Volunteer Computing Simulation Using Repast And Mason

Volunteer environments usually consist of a large number of computing nodes,with highly dynamic characteristics, therefore reliable models for a planning ofthe whole computing are highly desired. An easy to implement approach to mo-delling and simulation of such environments may employ agent-based universalsimulation frameworks, such as RePast or MASON. In the course of the paperthe above-mentioned simulation frameworks are adapted to support simulationof volunteer computing. After giving implementation details, selected resultsconcerning computing time and speedup are given and are compared with theones obtained from an actual volunteer environment

The 42nd Symposium Chromatographic Methods of Investigating Organic Compounds : Book of abstracts

The 42nd Symposium Chromatographic Methods of Investigating Organic Compounds : Book of abstracts. June 4-7, 2019, Szczyrk, Polan

Characterization of Phase I Hepatic Metabolites of Anti-Premature Ejaculation Drug Dapoxetine by UHPLC-ESI-Q-TOF

Determination of the metabolism pathway of xenobiotics undergoing the hepatic pass is a crucial aspect in drug development since the presence of toxic biotransformation products may result in significant side effects during the therapy. In this study, the complete hepatic metabolism pathway of dapoxetine established according to the human liver microsome assay with the use of a high-resolution LC–MS system was described. Eleven biotransformation products of dapoxetine, including eight metabolites not reported in the literature so far, were detected and identified. N-dealkylation, hydroxylation, N-oxidation and dearylation were found to be the main metabolic reactions for the investigated xenobiotic. In silico analysis of toxicity revealed that the reaction of didesmethylation may contribute to the increased carcinogenic potential of dapoxetine metabolites. On the other hand, N-oxidation and aromatic hydroxylation biotransformation reactions possibly lead to the formation of mutagenic compounds

Photocatalysis as a Tool for in Vitro Drug Metabolism Simulation: Multivariate Comparison of Twelve Metal Oxides on a Set of Twenty Model Drugs

The constant development in the area of medicinal substances on the market and their subsequent progress in the field of drug analysis has become one of the reasons for the search for alternative, cheaper, and faster methods to determine the metabolism pathways of new molecular entities (NMEs). The simulation of transformation processes using photocatalysis is considered to be one of the promising methods. Although its effectiveness has been proven, the research has so far focused especially on titanium dioxide, while a more accurate comparison of the suitability of different photocatalysts in terms of their use in drug metabolism studies has not been performed. For this purpose, a set of twelve metal oxides was prepared and their photocatalytic efficiency in the direction of drug metabolism mimicking was checked on a model mixture of twenty medicinal substances differing both in chemical structure and pharmacological properties. Incubation with human liver microsomes (HLMs) was used as the reference method. The metabolic profiles obtained with the use of LC-MS analysis were compared using multidimensional chemometric techniques; and the graphic presentation of the results in the form of PCA plot and cluster dendrogram enabled their detailed interpretation and discussion. All tested photocatalysts confirmed their effectiveness. However, the exact outcome of the study indicate advantage of the WO3-assisted photocatalysis over other metal oxides

Identification of the New Metabolite of Nebivolol Using Liquid Chromatography Coupled with High-Resolution Mass Spectrometry and Chemometrics

In this study, the phase I hepatic metabolism pathway of a cardiovascular drug nebivolol was proposed on the basis of a human liver microsomes assay with the use of LC-HR-MS coupled with the chemometric method. Six biotransformation products were found with the assistance of chemometric analysis. Five of them were identified as the previously reported products of alicyclic hydroxylation and dihydroxylation, aromatic hydroxylation, as well as alicyclic oxidation of the parent compound. Moreover, one metabolite, not reported so far, was found to be a product of N-dealkylation of nebivolol—2-amino-1-(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-yl)ethan-1-ol. The novel metabolite was submitted to an in silico toxicity analysis to assess its biological properties. The applied computational methods indicated a significantly elevated risk of its mutagenic activity, compared to the parent molecule. Several metabolites of the nebivolol described in the literature were not detected in this study, indicating their non-hepatic origin

Brain-derived neurotropic factor, vascular endothelial growth factor and matrix metalloproteinases as markers of metabolic status in non-growth hormone-treated girls with Turner syndrome

BackgroundTurner syndrome (TS) presents a high risk of congenital heart defects and may predispose to both obesity and related metabolic complications. Hence the search for new markers as potential early predictors of the metabolic syndrome (MetS) and cardiovascular diseases appears warranted.ObjectiveTo assess MMP-1 (matrix metalloproteinase-1), MMP-2 (matrix metalloproteinase-2), MMP-9 (matrix metallopeptidase-9), BDNF (brain-derived neurotrophic factor), GDNF (glial cell line-derived neurotrophic factor), and VEGF (vascular endothelial growth factor) in non-MetS TS girls not treated with growth hormone (GH) vs. healthy short stature girls, and to assess the connection with basic metabolic parameters.MethodThe concentrations of circulating MMP-1, MMP-2, MMP-9, BDNF, GDNF and VEGF were measured in 12 patients with TS not treated with growth hormone. The control group was composed of 17 girls with non-pathologic short stature. The patients’ clinical and biochemical phenotypes were determined by weight, height, total cholesterol, HDL cholesterol, triglycerides, glucose, aminotransferases, IGF1, TSH and fT4.ResultsThere were no differences in mean age, weight, BMI Z-Score, or hSDS between the studied group and the controls; however, they differed in baseline values of ALT (18.2 ± 4.2 vs. 14.2 ± 4.1, p= 0.02), BDNF [29951.5 (26176.9 – 41271.9) vs. 23131.7 (18392.4 – 28313.3), p=0.01] and MMP-2 [91.8 (71.7 – 111.0) vs. 143.6 (123.7 - 244.5), p< 0.001]. BDNF correlated with ALT activity (r = 0.56 p = 0.002) and BMI Z-score (r = 0.38 p = 0.042), while MMP-2 correlated with HDL concentration (r = 0.48 p = 0.029) in all the patients. The analysis of the study group alone revealed significant positive correlations between MMP-9 and TSH (r = 0.74 p = 0.036), BDNF and both ALT (r = 0.73 p = 0.038) and TSH (r = 0.85 p = 0.008), and a negative correlation between MMP-1 and fT4 (r = -0.75 p = 0.032). The control group did not present any significant correlations.ConclusionThe higher concentrations of BDNF and lower of MMP-2 found in girls with TS without MetS compared to healthy girls with short stature, could have a major impact on the future “natural” development of the metabolic status. Our findings need further studies

Assessment of Cultivated Soil Contamination by Potentially Toxic Metals as a Result of a Galvanizing Plant Failure

Zinc is one of the more mobile metals in the soil and thus involves the risk of entering the food chain. Zinc compounds are used in the galvanization process, which is assumed to be safe for the environment. However, random events or failures such as unsealing bathtubs with liquid zinc or hydrochloric acid, as well as violent fires in industrial halls, may pose a real threat to the environment, including human health. Therefore, this research was carried out to determine the content of zinc and selected potentially toxic metals in arable soils after a failure in a galvanizing plant located in the village of Dębska Wola (southeastern Poland). In addition, the potential risk associated with excessive accumulation of identified pollutants in the environment was assessed. In order to determine the level of contamination, soil samples were taken, and basic physical and chemical properties were analysed. The concentrations of Zn, Pb, and Cd in the soil were determined using the atomic emission spectrometry technique with inductively coupled plasma (ICP-OES), and pH measurements were performed using the potentiometric method after prior wet mineralisation of the research samples. The analysed samples had a varied pH of the organic–mineral horizon from pHH2O 4.66 to pHH2O 5.33 and from pHKCl 3.89 to pHKCl 5.06. As a result of a failure, toxic metal fumes were released into the atmosphere, causing concentrations of Zn in the soil samples from 0–5 cm in the range of 1201–2007 mg∙kg−1, as well as Pb (109–509 mg∙kg−1) and Cd (4.6–17 mg∙kg−1). High contents of zinc and lead found in several soil samples are of anthropogenic nature and require detailed monitoring in order to eliminate the risk associated with their accumulation. The study area should be re-analysed to determine the rate of reclamation of degraded soils

Leaves of White Beetroot As a New Source of Antioxidant and Anti-Inflammatory Compounds

The white beetroot cv. Śnieżna Kula is the first betanin-free beetroot registered in the European Union. The aim of this study was to compare the phenolic acids profile and antioxidant capacity of leaves of white (SK) and red (CC) beetroots and red (LC) and white (BL) Swiss chard growing in Poland. LC leaves were the richest source of total phenolics (16.55 mg GAE/g FW) and phenolic acids (1.81 mg/g FW), while the highest content of flavonoids was determined in CC leaves (1.6 mg QE/g FW). The highest antiradical activity was observed for LC, whereas CC extract exhibited the highest chelating power. BL and CC leaf extracts demonstrated high LOX inhibitory potential (EC50 = 53.23 and 56.97 mg FW/mL, respectively). An uncompetitive type of LOX inhibition was obtained for all extracts. SK extracts demonstrated the highest XO inhibitory activity (EC50 = 81.04 mg FW/mL). A noncompetitive type of XO inhibition was obtained in both extracts from red leaves (CC and LC), whereas an uncompetitive mode of inhibition was observed in the case of white leaf (SK and LC) extracts. Thus, it can be assumed that the presence of betanin influences the XO inhibition mechanism