Optimization of 1,2,5‐Thiadiazole Carbamates as Potent and Selective ABHD6 Inhibitors

At present, inhibitors of α/β‐hydrolase domain 6 (ABHD6) are viewed as a promising approach to treat inflammation and metabolic disorders. This article describes the development of 1,2,5‐thiadiazole carbamates as ABHD6 inhibitors. Altogether, 34 compounds were synthesized, and their inhibitory activity was tested using lysates of HEK293 cells transiently expressing human ABHD6 (hABHD6). Among the compound series, 4‐morpholino‐1,2,5‐thiadiazol‐3‐yl cyclooctyl(methyl)carbamate (JZP‐430) potently and irreversibly inhibited hABHD6 (IC₅₀=44 nM ) and showed ～230‐fold selectivity over fatty acid amide hydrolase (FAAH) and lysosomal acid lipase (LAL), the main off‐targets of related compounds. Additionally, activity‐based protein profiling indicated that JZP‐430 displays good selectivity among the serine hydrolases of the mouse brain membrane proteome. JZP‐430 has been identified as a highly selective, irreversible inhibitor of hABHD6, which may provide a novel approach in the treatment of obesity and type II diabetes.     

Utilization of Cognitive Support in Episodic Free Recall as a Function of Apolipoprotein E and Vitamin B?? or Folate Among Adults Aged 75 Years and Older.

Apolipoprotein E (APOE), vitamin B??, and folate were examined in relation to free recall among 167 community-based older adults. Cognitive support at encoding and retrieval was also taken into account. Participants were classified as APOE e4 or non-e4 allele carriers and as either low or normal vitamin B?? or folate status. A significant association was identified between low vitamin B?? and the e4 genotype in respect to free recall, but only in circumstances of low cognitive support. This result remained after removing dementia cases that occurred up to 6 years after testing. A similar, but nonsignificant, trend was evident in relation to folate. The research is discussed with reference to vulnerability models and genetic influences on brain reserves. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Potential of agrifood wastes in mitigation of climate change and eutrophication - Two case regions

The aim of the study was to explore the currently unexploited potential of agrifood waste and by-product biomasses for energy recovery and nutrient recycling, to mitigate climate change and eutrophication. The technical potential was assessed in two different case regions in Finland using two contrasting processing technologies, one oriented to recycle carbon and the other one to maximise replacement of fossil energy. The reduction in nutrient surplus through efficient recycling of biomass and consequent decline in fertiliser use was calculated. The reduction in GHG emissions was estimated based on the replacement of fossil energy and the diminished fertiliser manufacture. It was established that the full potential of use of the biomass to reduce GHG emissions can only be exploited in biorefineries that both produce energy and efficiently recycle nutrients. Such biorefineries have the potential to significantly mitigate climate change and prevent eutrophication. The potential reduction in GHG emissions corresponded to a third of agricultural emissions, and the reduction in fertiliser manufacture contributed with an additional fifth of that. The energy recovery corresponded to 5-10% of the fossil energy used in the regions, and the reduction in energy use for manufacture of fertilisers represented an additional 14-20% in comparison with that. The potential for nutrient recycling corresponded to 99-120% of P and 45-72% of N in the yields harvested in the regions. The choice of technology had a more pronounced impact on energy recovery, GHG emissions and C budget than on nutrient recycling.     

Supplier capabilities in large shipbuilding projects

Project-based firms concentrate on their core capabilities outsourcing non-core activities. As project contractors increasingly use external suppliers to complement their own capability base, the importance of supplier selection is emphasized. Supplier choices should rely on accurate knowledge of the suppliers' capabilities. We examine the literature related TO supplier capabilities in collaborative, discontinuous project business. We use a qualitative, embedded single-case strategy in shipbuilding industry to explore the importance of supplier capabilities in one shipyard and examine how consistently the shipyard and its 20 suppliers assess the capabilities of the suppliers. Our results show that the buyer prioritizes technical, operational and business capabilities over relational and developmental capabilities, and that the buyer and its suppliers diverge in their assessments of the suppliers' capabilities, creating potential misunderstandings and false expectations in the buyer–supplier relationships. We complement prior research by adding a new dimension of business capabilities into the supplier's capability base in the field of project business.     

Ozonation for the Degradation of Organic Compounds from Nuclear Laundry Water

In this study, the efficiency of ozone to degrade organic compounds of nuclear laundry water was studied at different pH and temperatures and at elevated temperature with hydrogen peroxide. The degradation of non-ionic surfactant and other organic compounds was analyzed by COD, TOC, BOD and molecular weight distribution measurements. Zeta potential measurements were also performed in order to interpret the obtained results. The most favorable degradation conditions were at pH 7 with 43%, 34% and 61% reductions of COD, TOC and BOD, respectively.     

Supplier integration in complex delivery projects: Comparison between different buyer–supplier relationships

Research on project procurement management has centered on identifying the right suppliers and managing contracts to allocate risks and responsibilities. However, working with suppliers requires continuous integration activities from the buyer during project execution. This paper asks how buyers integrate their suppliers to the project organization during project execution, and how different types of buyer–supplier relationships differ in their supplier integration. We collected interview data in two complex delivery projects, both unique in their buyer–supplier relationships. We explored supplier integration practices from both the buyer’s and the supplier’s perspective, and sought cross-case differences possibly attributable to the different inter-organizational relationships. Based on the analysis, the nature of the buyer–supplier relationship appears to be associated with the type of integration practices used. The results of the study have implications on how supplier integration should be configured in different buyer–supplier relationships.     

Optimization of a time-resolved immunofluorometric assay for tumor-associated trypsin inhibitor (TATI) using the streptavidin-biotin system

We have developed two 'sandwich'-type time-resolved immunofluorometric assays (IFMA) for tumor-associated trypsin inhibitor (TATI) using monoclonal and polyclonal antibodies. In the standard assay the monoclonal antibody was immobilized onto the walls of polystyrene microstrip wells and the polyclonal reagent was labeled with a europium chelate. We tested various assay conditions in order to optimize the assay for sensitivity and measuring range. Purification of the labeled antibody by hydrophobic interaction chromatography was found to be the most important single factor affecting sensitivity. Assay sensitivity and range were also improved by acid treatment of the solid phase antibody. To improve the sensitivity further the streptavidin/biotin (SAB) system was incorporated into the IFMA technique. In this simple and fast streptavidin/biotin IFMA (SAB-IFMA) we used streptavidin-coated wells to which we added biotinylated monoclonal antibody and a serum or urine sample. After incubation for 1.5 h and washing, the polyclonal europium-labeled tracer antibody was added. After incubation for 1 h the wells were washed and the Eu fluorescence measured. The assay performance of the SAB-IFMA was compared to the standard IFMA and radioimmunoassay (RIA). The detection limit was 0.05 microgram/l and the analytical range 3000-fold. The mean analytical recovery was 101%. Other advantages of the SAB-IFMA were high sensitivity and the low amounts of monoclonal antibody required, only 1/50 of that used in the standard IFMA.     

Teaching the Fuzzy Front End of Innovation: Experimenting with Team Learning and Cross‐Organizational Integration

How can the extremely uncertain front end of innovation – managing the fuzzy front end – be taught to graduate students? This paper describes and analyses experiments with experiential, problem‐based learning focused on the front end of innovation. The focus is on the learning and cross‐organizational integration of student teams; factors that have been identified as central to the success of teams involved in the front end of innovation. An experiential course, ‘From an idea to a business plan in product development’, was developed in conjunction with an actual company, and piloted with four student groups in 2007 and 2008. Data on this novel course were collected through participant observation, team self‐assessment and questionnaires. This paper reports favourable results for the effectiveness of the course design; it discusses the impact of team size and cross‐organizational team composition on team performance; and identifies the implications for teaching the front end of innovation.     

Addition of Dispersoid Titanium Oxide Inclusions in Steel and Their Influence on Grain Refinement

In this article, the addition of dispersoid titanium oxide inclusions into liquid steel, the effect of additions on the inclusions found in the steel and on grain refinement, and acicular ferrite formation were studied. Different TiO₂-containing materials and addition procedures into liquid steel were tested in experimental heats to obtain inclusions that promote grain refinement and acicular ferrite formation in C-Mn-Cr steel. Different additives with metallic Ti and TiO₂ were added into the steel melt just before casting or into the mold during casting to create Ti-containing inclusions. The aluminum content in steel was lowered by an addition of iron oxide. The samples taken from steel melts and ingots were studied with a scanning electron microscope to find inclusions and to analyze them. Thermodynamic calculations showed that the Al content should be low (<50 ppm) to obtain Ti oxide dominating inclusions, whereas Al₂O₃ were formed at higher Al contents. When TiO₂ was added late before casting, the oxide inclusions were Ti oxides and were mixed with Ti, Al, and Mn oxides. Small inclusions around 1 μm were detected in the samples with TiO _x or TiN as the main component. It could be concluded that the additions resulted in a clearly higher number and in a smaller size of TiO _x inclusions than just by adding metallic Ti. Selected samples were brought for subsequent hot rolling and heat-treatment experiments to find out the grain-refining effect and the eventual formation of acicular ferrite. Grain refinement was observed clearly, but the presence of acicular ferrite could not be confirmed definitely.     

Prevalence and diversity of Clostridium botulinum types A, B, E and F in honey produced in the Nordic countries

A total of 294 honey samples produced in Denmark, Norway and Sweden were studied for the presence of Clostridium botulinum types A, B, E and F by using a multiplex-PCR method. The samples consisted of honeycombs taken directly from beehives, and extracted honey representing several hives or apiaries. The prevalence of C. botulinum showed a significant variation between Denmark, Norway and Sweden, the proportions of positive samples being 26%, 10% and 2%, respectively. The major serotype detected was type B. When analysed with pulsed-field gel electrophoresis (PFGE) using restriction enzyme SacII, the 24 strains isolated produced eight different PFGE patterns. At a similarity level of 95%, four clusters were produced, three of which contained 20 of the 24 analysed strains. One of the clusters included isolates from both Denmark and Norway.