Stochastic Order and Generalized Weighted Mean Invariance

In this paper, we present order invariance theoretical results for weighted quasi-arithmetic means of a monotonic series of numbers. The quasi-arithmetic mean, or Kolmogorov–Nagumo mean, generalizes the classical mean and appears in many disciplines, from information theory to physics, from economics to traffic flow. Stochastic orders are defined on weights (or equivalently, discrete probability distributions). They were introduced to study risk in economics and decision theory, and recently have found utility in Monte Carlo techniques and in image processing. We show in this paper that, if two distributions of weights are ordered under first stochastic order, then for any monotonic series of numbers their weighted quasi-arithmetic means share the same order. This means for instance that arithmetic and harmonic mean for two different distributions of weights always have to be aligned if the weights are stochastically ordered, this is, either both means increase or both decrease. We explore the invariance properties when convex (concave) functions define both the quasi-arithmetic mean and the series of numbers, we show its relationship with increasing concave order and increasing convex order, and we observe the important role played by a new defined mirror property of stochastic orders. We also give some applications to entropy and cross-entropy and present an example of multiple importance sampling Monte Carlo technique that illustrates the usefulness and transversality of our approach. Invariance theorems are useful when a system is represented by a set of quasi-arithmetic means and we want to change the distribution of weights so that all means evolve in the same direction.     

Simultaneous determination of sulfoxaflor and its metabolites,X11719474 and X11721061, in brown rice and rice straw after field application using LC-MS/MS

The present study was carried out to develop an analytical method for simultaneously detecting and quantifying sulfoxaflor and its metabolites (X11721061, X11719474) in brown rice and rice straw using liquid chromatography–tandem mass spectrometry. The parent compound and its metabolites were extracted and purified using original ‘QuEChERS’ method with modification. The matrix-matched calibration curve of sulfoxaflor and its metabolites in both matrices achieved good linearity with determination coefficients (R²) ≥0.9944. The overall recoveries of sulfoxaflor at two fortification levels (rice: 0.2 and 1.0 mg/kg; rice straw: 0.4 and 2.0 mg/kg) ranged from 97.37% to 107.71% with relative standard deviations (RSDs) <5%. On the other hand, the recoveries of both metabolites (X11721061 and X11719474) at 0.1 and 0.5 mg/kg (rice) and 0.2 and 1.0 mg/kg (rice straw) were satisfactory with values ranging from 83.70 % to 112.60% with RSDs <8%. During storage at ?20°C, the analyte and its metabolites were stable for up to 87 days. The limits of quantification of 0.02 mg/kg were lower than the maximum residue limit (0.2 mg/kg) set by the Korean Ministry of Food and Drug Safety for brown rice. The method was successfully applied to paddy field treated with different programme schedules and a preharvest interval of 7 days was proposed based upon the current study. In sum, the developed method is accurate and reproducible for ensuring the reliable determination of sulfoxaflor (and its metabolites) in harvested rice grain and straw samples from the field. The residual level of parent compound does not seem to pose any hazardous effect and treated rice could be safely used for consumption.     

Down-regulation of Bcl-2 and Akt induced by combination of photoactivated hypericin and genistein in human breast cancer cells

Presented experiment considers combination of genistein and photodynamic therapy with hypericin with a view to achieve higher therapeutic outcome in human breast adenocarcinoma cell lines MCF-7 and MDA-MB-231, both identified in our conditions as photodynamic therapy resistant. Since genistein is known to suppress Bcl-2 expression, we predicted that photodynamic therapy with hypericin might benefit from mutual therapeutic combination. In line with our expectations, combined treatment led to down-regulation of Bcl-2 and up-regulation of Bax in both cell lines as well as to suppression of Akt and Erk1/2 phosphorylation induced by photoactivated hypericin in MCF-7 cells. Although Akt and Erk1/2 phosphorylation was not stimulated by photodynamic therapy with hypericin in MDA-MB-231 cells, it was effectively suppressed in combination. Variations in cell death signaling favoring apoptosis were indeed accompanied by cell cycle arrest in G₂/M-phase, activation of caspase-7, PARP cleavage and increased occurrence of cells with apoptotic morphology of nucleus. All these events corresponded with suppression of proliferation and significantly lowered clonogenic ability of treated cells. In conclusion, our results indicate that pre-treatment with tyrosine kinase inhibitor genistein may significantly improve the effectiveness of photodynamic therapy with hypericin in MCF-7 and MDA-MB-231 breast cancer cells.     

Adenine versus guanine quartets in aqueous solution: dispersion-corrected DFT study on the differences in π-stacking and hydrogen-bonding behavior

We have investigated the performance of the dispersion-corrected density functionals (BLYP-D, BP86-D and PBE-D) and the widely used B3LYP functional for describing the hydrogen bonds and the stacking interactions in DNA base dimers. For the gas-phase situation, the bonding energies have been compared to the best ab initio results available in the literature. All dispersion-corrected functionals reproduce well the ab initio results, whereas B3LYP fails completely for the stacked systems. The use of the proper functional leads us to find minima for the adenine quartets, which are energetically and structurally very different from the C_4h structures, and might explain why adenine has to be sandwiched between guanine quartets to form planar adenine quartets.     

Molecular mechanism of acid-triggered aryl-halide reductive elimination in well-defined aryl-Cu(III)-halide species

Well-defined aryl-Cu(III)-halide species undergo reductive elimination upon acid addition resulting in the formation of strong aryl-halide bonds. The computationally studied mechanism points towards ligand protonation as the rate-determining step, in agreement with previous experimental data.     

Uptake and biological responses to nano-Fe versus soluble FeCl3 in excised mussel gills

Nano-Fe particle uptake was experimentally examined in vitro using excised gills and blood cells of the edible blue mussel Mytilus sp. Whole gills were exposed to both Fe₂O₃ nanoparticles and a solution of the hydrated FeCl₃ salt, for up to 12 h, and blood cells for 30 min. Equimolar Fe⁺³ in the nano- and the soluble form was estimated under the assumption of dense spherical particles accommodating the same number of Fe⁺³ as in the dissolved salt solution, namely: 1,000 μg L⁻¹ Fe₂O₃ equivalent to 100 μg L⁻¹ FeCl₃·6H₂O. Putative toxic impact of nano-Fe in gill epithelia and blood cells was assessed by an array of techniques including light- and electron microscopy, biomarkers for oxidative stress (lipid peroxidation levels), neurotoxic effects (acetylcholinesterase activity) and cytotoxicity (neutral red retention). Total and filtered fractions (20 and 200 nm, respectively) of Fe were analysed by ICP-OES. Our results provide evidence for the following: (1) much of both the soluble (95%) and the nano-Fe (90%) were removed from the water column within 12 h; (2) dissolved- and nano-Fe seemed to follow different routes of uptake within the gill epithelium; (3) both nano-Fe and soluble FeCl₃ caused similar impairment of lysosomal stability in circulating blood cells; (4) lipid peroxidation in gills exposed to the two distinct forms of Fe was increased, while acetylcholinesterase activity was unaffected. In these short-term in vitro studies, there appears to be little difference in toxic response between exposure to the Fe salt and the nano-Fe indicating that, in this case, the nanoparticles do not invoke special properties affecting biological function in gills. However, with the use of nano-Fe as a food additive, clearly longer-term in vivo studies are warranted.     

Testosterone metabolism revisited: discovery of new metabolites

The metabolism of testosterone is revisited. Four previously unreported metabolites were detected in urine after hydrolysis with KOH using a liquid chromatography–tandem mass spectrometry method and precursor ion scan mode. The metabolites were characterized by a product ion scan obtained with accurate mass measurements. Androsta-4,6-dien-3,17-dione, androsta-1,4-dien-3,17-dione, 17-hydroxy-androsta-4,6-dien-3-one and 15-androsten-3,17-dione were proposed as feasible structures for these metabolites on the basis of the mass spectrometry data. The proposed structures were confirmed by analysis of synthetic reference compounds. Only 15-androsten-3,17-dione could not be confirmed, owing to the lack of a commercially available standard. That all four compounds are testosterone metabolites was confirmed by the qualitative analysis of several urine samples collected before and after administration of testosterone undecanoate. The metabolite androsta-1,4-dien-3,17-dione has a structure analogous to that of the exogenous anabolic steroid boldenone. Specific transitions for boldenone and its metabolite 17β-hydroxy-5β-androst-1-en-3-one were also monitored. Both compounds were also detected after KOH treatment, suggesting that this metabolic pathway is involved in the endogenous detection of boldenone previously reported by several authors.     

Effects on feeding rate and biomarker responses of marine mussels experimentally exposed to propranolol and acetaminophen

Environmental risk assessments of human pharmaceuticals and other ‘emerging contaminants’ should integrate both population-relevant endpoints and biomarkers of potential modes of action in a range of species. Adult Mytilus galloprovincialis were exposed to the beta-adrenergic receptor blocker propranolol or to the anti-inflammatory drug acetaminophen (paracetamol), both commonly used therapeutic drugs present in aquatic ecosystems. Mussels were exposed under semi-static conditions for 10 days to either acetaminophen (CAS number 103-90-2; mean measured concentrations 23 and 403 μg/L) or propranolol hydrochloride (CAS number 318-98-9; mean measured propranolol concentrations 11 and 147 μg/L) at 15 ± 1 °C sea water. Feeding rate was assessed as an indicator of general toxicity. For propranolol, the 10-day no-observed effect concentration (^{feeding rate}NOEC) and lowest observed effect concentration (^{feeding rate}LOEC) were 11 and 147 μg/L, respectively. For acetaminophen, feeding rate was increased at both 23 and 403 μg/L, suggesting a 10-day ^{feeding rate}NOEC of 403 μg/L. Primarily, phase I carboxylesterase (CbE), phase II glutathione S-transferase (GST) and the anti-oxidant catalase activities were evaluated in digestive gland. Gill GST and acetylcholinesterase (AChE) activities were also measured. Lipid peroxidation (LPO) levels were measured in both tissues to assess oxidative stress. Some enzymatic activities in liver were also reduced after propranolol exposure whilst acetaminophen enhanced them (CbE p < 0.05). Acetaminophen exposure significantly increased hepatic LPO levels and inhibited AChE activity in gill (10-day NOEC and LOEC of 23 and 403 μg/L, respectively), whereas propranolol (11 μg/L) enhanced gill GST.     

Theoretical studies on aromaticity of selected hydroxypyrones. Part 3#. Chelatoaromaticity phenomenon in metalcomplexes of hydroxypyrones

The aim of this project is to study the aromatic properties of various forms (neutral, cationic, and anionic) of selected hydroxypyrones (pyromeconic acid, maltol, and ethylmaltol) and their metalcomplexes with aluminum, gallium, and indium ions. Aromaticity of hydroxypyrone metalcomplexes is important because it can influence the stability of such complexes, which is crucial for their applications in medicinal and environmental chemistry. Results from ten different indices of aromaticity (HOMA, NICS(0), NICS(1), NICS_scan, ASE_iso, PDI, FLU, I_ring, MCI, and KMCI) show that aromaticity in hydroxypyrones decreases in the order cations > neutral molecules > anions. Performed calculations situate the aromaticities of ligands in metalcomplexes close to their respective cations. This means that complexation causes a significant increase of the aromaticity of ligands, which stabilizes formed chelatocomplexes. On the other hand, we clearly show that rings that are involved in binding metal ions are not aromatic. Copyright © 2010 John Wiley & Sons, Ltd.