Assessing the potential of pharmaceuticals and their transformation products to cause mutagenic effects: Implications for gene expression profiling.

The selection and prioritization of pharmaceuticals and their transformation products for evaluating effects on the environment and human health is a challenging task. One common approach is based on compounds (e.g., mixture composition, concentrations), and another on biology (e.g., relevant endpoint, biological organizational level). Both of these approaches often resemble a Lernaean Hydra-they can create more questions than answers. The present study embraces this complexity, providing an integrated approach toward assessing the potential effects of transformation products of pharmaceuticals by means of mutagenicity, estrogenicity, and differences in the gene expression profiles. Mutagenicity using the tk kinase assay was applied to assess a list of 11 priority pharmaceuticals, namely, atenolol, azithromycin, carbamazepine, diclofenac, ibuprofen, erythromycin, metoprolol, ofloxacin, propranolol, sulfamethoxazole, and trimethoprim. The most mutagenic compounds were found to be ß-blockers. In parallel, the photolabile pharmaceuticals were assessed for their mixture effects on mutagenicity (tk assay), estrogenicity (T47D- KBluc assay), and gene expression (microarrays). Interestingly, the mixtures were mutagenic at the µg/L level, indicating a synergistic effect. None of the photolysed mixtures were statistically significantly estrogenic. Gene expression profiling revealed effects related mainly to certain pathways, those of the p53 gene, mitogen-activated protein kinase, alanine, aspartate, and glutamate metabolism, and translation-related (spliceosome). Fourteen phototransformation products are proposed based on the m/z values found through ultra-performance liquid chromatography-tandem mass spectrometry analysis. The transformation routes of the photolysed mixtures indicate a strong similarity with those obtained for each pharmaceutical separately. This finding reinforces the view that transformation products are to be expected in naturally occurring mixtures. Environ Toxicol Chem 2016;35:2753-2764. © 2016 SETAC.

Technical Note: On the proton range and nuclear interactions in compounds and mixtures.

PURPOSE: Range and probability of nonelastic nuclear interactions (NNIs) for protons can be found only for a limited number of compounds and mixtures in nuclear data tables, and the proton-related analytical studies are therefore restricted to those materials for which the data are provided in these documents. In this paper, the authors present general solutions for calculating the proton range and probability of NNIs for desired compounds and mixtures. METHODS: Benefiting from the Bragg-Kleeman approximation of mass stopping power, the authors derive a concise formula for calculating the proton range in materials with arbitrary number of constituent elements. Additionally, the authors propose another relation for obtaining the probability of undergoing NNIs which is suggested to be additive. RESULTS: The examination of the formula presented shows that the authors' method can be considered as general solutions for analytical evaluation of the range in compounds and mixtures. The formula proposed for probability of NNIs is valid for almost every compound except for those materials containing H. It is shown that this formula can be modified so that it covers these materials. CONCLUSIONS: The authors present a general analytical method for calculating the range and probability of NNIs for protons which are mathematically easy to handle and valid for desired compounds or mixtures composed of an arbitrary number of constituent elements, including materials of interest for proton radiotherapy purposes.

Removal of a mixture tetracycline-tylosin from water based on anodic oxidation on a glassy carbon electrode coupled to activated sludge.

The purpose of this study was first to examine the electrochemical oxidation of two antibiotics, tetracycline (TC) and tylosin (Tylo), considered separately or in mixture, on a glassy carbon electrode in aqueous solutions; and then to assess the relevance of such electrochemical process as a pre-treatment prior to a biological treatment (activated sludge) for the removal of these antibiotics. The influence of the working potential and the initial concentration of TC and Tylo on the electrochemical pre-treatment process was also investigated. It was noticed that antibiotics degradation was favoured at high potential (2.4 V/ saturated calomel electrode (SCE)), achieving total degradation after 50 min for TC and 40 min for Tylo for 50 mg L(-1) initial concentration, with a higher mineralization efficiency in the case of TC. The biological oxygen demand in 5 days (BOD5)/Chemical oxygen demand (COD) ratio increased substantially, from 0.033 to 0.39 and from 0.038 to 0.50 for TC and Tylo, respectively. Regarding the mixture (TC and Tylo), the mineralization yield increased from 10.6% to 30.0% within 60 min of reaction time when the potential increased from 1.5 to 2.4 V/SCE and the BOD5/COD ratio increased substantially from 0.010 initially to 0.29 after 6 h of electrochemical pre-treatment. A biological treatment was, therefore, performed aerobically during 30 days, leading to an overall decrease of 72% of the dissolved organic carbon by means of the combined process.

Dynamics and electrorheology of sheared immiscible fluid mixtures.

We analyze the electrorheological effect in immiscible fluid mixtures with dielectric mismatch. By taking the electric field effect into account, which couples to the dynamics of domain morphology under flow, we propose a set of electrorheological constitutive equations valid under the condition where the relative magnitude of the flow field is stronger than that of the electric field. Through comparison with recent experiments, we point out a unique dynamical stress response inherent in situations where the cross-coupling between different fields is essential.

Photo-Fenton degradation of phenol, 2,4-dichlorophenoxyacetic acid and 2,4-dichlorophenol mixture in saline solution using a falling-film solar reactor.

In this work, a saline aqueous solution of phenol, 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4-dichlorophenol (2,4-DCP) was treated by the photo-Fenton process in a falling-film solar reactor. The influence of the parameters such as initial pH (5-7), initial concentration of Fe2+ (1-2.5mM) and rate of H202 addition (1.87-3.74mmol min-1) was investigated. The efficiency of photodegradation was determined from the removal of dissolved organic carbon (DOC), described by the species degradation of phenol, 2,4-D and 2,4-DCP. Response surface methodology was employed to assess the effects of the variables investigated, i.e. [Fe2+], [H202] and pH, in the photo-Fenton process with solar irradiation. The results reveal that the variables' initial concentration of Fe2+ and H202 presents predominant effect on pollutants' degradation in terms of DOC removal, while pH showed no influence. Under the most adequate experimental conditions, about 85% DOC removal was obtained in 180 min by using a reaction system employed here, and total removal of phenol, 2,4- and 2,4-DCP mixture in about 30min.

Photo-bio-synthesis of irregular shaped functionalized gold nanoparticles using edible mushroom Pleurotus florida and its anticancer evaluation.

A green chemistry approach to the synthesis of gold nanoparticles using edible mushroom Pleurotus florida (Oyster mushroom) by photo-irradiation method has been attempted. The mixture containing the aqueous gold ions and the mushroom extract was exposed to sunlight; this resulted in the formation of biofunctionalized gold nanoparticles. These nanoparticles were characterized using various techniques like UV-visible spectroscopy; X-ray diffraction studies, Energy dispersive X-ray analysis, Field emission scanning electron microscopy, Atomic force microscopy, Transmission electron microscopy and Fourier transform infrared spectrometry. The obtained biofunctionalized gold nanoparticles showed effective anti-cancer property against four different cancer cell lines A-549 (Human lung carcinoma), K-562 (Human chronic myelogenous leukemia bone marrow), HeLa (Human cervix) and MDA-MB (Human adenocarcinoma mammary gland) and no lethal effect is observed in Vero (African green monkey kidney normal cell) cell lines.

Antagonistic flexoelectric response in liquid crystal mixtures of bent-core and rodlike molecules.

We report the measurements of the temperature variations of the flexoelastic coefficient (e(*)/K) of a host calamitic liquid crystal (RO) and its mixture with two guest bent-core (BC-120 and BC-60) liquid crystals. The bent-core (BC) molecules have different core structures and bend angles; namely, θ=/~120° and =/~60°, respectively. We find that e(*)/K is independent of temperature and decreases rapidly with increasing concentration of BC-120 molecules and changes sign from positive to negative. In mixtures with BC-60, e(*)/K is always positive and its concentration-dependent variation is not unique. At 7M% it is significantly large (three times) near the nematic-isotropic transition and decreases strongly with reducing temperature. Dielectric measurement suggests antagonistic orientation of the dipole axes (arrow axes) of the two BC molecules in the host liquid crystal, and based on this, the opposite sign of e(*)/K is explained.

Soft cutting of single-wall carbon nanotubes by low temperature ultrasonication in a mixture of sulfuric and nitric acids.

To decrease single-wall carbon nanotube (SWCNT) lengths to a value of 100-200 nm, aggressive cutting methods, accompanied by a high loss of starting material, are frequently used. We propose a cutting approach based on low temperature intensive ultrasonication in a mixture of sulfuric and nitric acids. The method is nondestructive with a yield close to 100%. It was applied to cut nanotubes produced in three different ways: gas-phase catalysis, chemical vapor deposition, and electric-arc-discharge methods. Raman and Fourier transform infrared spectroscopy were used to demonstrate that the cut carbon nanotubes have a low extent of sidewall degradation and their electronic properties are close to those of the untreated tubes. It was proposed to use the spectral position of the far-infrared absorption peak as a simple criterion for the estimation of SWCNT length distribution in the samples.

A multiplexed separation of iron oxide nanocrystals using variable magnetic fields.

The size-dependent magnetic properties of nanocrystals are exploited in a separation process that distinguishes particles based on their diameter. By varying the magnetic field strength, four populations of magnetic materials were isolated from a mixture. This separation is most effective for nanocrystals with diameters between 4 and 16 nm.

Ethanol enrichment from ethanol-water mixtures using high frequency ultrasonic atomization.

The influence of high frequency ultrasound on the enrichment of ethanol from ethanol-water mixtures was investigated. Experiments performed in a continuous enrichment system showed that the generated atomized mist was at a higher ethanol concentration than the feed and the enrichment ratio was higher than the vapor liquid equilibrium curve for ethanol-water above 40 mol%. Well-controlled experiments were performed to analyze the effect of physical parameters; temperature, carrier gas flow and collection height on the enrichment. Droplet size measurements of the atomized mist and visualization of the oscillating fountain jet formed during sonication were made to understand the separation mechanism.

Influence of microwave heating on liquid-liquid phase inversion and temperature rates for immiscible mixtures.

Time dependencies of component temperatures for mixtures of immiscible liquids during microwave heating were studied for acetonitrile-cyclohexane and water-toluene. For the first time, we report microwave induced liquid-liquid phase inversion for acetonitrile-cyclohexane mixture: acetonitrile layer was initially at the bottom of the mixture, after 10 sec of microwave heating its density decreased and it inverted to the top of the mixture for the remainder of the microwave heating. This phase inversion could not be achieved by conventional radiant heating. The maximum rate of temperature growth for the polar component of the mixtures was 2 - 5 times larger than for the non-polar component. This suggests that microwave energy is absorbed by polar liquids (water or acetonitrile) and heat is transferred into the non-polar liquid (toluene or cyclohexane) in the mixture by conduction (in case of cyclohexane) or conduction and convection (in case of toluene). Comparison between experimental data and semi-empirical mathematical models, proposed in [Kennedy et at., 2009] showed good correlation. Average relative error between theoretical and experimental results did not exceed 7%. These results can be used to model the temperature kinetics of components for other multiphase mixtures.

NH4+-NH3 removal from simulated wastewater using UV-TiO2 photocatalysis: effect of co-pollutants and pH.

The main objective of the present study was to investigate the efficiency of titanium dioxide (TiO2) assisted photocatalytic degradation (PCD) process for the removal of ammonium-ammonia (NH4(+)-NH3) from the aqueous phase and in the presence of co-pollutants thiosulfate (S2O3(2-)) and p-cresol (C6H4CH3OH) under varying mixed conditions. For the NH4(+)-NH3 only PCD experiments, results showed higher NH4 -NH3 removal at pH 12 compared to pH 7 and 10. For the binary NH4(+)-NH3/S2O3(2-) studies the respective results indicated a significant lowering in NH4(+)-NH3 PCD in the presence of S2O32- at pH 7/12 whereas at pH 10 a marked increase in NH4(+)-NH3 removal transpired. A similar trend was noted for the p-cresol/NH4(+)-NH3 binary system. Comparing findings from the binary (NH4(+)-NH3/S2O3(2-) and p-cresol/NH4(+)-NH3) and tertiary (NH4(+)-NH3/S2O3(2-)/p-cresol) systems, at pH 10, showed fastest NH4(+)-NH3 removal transpiring for the tertiary system as compared to the binary systems, whereas both the binary systems indicated comparable NH4(+)-NH3 removal trends. The respective details have been discussed.

Transport coefficients in nonequilibrium gas-mixture flows with electronic excitation.

In the present paper, a one-temperature model of transport properties in chemically nonequilibrium neutral gas-mixture flows with electronic excitation is developed. The closed set of governing equations for the macroscopic parameters taking into account electronic degrees of freedom of both molecules and atoms is derived using the generalized Chapman-Enskog method. The transport algorithms for the calculation of the thermal-conductivity, diffusion, and viscosity coefficients are proposed. The developed theoretical model is applied for the calculation of the transport coefficients in the electronically excited N/N(2) mixture. The specific heats and transport coefficients are calculated in the temperature range 50-50,000 K. Two sets of data for the collision integrals are applied for the calculations. An important contribution of the excited electronic states to the heat transfer is shown. The Prandtl number of atomic species is found to be substantially nonconstant.

Assessment of three AC electroosmotic flow protocols for mixing in microfluidic channel.

This study performs an experimental investigation into the micromixer capabilities of three different protocols of AC electroosmotic flow (AC EOF), namely capacitive charging (CC), Faradaic charging (FC) and asymmetric polarization (AP). The results reveal that the vortices generated by the FC protocol (the frequency is around 50-350 Hz) are stronger than those induced by the CC protocol (the frequency is higher than 350 Hz), and therefore provide an improved mixing effect. However, in the FC protocol, the frequency of the external AC voltage must be carefully controlled to avoid damaging electrodes as a result of Faradaic reactions. The experimental results indicate that the AP polarization effect (the applied voltage and frequency are V(1) = 1 V(pp) and V(2) = 20 V(pp)/5 kHz) induces more powerful vortices than either the CC protocol or the FC protocol, and therefore yields a better mixing performance. Two AP-based micromixers are fabricated with symmetric and asymmetric electrode configurations, respectively. The mixing indices achieved by the two devices after an elapsed time of 60 seconds are found to be 56.49 % and 71.77 %, respectively. This result shows that of the two devices, an asymmetric electrode configuration represents a more suitable choice for micromixer in microfluidic devices.

Interactions of electrical fields with fluids: laboratory-on-a-chip applications.

The area of 'laboratory-on-a-chip', miniaturised or microfluidic analysis systems, is a rapidly developing field. At the microscale, electrokinetic processes become enhanced, and the advent of AC electrokinetics (EK) in recent years further promotes the development of electrokinetic devices for microfluidics. ACEK has demonstrated to manipulate fluids and polarisable particles at low voltages without some of the disadvantages from DCEK, such as electrochemical reactions and the limitation of low ionic strength fluids. The three major mechanisms of ACEK, that is, dielectrophoresis, AC electro-osmosis and AC electrothermal effect, provide versatility and flexibility to interface with many current methods and technologies in multiple biological, chemical and physical disciplines. This paper gives an overview of ACEK and its applications, with an emphasis on fluid manipulation by electric fields.

Droplet transport and coalescence kinetics in emulsions subjected to acoustic fields.

A method to aid the separation of the oil phase from aqueous emulsions using a low-intensity, resonant ultrasonic field has recently been developed. The density and compressibility difference between the dispersed and continuous phases within the emulsion results in a net force on the oil drops that pushes them toward the pressure antinodes of the standing-wave field, where coalescence subsequently occurs. A trajectory model is developed to predict the relative motion of drops subjected to the acoustic field. Such trajectories are sensitive to the physical properties and relative size of interacting drops, the initial configuration of the drops, and acoustic field parameters. Model predictions are validated by comparing experimentally observed trajectories with those predicted by the model. The modeling approach is then extended to determine the temporal evolution of the size of the region surrounding a target drop cleared by coalescence as a function of physical and acoustic field parameters. These results form the basis of a population balance model that attempts to track the size-evolution of a drop population coalescing under the influence of an acoustic field.

Experimental quantification of cavitation yield revisited: focus on high frequency ultrasound reactors.

Acoustic cavitation plays an important role in enhancing the reaction rate of chemical processes in sonochemical systems. However, quantification of cavitation intensity in sonochemical systems is generally limited to low frequency systems. In this study, an empirical determination of cavitation yield in high frequency ultrasound systems was performed by measuring the amount of iodine liberated from the oxidation of potassium iodide (KI) solution at 1.7 and 2.4 MHz. Experiments for determining cavitation were carried out at various solute (KI) concentrations under constant temperature, obtained by direct cooling of the solution and variable temperature conditions, in the absence of external cooling. Cavitation yield measurements, reported in this work, extend previously reported results and lend credence to the two step reaction pathway in high frequency systems. Additionally, the concentration of KI and temperature affect the cavitation yield of a system such that the iodine production is proportional to both conditions. It is proposed that direct cooling of sonicated KI solution may be advantageous for optimization of cavitation intensity in high frequency sonochemical reactors.

Effect of delay time and grid voltage changes on the average molecular mass of polydisperse polymers and polymeric blends determined by delayed extraction matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

The dependence of the calculated average molecular mass of a polyethylene glycol with a large polydispersity on the instrumental parameters adopted in the acquisition of mass spectra using delayed extraction matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (DE MALDI-TOFMS) was investigated. It has been shown that a combined effect of delay times and potential gradients can act on the ion cloud in the source chamber affecting both mass resolution and average molecular mass value of the analyzed polymeric sample. Also examined was a blend of two different polymers (a PEG and a PMMA commercial sample having a similar average molecular mass), which presents an additional problem concerning the discrimination among the different polymer species as a function of the experimental conditions. In this work, the best instrumental conditions to obtain both good resolution and a correct average molecular mass for the examined polydisperse sample are reported.

Oxidation of alkylarenes using aqueous potassium permanganate under cavitation: comparison of acoustic and hydrodynamic techniques.

Various alkylarenes were oxidized to the corresponding aryl carboxylic acids using aqueous potassium permanganate under heterogeneous condition in the presence of hydrodynamic cavitation and the results of the reaction have been compared with the acoustic cavitation in terms of their energy efficiency. The rate of reaction was determined for each reaction. In the oxidation of p-xylene, seven times more product could be obtained in the case of hydrodynamic cavitation than in the case of acoustic cavitation. The reaction was found to be considerably accelerated at ambient temperature.

A model for Joule heating-induced dispersion in microchip electrophoresis.

This paper presents an analytical and parameterized model for analyzing the effects of Joule heating on analyte dispersion in electrophoretic separation microchannels. We first obtain non-uniform temperature distributions in the channel resulting from Joule heating, and then determine variations in electrophoretic velocity, based on the fact that the analyte's electrophoretic mobility depends on the buffer viscosity and hence temperature. The convection-diffusion equation is then formulated and solved in terms of spatial moments of the analyte concentration. The resulting model is validated by both numerical simulations and experimental data, and holds for all mass transfer regimes, including unsteady dispersion processes that commonly occur in microchip electrophoresis. This model, which is given in terms of analytical expressions and fully parameterized with channel dimensions and material properties, applies to dispersion of analyte bands of general initial shape in straight and constant-radius-turn channels. As such, the model can be used to represent analyte dispersion in microchannels of more general shape, such as serpentine- or spiral-shaped channels.