Discovery of GPR183 Agonists Based on an Antagonist Scaffold

The G protein-coupled receptor GPR183/EBI2, which is activated by oxysterols, is a therapeutic target for inflammatory and metabolic diseases where both antagonists and agonists are of potential interest. Using the piperazine diamide core of the known GPR183 antagonist (E)-3-(4-bromophenyl)-1-(4-(4-methoxybenzoyl)piperazin-1-yl)prop-2-en-1-one (NIBR189) as starting point, we identified and sourced 79 structurally related compounds that were commercially available. In vitro screening of this compound collection using a Ca²⁺ mobilization assay resulted in the identification of 10 compounds with agonist properties. To enable establishment of initial structure-activity relationship trends, these were supplemented with five in-house compounds, two of which were also shown to be GPR183 agonists. Taken together, our findings suggest that the agonist activity of this compound series is dictated by the substitution pattern of one of the two distal phenyl rings, which functions as a molecular efficacy-switch.     

Solubility of some transition metal oxides in cryolite-alumina melts: Part II. Solubility of TiO2

The solubility of TiO₂ in cryolite-alumina melts at 1020 °C was measured; it decreased with increasing alumina concentration up to ∼3.5 wt pct total oxide and then increased at higher alumina concentrations. The solubility was found to be 3.1 wt pct Ti in cryolite, and 2.7 wt pct Ti in an alumina-saturated melt. Modeling indicated that the most probable titanium species are TiOF₂ and Na₂TiO₃, which coexist in the solution; the former dominates at low alumina concentrations and the latter at high alumina concentrations. Additional unknown amounts of fluoride may also be associated with these species. Determination of the solubility of TiO₂ in alumina-saturated melts as a function of temperature showed that the solubility increased from 1.9 wt pct Ti at 975 °C to 2.8 wt pct Ti at 1035 °C, the apparent partial molar enthalpy of dissolution of TiO₂ being 88±4 kJ mol⁻¹.     

Liquidus temperatures for primary crystallization of cryolite in molten salt systems of interest for aluminum electrolysis

Temperatures for primary crystallization of Na₃AlF₆ in multicomponent electrolyte systems of interest for the aluminum electrolysis process were determined by thermal analysis. The results are presented as binary and quasibinary diagrams and discussed in view of the literature data. An empirical equation describing liquidus temperatures for primary crystallization of Na₃AlF₆ was derived: $$\begin{gathered} t/(^\circ C) = 1011 + 0.50[AlF_3 ] - 0.13[AIF_3 ] - \frac{{3.45[CaF_2 ]}}{{1 + 0.0173[CaF_2 ]}} \hfill \\ + 0.124[CaF_2 ] \cdot [AlF_3 ] - 0.00542([CaF_2 ] \cdot [AlF_3 ])^{1.5} \hfill \\ - \frac{{7.93[Al_2 O_3 ]}}{{1 + 0.0936[Al_2 O_3 ] - 0.0017[Al_2 O_3 ]^2 - 0.0023[AlF_3 ] \cdot [Al_2 O_3 ]}} \hfill \\ - \frac{{8.90[LiF]}}{{1 + 0.0047[LiF] + 0.0010[AlF3]^2 }} - 3.95[MgF_2 ] - 3.95 \hfill \\ \end{gathered} $$ wheret is the temperature in degree Celsius and the square brackets denote the weight percent of components in the system Na₃AlF₆-AlF₃-CaF₂-Al₂O₃-LiF-MgF₂-KF. The composition limitations are [AlF₃] ≈ [CaF₂] ≈ [LiF] < 20 wt pct, [MgF₂] ≈ [KF] < 5 wt pct, and [A1₂O₃] up to saturation.     

Orchestration of network instruments: a way to de-emphasize the partition between incremental change and innovation?

Incremental change and innovation are often regarded as two separate concepts, with some interconnections. Based on two practical cases that emphasize respectively incremental change and innovation, the article discusses whether a division between these concepts can be maintained. Action research is seen as having a central role, offering an integral working method in industrial networks.

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Salmonella in eggs: From shopping to consumption—A review providing an evidence-based analysis of risk factors

Nontyphoidal salmonellae are among the most prevalent foodborne pathogens causing gastrointestinal infections worldwide. A high number of cases and outbreaks of salmonellosis are associated with the consumption of eggs and egg products, and several of these occur at the household level. The aim of the current study is to critically evaluate the current status of knowledge on Salmonella in eggs from a consumer's perspective, analyzing the hazard occurrence and the good practices that should be applied to reduce salmonellosis risk. Following a HACCP (Hazard Analysis and Critical Control Point) based approach, some steps along the food journey were identified as Critical Consumer Handling (CCH)—steps in which consumers, through their behavior or choice, can significantly reduce the level of Salmonella in eggs and egg products. From shopping/collecting to consumption, each of these steps is discussed in this review to provide an evidence-based overview of risk factors of human salmonellosis related to egg consumption. The main message to consumers is to choose Salmonella-free eggs (those that some official entity or producer guarantees that does not contain Salmonella), when available, especially for dishes that are not fully heat treated. Second, as guaranteed Salmonella-free eggs are only available in a few countries, refrigerated storage from the point of collection and proper cooking will significantly reduce the risk of salmonellosis. This will require a revision of the actual recommendations/regulations, as not all ensure that eggs are maintained at temperatures that prevent growth of Salmonella from collection until the time of purchasing.     

Direct Electrical Heating of Subsea Pipelines—Technology Development and Operating Experience

The formation of hydrates in the subsea production of oil and gas is a well-known problem. As the unprocessed well stream cools down, hydrates start to form around 25 degC, depending on the water cut and pressure in the pipeline. Several solutions are available to solve this problem. Generally, chemicals (i.e., methanol) have been used. Methanol reduces the critical temperature where hydrates are formed. Alternatively, hydrates can be prevented by using thermal insulation in combination with direct electrical heating (DEH). Thus, the well stream is kept above the critical temperature for hydrate formation. DEH heats the pipeline by forcing a large electric current to flow through the pipeline steel. The system model for design and sizing of the system is presented. DEH uses a single-phase system where the heated pipeline is electrically connected to the surrounding sea water. Thus, the system current is divided between sea water and pipeline, requiring additional sacrificial anodes on the pipeline. The anode system for a pipeline with DEH is discussed. There are currently more than 100 km of DEH pipelines on the Norwegian Continental Shelf. The operating experience from these installations is discussed. This paper presents the research and development for application of the system for pipelines with lengths up to 50 km     

THE RETURN OF ATLANTIC SALMON (SALMO SALAR L.) AND IMPROVED WATER QUALITY IN URBAN RIVERS IN OSLO,NORWAY

Most rivers and streams in the city of Oslo, Norway, rise in the surrounding forests, and all run through industrial and urban areas before they reach the sea. Most of these rivers have a long history of poor water quality in the middle and lower reaches until the early 1980s. This was reflected in low benthic diversity and the absence of fish. However, at the end of the 1970s, considerable efforts were made to limit industrial discharges, pollution episodes, and urban runoff, resulting in a substantial improvement in water quality. This improvement in water quality resulted in major changes in the benthos and fish populations of the rivers, especially the river Akerselva, which runs through the city centre. Here Atlantic salmon (Salmo salar) became extinct in the mid‐1800s and did not return until 1983. Atlantic salmon and sea trout (Salmo trutta) now spawn in the lower reaches, and the river supports juvenile populations of these salmonids. In line with the improvement in water quality, benthic biodiversity has also increased. These improvements have been documented based on long‐term monitoring of benthos and fish. Increased benthic diversity and presence of fish also enabled the authorities to trace the source of several pollution episodes that led to fish kills. The European Union Water Framework Directive will bring further pressure to maintain a stable and good ecological status for the Oslo rivers, although it may be difficult to attain this goal in an urban environment. Copyright © 2013 John Wiley & Sons, Ltd.     

Microfluidic pump based on the phenomenon of electroosmosis of the second kind

A micropump based on strong polarization of ion-exchange beads and corresponding actuation by electroosmosis of the second kind was designed and fabricated. Experimental results from operation with AC and DC voltage showed a close to second order relationship between flow and voltage, in good agreement with theory. The difference between experimental and theoretical flow rates and pressures is attributed to the hydrodynamic resistance of the channel network. A modified pump design which should yield higher flow rates and pressures was suggested.     

Transport priorities,risk perception and worry associated with mode use and preferences among Norwegian commuters

There is currently scant research on the role of transport priorities, risk perception and worry for travel mode use and preferences. The present study aims to examine these factors in relation to mode use and preferences among Norwegian commuters. A web-based survey was conducted in a randomly obtained representative sample of daily commuters in the extended greater Oslo area (n = 690). The results showed that those who prioritized efficiency and flexibility tended to commute by car, while those who prioritized safety and comfort used public (e.g. metro, tram, and train) or active (e.g. walking and cycling) transport. In a free choice scenario, the respondents who prioritized flexibility reported a preference for using a car, whereas those who prioritized safety and comfort preferred public and active transport for their commuter travels. Risk perception of high impact events, such as terrorism and major accidents, as well as risk perception related to personal impact risks (theft, violence etc.) were related to car use on commuter travels. Transport-related worry exerted weak influences on mode use and preferences. Increased speed on rail transport and more frequent departures may be effective in reducing car use on commuter travels. Risk communication should focus on highlighting the low risk of experiencing security and safety issues in the public transport sector, and this message should be complemented by efforts to reduce the probability of negative events affecting public transport.     

Different patterns of biofilm formation in Staphylococcus aureus under food-related stress conditions

Staphylococcus aureus and its biofilm formation are recognized as a serious clinical problem. S. aureus is also a food borne pathogen, and little is known regarding biofilm formation of food-related strains. We have studied biofilm formation of both food-related and clinical S. aureus strains grown under different stress conditions (temperature, sodium chloride, glucose and ethanol) relevant for food processing. Strong biofilm formers were identified among food-related S. aureus strains, and biofilm formation was affected by environmental conditions relevant for the food industry. The results showed that temperatures suboptimal for growth increased the production of biofilm. The combined presence of sodium chloride and glucose enhanced the biofilm formation. Both temperature and osmolarity affected the expression of several biofilm associated genes (e.g. icaA and rbf). Variations in gene expression (e.g. icaA, agrA and sigB) between strains were also observed. Our results support the existence of both ica-dependent and ica-independent mechanisms of biofilm production in S. aureus. The phenotypic and genotypic results showed highly diverse and complex patterns of biofilm formation in S. aureus. This clearly demonstrates that caution must be exercised before drawing general conclusions about gene expression in S. aureus in relation to regulation of biofilm formation. The results are relevant for food safety as they indicate that food processing conditions could promote biofilm formation by S. aureus.