µg/L) while keeping the operating cost to minimal and maximize the removal efficiency.     

A neural network-based approach for calculating dissolved oxygen profiles in reservoirs

A Neural Network (NN) modelling approach has been shown to be successful in calculating pseudo steady state time and space dependent Dissolved Oxygen (DO) concentrations in three separate reservoirs with different characteristics using limited number of input variables. The Levenberg–Marquardt algorithm was adopted during training. Pre-processing before training and post processing after simulation steps were the treatments applied to raw data and predictions respectively. Generalisation was improved and over-fitting problems were eliminated: Early stopping method was applied for improving generalisation. The correlation coefficients between neural network estimates and field measurements were as high as 0.98 for two of the reservoirs with experiments that involve double layer neural network structure with 30 neurons within each hidden layer. A simple one layer neural network structure with 11 neurons has yielded comparable and satisfactorily high correlation coefficients for complete data set, and training, validation and test sets of the third reservoir.