5‐(Piperidin‐4‐yl)‐3‐Hydroxypyrazole: A Novel Scaffold for Probing the Orthosteric γ‐Aminobutyric Acid Type A Receptor Binding Site

A series of bioisosteric N₁‐ and N₂‐substituted 5‐(piperidin‐4‐yl)‐3‐hydroxypyrazole analogues of the partial GABA_AR agonists 4‐PIOL and 4‐PHP have been designed, synthesized, and characterized pharmacologically. The unsubstituted 3‐hydroxypyrazole analogue of 4‐PIOL ( 2 a ; IC₅₀～300 μM ) is a weak antagonist at the α₁β₂γ₂ GABA_AR, whereas substituting the N₁‐ or N₂‐position with alkyl or aryl substituents resulted in antagonists with binding affinities in the high nanomolar to low micromolar range at native rat GABA_ARs. Docking studies using a α₁β₂γ₂ GABA_AR homology model along with the obtained SAR indicate that the N₁‐substituted analogues of 4‐PIOL and 4‐PHP, 2 a – k , and previously reported 3‐substituted 4‐PHP analogues share a common binding mode to the orthosteric binding site in the receptor. Interestingly, the core scaffold of the N₂‐substituted analogues of 4‐PIOL and 4‐PHP, 3 b – k , are suggested to flip 180° thereby adapting to the binding pocket and addressing a cavity situated above the core scaffold.     

Corrosion of concrete sewers--the kinetics of hydrogen sulfide oxidation

The widespread occurrence of polybrominated diphenyl ethers (PBDEs) in the environment has attracted considerable attention, leading to concerns about the extent and magnitude of wildlife and human exposure. In this work, we focus on the occurrence and fate of PBDEs in a Norwegian air-plant-herbivore-carnivore system. Specifically, we have analysed for PBDEs in moss, livers from various terrestrial herbivores (moose, grouse, and European roe deer) and, for the first time, livers from the top predator lynx. The samples were collected from different sites and time periods (1990-2004) to identify possible spatial and temporal trends in contaminant levels and patterns. The general finding was that PBDEs were found in all (biotic) samples, although at lower concentrations than previously observed in mammals from the marine environment. The PBDE levels in the herbivores ranged from less than 0.5 ng/g lipid weight to 9.4 ng/g lipid weight as the highest. The median PBDE concentration in lynx was approximately one order of magnitude higher than in the herbivores. In the lynx samples there was a predominance of BDE-153 whereas BDE-47 and 99 dominated in the herbivores. This probably reflects different bioaccumulation properties or metabolic transformation processes of the BDE-congeners, and food choice. Levels of PBDEs in both moss and herbivores showed a general decline towards the northern parts of Norway. No clear temporal trends were observed. The PBDE levels observed in this study were low and are probably of limited toxicological significance.     

A Bayesian spatial econometric analysis of the 2010 UK General Election

The Conservative Party won the 2010 General Election in the United Kingdom, gaining the most votes and seats of any single party. Using Bayesian spatial econometric methods, we show that significant spatial dependence exists in Conservative voting behaviour and select the spatial Durbin model as the best model to explain this phenomenon. This paper examines these spatial effects as well as the effects of a range of economic, socio‐economic, and political variables. Perhaps the most interesting result is that incumbency has effects beyond an incumbent's own constituency.     

An evaluation tool for design quality: PFI sheltered housing

The complex procurement process entailed by the private finance initiative (PFI) means that clients need new capacities to manage their relationships with bidders and to assess project proposals if the desired level of design quality is to be achieved. To assist local authorities in their client role, a new Architectural Design Quality Evaluation Tool was developed. The aim was to improve the quality of design in residential sheltered housing, procured through the PFI. The tool was developed for and applied to a programme that will see the replacement of a local authority's entire sheltered housing stock. The tool has two functions: (1) to inform the client's assessment process and assist with the selection of the preferred bidding consortium through a series of stages in the PFI process; and (2) to improve the quality of all the submitted designs through an iterative process. Although several existing mechanisms are available for evaluating the performance attributes of buildings, few also tackle the less tangible amenity attributes, which are vital to the feeling of home. The new tool emphasizes the amenity attributes without neglecting performance.     

Progress report from Denmark

Space heating is seen in Denmark as the area where there is greatest potential for saving in energy use; why and how is explained in this article from the Danish Building Research Institute. It summarises the new building code regulations for insulation, heating and ventilation as well as more recent rules for existing buildings. Further action planned for the future is also outlined and examples are given of the many R & D activities in the country.     

An examination of land use change due to irrigated agriculture in north‐eastern Jordan using geoinformatics

The Jordanian government has encouraged irrigated agriculture since the early 1990s by providing low cost loans to drill private wells. The impacts of this practice on land use change were examined within a small (362 km²) area of the Jordanian Badia using Geoinformatics. Aerial photographs, SPOT and Landsat TM imageries were used, in a GIS environment, to map and examine changes in the farming patterns since 1990. Field surveys and questionnaires were used to ground truth the remotely sensed data. The results indicate that the cultivated area has increased from just 28.5 ha in 1990 to over 1000 ha in 2000 and that the number of farms has increased from 2 to 32 over the same time period. Furthermore, farm locations are moved annually restricted by the position of the well and land availability; this also causes land use change.     

Climate-change impacts on hydrology and nutrients in a Danish lowland river basin

The Mike 11-TRANS modelling system was applied to the lowland Gjern river basin in Denmark to assess climate-change impacts on hydrology and nitrogen retention processes in watercourses, lakes and riparian wetlands. Nutrient losses from land to surface waters were assessed using statistical models incorporating the effect of changed hydrology. Climate-change was predicted by the ECHAM4/OPYC General Circulation Model (IPCC A2 scenario) dynamically downscaled by the Danish HIRHAM regional climate model (25 km grid) for two time slices: 1961-1990 (control) and 2071-2100 (scenario). HIRHAM predicts an increase in mean annual precipitation of 47 mm (5%) and an increase in mean annual air temperature of 3.2 degrees C (43%). The HIRHAM predictions were used as external forcings to the rainfall-runoff model NAM, which was set up and run for 6 subcatchments within and for the entire, Gjern river basin. Mean annual runoff from the river basin increases 27 mm (7.5%, p<0.05) when comparing the scenario to the control. Larger changes, however, were found regarding the extremes; runoff during the wettest year in the 30-year period increased by 58 mm (12.3%). The seasonal pattern is expected to change with significantly higher runoff during winter. Summer runoff is expected to increase in predominantly groundwater fed streams and decrease in streams with a low base-flow index. The modelled change in the seasonal hydrological pattern is most pronounced in first- or second-order streams draining loamy catchments, which currently have a low base-flow during the summer period. Reductions of 40-70% in summer runoff are predicted for this stream type. A statistical nutrient loss model was developed for simulating the impact of changed hydrology on diffuse nutrient losses (i.e. losses from land to surface waters) and applied to the river basin. The simulated mean annual changes in TN loads in a loamy and a sandy subcatchment were, respectively, +2.3 kg N ha(-1) (8.5%) and +1.6 kg N ha(-1) (6.9%). The rainfall-runoff model and the nutrient loss model were chained with Mike 11-TRANS to simulate the combined effects of climate-change on hydrology, nutrient losses and nitrogen retention processes at the scale of the river basin. The mean annual TN export from the river basin increased from the control to the scenario period by 7.7%. Even though an increase in nitrogen retention in the river system of 4.2% was simulated in the scenario period, an increased in-stream TN export resulted because of the simulated increase in the diffuse TN transfer from the land to the surface-waters.     

Storage temperature affects distribution of carbon, VFA, ammonia, phosphorus, copper and zinc in raw pig slurry and its separated liquid fraction

Chemical-mechanical separation of pig slurry into a solid fraction rich in dry matter, P, Cu and Zn and a liquid fraction rich in inorganic N but poor in dry matter may allow farmers to manage surplus slurry by exporting the solid fraction to regions with no nutrient surplus. Pig slurry can be applied to arable land only in certain periods during the year, so it is commonly stored prior to field application. This study investigated the effect of storage duration and temperature on chemical characteristics and P, Cu and Zn distribution between particle size classes of raw slurry and its liquid separation fraction. Dry matter, VFA, total N and ammonium content of both slurry products decreased during storage and were affected by temperature, showing higher losses at higher storage temperatures. In both products, total P, Cu and Zn concentrations were not significantly affected by storage duration or temperature. Particle size distribution was affected by slurry separation, storage duration and temperature. In raw slurry, particles larger than 1 mm decreased, whereas particles 250 μm-1 mm increased. The liquid fraction produced was free of particles >500 μm, with the highest proportions of P, Cu and Zn in the smallest particle size class (<25 μm). The proportion of particles <25 μm increased when the liquid fraction was stored at 5 °C, but decreased at 25 °C. Regardless of temperature, distribution of P, Cu and Zn over particle size classes followed a similar pattern to dry matter.     

Low temperature OMVPE growth of ZnSe withTertiary-butyl allyl selenide and dimethylzinc-triethylamine

The growth of high quality ZnSe by organometallic vapor phase epitaxy (OMVPE) has been investigated fortertiary-butyl allyl selenide (tBASe), combined with dimethylzinc-triethylamine (DMZn : NEt₃). Single crystalline ZnSe films were grown on GaAs at temperature as low as 350°C with a reasonable growth rate (~1 µm/h). Secondary ion mass spectrometry (SIMS) spectra show a negligible carbon incorporation in ZnSe films from tBASe even at high VI/II ratio, in contrast the carbon concentration of 10²¹ cm^-3 in ZnSe films grown from diallyl selenide (DASe)and methylallylselenide (MASe). Good surface morphology, crystalline and interface quality of ZnSe on (001) GaAs are confirmed by scanning electron microscopy, double crystal diffractometry (DCD) and Rutherford backscattering spectrometry (RBS). Photoluminescence at 10K shows sharp near-band-edge excitonic spectra.