Cyclamate intake and cyclohexylamine excretion are not related to male fertility in humans

Cyclamate and its metabolite cyclohexylamine affect male fertility in high dose animal studies, but this affect has not been investigated in epidemiological studies. This paper reports the first epidemiological study designed to investigate the possibility of a relationship between cyclamate and cyclohexylamine and male fertility in humans, in which 405 cases of clinically defined infertility in men and 379 controls were surveyed. Semen evaluation, urine analysis for cyclamate and cyclohexylamine and dietary questionnaires were compared between cases and controls. No evidence was found of a significant association between cyclamate intake and male infertility; neither high cyclamate nor high cyclohexylamine excretion were associated with elevated risk. The lack of association remained after adjusting by age, area of residence, education, total energy intake and other variables. No significant correlations were observed between cyclamate intake, metabolism or excretion, and sperm count and motility. The results demonstrate no effect of cyclamate or cyclohexylamine on male fertility at the present levels of cyclamate consumption.     

Relative involvement of protein kinase C and of the estrogen receptor in the cytotoxic action of a population of triphenylethylenes on MCF7 cells as revealed by correspondence factorial (CF) analysis

A multivariate statistical method, correspondence factorial (CF) analysis, was used to examine the correlations among the protein binding and cell proliferation effects of a series of 36 di- and triphenylethylenes (DPEs and TPEs). The analysis was applied to a study which measured their competition for estradiol binding to cytosol estrogen receptor (ER), their influence on protein kinase C (PKC) activity under different conditions of enzyme activation, their ability to promote the growth of a breast cancer cell line and to inhibit growth at high concentrations (cytotoxicity). The CF analysis revealed several levels of correlation. First, it distinguished those molecules within the population that stimulated rather than inhibited PKC activity. Second, it made apparent a strong correlation between cytotoxicity and inhibition of Ca++ and phosphatidylserine-dependent PKC activity, which was most marked when the enzyme had been activated by diacylglycerol indicating that PKC inhibition under physiological conditions might contribute to the overall cytotoxicity of these compounds. Third, a lower level of correlation was established between competition for ER binding and cytotoxicity. Taken together, the results suggest that MCF7 cells might be most sensitive to a cytotoxic effect of TPEs (via PKC and other targets) when they at the same time decrease estrogen-stimulated proliferation via an ER-mediated antiestrogenic effect.     

Harmonization of renewable electricity feed-in laws in the European Union

This paper focuses on the harmonization of feed-in laws in the European Union as a support mechanism for the promotion of renewable electricity. In particular, it proposes a methodology for harmonization based on a feed-in law with a modular and transparent premium for renewable electricity producers. This premium considers technology costs, some grid services, political incentives and national priorities. The proposed approach includes flexibility mechanisms to update and revise premiums, to avoid windfall profits for producers, and to share technology innovation benefits with electricity consumers while maintaining incentives for innovation. Our approach is based on the review of the main features of the German and Spanish feed-in laws, and takes into account other necessary considerations for harmonization, such as grid access, funding, definitions and standards, ownership of rights derived from renewables, and exceptions for small non-commercial producers and energy-intensive industries.     

Validation of a Gas Chromatography-Mass Spectrometry Method for the Measurement of the Redox State Metabolic Ratios Lactate/Pyruvate and β-Hydroxybutyrate/Acetoacetate in Biological Samples

The metabolic ratios lactate/pyruvate and β-hydroxybutyrate/acetoacetate are considered valuable tools to evaluate the in vivo redox cellular state by estimating the free NAD+/NADH in cytoplasm and mitochondria, respectively. The aim of the current study was to validate a gas-chromatography mass spectrometry method for simultaneous determination of the four metabolites in plasma and liver tissue. The procedure included an o-phenylenediamine microwave-assisted derivatization, followed by liquid-liquid extraction with ethyl acetate and silylation with bis(trimethylsilyl)trifluoroacetamide:trimethylchlorosilane 99:1. The calibration curves presented acceptable linearity, with a limit of quantification of 0.001 mM for pyruvate, β-hydroxybutyrate and acetoacetate and of 0.01 mM for lactate. The intra-day and inter-day accuracy and precision were within the European Medicines Agency’s Guideline specifications. No significant differences were observed in the slope coefficient of three-point standard metabolite-spiked curves in plasma or liver and water, and acceptable recoveries were obtained in the metabolite-spiked samples. Applicability of the method was tested in precision-cut liver rat slices and also in HepG2 cells incubated under different experimental conditions challenging the redox state. In conclusion, the validated method presented good sensitivity, specificity and reproducibility in the quantification of lactate/pyruvate and β-hydroxybutyrate/acetate metabolites and may be useful in the evaluation of in vivo redox states.     

A Methionine Chemical Shift Based Order Parameter Characterizing Global Protein Dynamics

Coupling of side chain dynamics over long distances is an important component of allostery. Methionine side chains show the largest intrinsic flexibility among methyl-containing residues but the actual degree of conformational averaging depends on the proximity and mobility of neighboring residues. The ¹³C NMR chemical shifts of the methyl groups of methionine residues located at long distances in the same protein show a similar scaling with respect to the values predicted from the static X-ray structure by quantum methods. This results in a good linear correlation between calculated and observed chemical shifts. The slope is protein dependent and ranges from zero for the highly flexible calmodulin to 0.7 for the much more rigid calcineurin catalytic domain. The linear correlation is indicative of a similar level of side-chain conformational averaging over long distances, and the slope of the correlation line can be interpreted as an order parameter of the global side-chain flexibility.     

Effects of allelochemicals on plant respiration and oxygen isotope fractionation by the alternative oxidase

The goal of this investigation was to determine the effects of allelochemicals on plant respiration that thereby may be responsible for their role in growth inhibition. We have tested the effects of juglone, quercetin, cinnamic acid, and-pinene on respiration rates, and electron partitioning through the cytochrome and alternative respiratory pathways, by measuring on-line oxygen consumption and oxygen isotope fractionation in soybean cotyledon tissue. Cinnamic acid and-pinene decreased the oxygen consumption rate and increased the relative partitioning of electron transport to the alternative pathway. Possible biochemical mechanisms of these effects are discussed.     

Discovering social structures of local influence by using tweetStimuli

Information diffusion in large-scale networks has been studied to identify the users influence. The influence has been targeted as a key feature either to reach large populations or influencing public opinion. Through the use of micro-blogs, such as Twitter, global influencers have been identified and ranked based on message propagation (retweets). In this paper, a new application is presented, which allows to find first and classify then the local influence on Twitter: who have influenced you and who have been influenced by you. Until now, social structures of tweets’ original authors that have been either retweeted or marked as favourites are unobservable. Throughout this application, these structures can be discovered and they reveal the existence of communities formed by users of similar profile (that are connected among them) interrelated with other similar profile users’ communities.     

Solving weighted CSPs with meta-constraints by reformulation into satisfiability modulo theories

We introduce WSimply, a new framework for modelling and solving Weighted Constraint Satisfaction Problems (WCSP) using Satisfiability Modulo Theories (SMT) technology. In contrast to other well-known approaches designed for extensional representation of goods or no-goods, and with few declarative facilities, our approach aims to follow an intensional and declarative syntax style. In addition, our language has built-in support for some meta-constraints, such as priority and homogeneity, which allows the user to easily specify rich requirements on the desired solutions, such as preferences and fairness. We propose two alternative strategies for solving these WCSP instances using SMT. The first is the reformulation into Weighted SMT (WSMT) and the application of satisfiability test based algorithms from recent contributions in the Weighted Maximum Satisfiability field. The second one is the reformulation into an operation research-like style which involves an optimisation variable or objective function and the application of optimisation SMT solvers. We present experimental results of two well-known problems: the Nurse Rostering Problem (NRP) and a variant of the Balanced Academic Curriculum Problem (BACP), and provide some insights into the impact of the addition of meta-constraints on the quality of the solutions and the solving time.