Anti-Inflammatory Activity of Soluble Epoxide Hydrolase Inhibitors Based on Selenoureas Bearing an Adamantane Moiety

The inhibitory potency of the series of inhibitors of the soluble epoxide hydrolase (sEH) based on the selenourea moiety and containing adamantane and aromatic lipophilic groups ranges from 34.3 nM to 1.2 μM. The most active compound 5d possesses aliphatic spacers between the selenourea group and lipophilic fragments. Synthesized compounds were tested against the LPS-induced activation of primary murine macrophages. The most prominent anti-inflammatory activity, defined as a suppression of nitric oxide synthesis by LPS-stimulated macrophages, was demonstrated for compounds 4a and 5b. The cytotoxicity of the obtained substances was studied using human neuroblastoma and fibroblast cell cultures. Using these cell assays, the cytotoxic concentration for 4a was 4.7–18.4 times higher than the effective anti-inflammatory concentration. The genotoxicity and the ability to induce oxidative stress was studied using bacterial lux-biosensors. Substance 4a does not exhibit genotoxic properties, but it can cause oxidative stress at concentrations above 50 µM. Put together, the data showed the efficacy and safety of compound 4a.     

Back and forth between continuous and discrete for the working computer scientist

This paper gives a perfect, ideal, discretization of continuous notions. This is a very convenient frame to treat continuous problems or theories with the help of a computer. This is illustrated by the conversion of algorithms using real numbers into algorithms using integers only and the founding of discrete geometry.     

Unraveling Membrane Perturbations Caused by the Bacterial Riboregulator Hfq

Hfq is a pleiotropic regulator that mediates several aspects of bacterial RNA metabolism. The protein notably regulates translation efficiency and RNA decay in Gram-negative bacteria, usually via its interaction with small regulatory RNAs. Previously, we showed that the Hfq C-terminal region forms an amyloid-like structure and that these fibrils interact with membranes. The immediate consequence of this interaction is a disruption of the membrane, but the effect on Hfq structure was unknown. To investigate details of the mechanism of interaction, the present work uses different in vitro biophysical approaches. We show that the Hfq C-terminal region influences membrane integrity and, conversely, that the membrane specifically affects the amyloid assembly. The reported effect of this bacterial master regulator on membrane integrity is discussed in light of the possible consequence on small regulatory RNA-based regulation.     

Next-Generation Grade and Survival Expression Biomarkers of Human Gliomas Based on Algorithmically Reconstructed Molecular Pathways

In gliomas, expression of certain marker genes is strongly associated with survival and tumor type and often exceeds histological assessments. Using a human interactome model, we algorithmically reconstructed 7494 new-type molecular pathways that are centered each on an individual protein. Each single-gene expression and gene-centric pathway activation was tested as a survival and tumor grade biomarker in gliomas and their diagnostic subgroups (IDH mutant or wild type, IDH mutant with 1p/19q co-deletion, MGMT promoter methylated or unmethylated), including the three major molecular subtypes of glioblastoma (proneural, mesenchymal, classical). We used three datasets from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas, which in total include 527 glioblastoma and 1097 low grade glioma profiles. We identified 2724 such gene and 2418 pathway survival biomarkers out of total 17,717 genes and 7494 pathways analyzed. We then assessed tumor grade and molecular subtype biomarkers and with the threshold of AUC > 0.7 identified 1322/982 gene biomarkers and 472/537 pathway biomarkers. This suggests roughly two times greater efficacy of the reconstructed pathway approach compared to gene biomarkers. Thus, we conclude that activation levels of algorithmically reconstructed gene-centric pathways are a potent class of new-generation diagnostic and prognostic biomarkers for gliomas.     

Molecular characterization of Escherichia coli O157 contamination routes in a cattle slaughterhouse

In a cattle slaughterhouse, sampling was performed over a 1-week period to examine the prevalence and possible contamination routes of Escherichia coli O157. Each sampling day, swab samples were collected from the slaughterhouse environment before onset of slaughter, from the slaughterline, and from 20 successively slaughtered animals. Isolation of E. coli O157 consisted of a 6-hour enrichment followed by immunomagnetic separation and selective plating. From the 394 samples taken, 84 (21%) were positive for E. coli O157. Pulsed-field gel electrophoresis (PFGE) of collected isolates produced 26 different profiles, from which 5 PFGE profiles carried two or more Stx genes. The combination of PFGE profiles and Stx types resulted in 32 different E. coli O157 types. E. coli O157 was found in the slaughterhouse environment before the onset of slaughter. The first two sampling days, feces and carcasses were found negative. On the third sampling day, five fecal samples and four carcasses from animals negative in the feces were positive. Hide of the anal region and the shoulder were found positive every sampling day. The shoulder hide was more than twice as contaminated as the anal region hide. Typing of different isolates from a sample showed that frequently different E. coli O157 types were presented. On sampling days 1 and 2, types present in the environment and on the hides of the slaughtered animals differed. On the third sampling day, two dominant types were found in the environment (even before the onset of slaughter), as well as on the hides, feces, and carcasses. Although examined animals originated from different farms, one (two on day 3) dominant E. coli O157 type was present on their hides each sampling day. These data indicated that (i) the progress of contamination can differ from day to day within a slaughterhouse and (ii) contact between animals after the departure from the farm can have a large effect on the spread of E. coli O157 hide contamination.     

Twelve-Nitrogen-Atom Cyclic Structure Stabilized by 3d-Element Atoms: Quantum Chemical Modeling

Using various versions of density functional theory (DFT), DFT M06/TZVP, DFT B3PW91/TZVP, DFT OPBE/TZVP, and, partially, the MP2 method, the possibility of the existence of 3d-element (M) compounds with nitrogen having unusual M: nitrogen ratio 1:12, unknown for these elements at the present, was shown. Structural parameter data were presented. It was shown that all MN4 groupings have tetragonal-pyramidal structure. It was noted that the bond lengths formed by nitrogen atoms and an M atom were equal to each other only in the case of M = Ti, V, Cr and Co, whereas for other Ms, they were slightly different; moreover, the bond angles formed by nitrogen atoms and an M atom were equal to 90.0°, or practically did not differ from this value. Thermodynamic parameters, NBO analysis data and HOMO/LUMO images for this compound were also presented. Good agreement between the calculated data obtained using the above three quantum chemical methods was also noted.     

On a new method of investigating large technological systems—II Program structure of the network procedure

The present study deals with a digital computer version of the method described in the previous theoretical part. The study describes program structure of the so-called procedure and provides guidance for its practical use. As illustration a problem associated with a chemical plant is disclosed, the size of which demonstrates vividly its performance.     

ITEA—interactive trajectories and events analysis: exploring sequences of spatio-temporal events in movement data

Widespread use of GPS and similar technologies makes it possible to collect extensive amounts of trajectory data. These data sets are essential for reasonable decision making in various application domains. Additional information, such as events taking place along a trajectory, makes data analysis challenging, due to data size and complexity. We present an integrated solution for interactive visual analysis and exploration of events along trajectories data. Our approach supports analysis of event sequences at three different levels of abstraction, namely spatial, temporal, and events themselves. Customized views as well as standard views are combined to form a coordinated multiple views system. In addition to trajectories and events, we include on-the-fly derived data in the analysis. We evaluate our integrated solution using the IEEE VAST 2015 Challenge data set. A successful detection and characterization of malicious activity indicate the usefulness and efficiency of the presented approach.     

Ascorbic Acid-Assisted Eco-friendly Synthesis of NiCo<Subscript>2</Subscript>O<Subscript>4</Subscript> Nanoparticles as an Anode Material for High-Performance Lithium-Ion Batteries

We have synthesized NiCo₂O₄ nanoparticles (NCO NPs) using an ascorbic acid-assisted co-precipitation method for the first time. When NCO NPs are used as an anode material for lithium-ion batteries, the cell exhibits superior lithium storage properties, such as high capacity (700 mA h g^?1 after 300 cycles at 200 mA g^?1), excellent rate capabilities (applied current density range 100–1200 mA g^?1), and impressive cycling stability (at 1200 mA g^?1 up to 650 cycles). The enhanced electrochemical properties of NCO NPs are due to the nanometer dimensions which not only offers a smooth charge-transport pathway and short diffusion paths of the lithium ions but also adequate spaces for volume expansion during Li storage. Hence, this eco-friendly synthesis approach will provide a new strategy for the synthesis of various nanostructured metal oxide compounds, for energy conversion and storage systems applications.     

Prevalence and risk factors for Salmonella and Campylobacter spp. carcass contamination in broiler chickens slaughtered in Quebec, Canada

An observational study was conducted to estimate prevalence and risk factors for Salmonella and Campylobacter spp. carcass contamination in broiler chickens. Eighty-two lots were sampled in four slaughterhouses located in the province of Québec, Canada, over a 10-month period. Carcass contamination was evaluated by the carcass rinse technique for about 30 birds per lot. Exposure to potential risk factors was evaluated based on data from questionnaires, meteorology, and cecal cultures. Multivariable binomial negative regression models were used for risk factor analysis at the lot level. The prevalence of Salmonella-positive carcasses was 21.2% (95% confidence interval: 15.7 to 26.7%). Significant risk factors (P < 0.05) associated with a higher proportion of positive carcasses within lots were Salmonella-positive cecal culture, low rainfall during transportation to the slaughterhouse, temperature of > or = 0 degree C during transportation to the slaughterhouse, and a > or = 4-h waiting period in shipping crates before slaughtering. The prevalence of Campylobacter-positive carcasses was 35.8% (95% confidence interval: 27.1 to 44.5%). Lots containing birds with Campylobacter-positive cecal culture results, lots of birds that were slaughtered at the end of the week, and lots with at least 20% of birds with digestive contents detected in the jejunum at time of slaughtering had a significantly higher proportion (P < 0.05) of contaminated carcasses. These results support the importance of preharvest control measures implemented during rearing to reduce contamination of the final product. Weather during transportation to slaughter and the day of the week that birds were slaughtered also were associated with carcass contamination; further studies are needed to determine the underlying mechanisms by which these factors influence carcass contamination.