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AbstractPolymorphisms in the genes of drug-metabolizing enzymes have the potential to contribute to inter-individual differences in drug pharmacokinetics and toxicity. A custom next-generation sequencing (NGS) panel was used in 71 kidney transplanted patients to study the polymorphisms of 11 genes relevant to the metabolism of immunosuppressive drugs. Cyclosporine A and tacrolimus concentrations were determined by a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. More than 1000 polymorphisms were found in the studied 11 genes, and 45% of them were different non-synonymous variants. Eleven missense mutations were observed in the CYP3A7 gene, resulting in increased metabolism of tacrolimus at day 21 post-transplantation (6.7 µg/L vs. 10.3 µg/L; p = 0.048). Two alleles encoding a cytochrome P450 2D6 enzyme with impaired function—CYP2D6*4(non-functional) and CYP2D6*10(decreased function), were found in the studied group and both of them were associated with higher levels of tacrolimus at day 14 (10.1 µg/L; p = 0.021 and 9.7 µg/L; p = 0.036, vs. 7.7 µg/L respectively). Altered function of ABC transporters C3 and C2 was also associated with increased TAC concentration. ABCC3 significantly influenced TAC metabolism by itself, but polymorphisms affecting both ABCC3 and ABCC2 resulted in higher changes: 13.6 µg/L vs. 7.9 µg/L, day 14 (p = 0.003) and 20 µg/L versus 9.3 µg/L, day 21 (p = 0.019). All associations were also checked for variants affecting the activity of CYP3A4 and CYP3A5. Despite its small size, the study points out that the pharmacogenetics of calcineurin inhibitors may also be influenced by other genes besides CYP3A4 and CYP3A5.

The paper presents multifactor experimental studies for determining the apparent soil resistivity and the dielectric permittivity depending on the frequency of the electromagnetic field, the multilayered structure, moisture content and density of the soil. The gravimetric method for considering the soil moisture during the experimental researches was chosen. The received experimental results were statistically processed and a mathematical modelling of the controlled parameters was performed considering the specifics of the examined soil. These analytically obtained results of the dependences would contribute to more precise sizing of the grounding systems and could be used for creation of accurate simulation models for the study of wave processes in them.

In this article, I argue that Poincaré’s acceptance of the atom does not indicate a shift from instrumentalism to scientific realism. I examine the implications of Poincaré’s acceptance of the existence of the atom for our current understanding of his philosophy of science. Specifically, how can we understand Poincaré’s acceptance of the atom in structural realist terms? From a careful examination of his 1912 paper, I suggest that it does not entail scientific realism in the sense of acceptance of the fundamental existence of atoms but, rather, argues against fundamental entities. I argue that Poincaré’s paper motivates a nonfundamentalist view about the world and that this is compatible with his structuralism.

SIGMOD has offered, since 2008, to verify the experiments published in the papers accepted at the conference. This year, we have been in charge of reproducing the experiments provided by the authors (repeatability), and exploring changes to experiment parameters (workability). In this paper, we assess the SIGMOD repeatability process in terms of participation, review process and results. While the participation is stable in terms of number of submissions, we find this year a sharp contrast between the high participation from Asian authors and the low participation from American authors. We also find that most experiments are distributed as Linux packages accompanied by instructions on how to setup and run the experiments. We are still far from the vision of executable papers.

The four possible diastereoisomers of 4,5-diphenylcyclophosphamides (2-5) and their N-methyl analogues (6-9) have been synthesized via condensation of aminopropanols 10 and 11 (threo- and erythro) with bis-(2-chloroethyl)-phosphoramidic dichloride 12. Anticancer screening tests against L 1210 lymphoid leukaemia in mice did not show any therapeutic activity.

Food irradiation technologies are used to reduce the risk of food borne diseases by eliminating pathogenic microorganisms, prolonging shelf life and reducing storage losses by delaying ripening, germination or sprouting. However, application of irradiation in food technology can negatively influence the biologically active compounds in foods. In this research, the effect of gamma-irradiation on the antioxidant activity of Bulgarian teas was investigated. The aim of the study was to evaluate the total phenolic and tannin content and antioxidant activity of ethanolic extracts of Bulgarian herbal teas before and after gamma-irradiation. Mursalski tea (Sideritis scardica), Mashterka tea (Thymus serpyllum), Good Night tea (tea mix), Staroplaninski tea (Balkan tea mix), Trakia tea (tea mix), and Mountain tea (Planinski tea mix) were selected for this study. Gamma-irradiation was applied at the absorbed dose of 5 kGy. Antioxidant activity of non-irradiated and irradiated teas was determined by measuring antiradical activity against DPPH•and ABTS•+and the ability to reduce ferrous ions. The highest total phenolic content was found in Mursalski tea (268 mg/g), and the highest tannin content in Good Night tea (168 mg/g). FRAP, TEAC and DPPH assays revealed that the most active samples were Staroplaninski (2.78 mmol Fe (II)/g), Planinski (0.87 mmol Trolox/g) and Planinski (0.032 mg/mL), respectively. The radical scavenging activity of irradiated tea samples was maintained after gamma-irradiation. The most interesting extract from irradiated tea studied was Staroplaninski, which demonstrated a higher antioxidant potential in the irradiated sample compared with the non-irradiated sample.