Shovel ready? An empirical investigation of stalled residential sites.

Drawing upon a national database of unimplemented planning permissions and 18 in-depth case studies, this paper provides both a quantitative and qualitative analysis of the phenomenon of stalled sites in England. The practical and conceptual difficulties of classifying sites as stalled are critically reviewed. From the literature, it is suggested that planning permission may not be implemented due to lack of financial viability, strategic behaviour by landowners and house-builders and other problems associated with the development process. Consistent with poor viability, the analysis of the national database indicates that a substantial proportion of the stalled sites is high density apartment development and/or is located in low house value areas. The case studies suggest that a combination of interlinked issues may need to be resolved before a planning permission can be implemented. These include; the sale of the land to house-builders, re-negotiation of the planning permission and, most importantly, improvement in housing market conditions.

Investigation of cooperativity in the binding of ligands to the D-2 dopamine receptor

The D 2 dopamine receptor exists as dimers or as higher-order oligomers, as determined from data from physical experiments. In this study, we sought evidence that this oligomerization leads to cooperativity by examining the binding of three radioligands ([H-3] nemonapride, [H-3] raclopride, and [H-3] spiperone) to D 2 dopamine receptors expressed in membranes of Sf9 cells. In saturation binding experiments, the three radioligands exhibited different B-max values, and the B-max values could be altered by the addition of sodium ions to assays. Despite labeling different numbers of sites, the different ligands were able to achieve full inhibition in competition experiments. Some ligand pairs also exhibited complex inhibition curves in these experiments. In radioligand dissociation experiments, the rate of dissociation of [H-3] nemonapride or [H-3] spiperone depended on the sodium ion concentration but was independent of the competing ligand. Although some of the data in this study are consistent with the behavior of a cooperative oligomeric receptor, not all of the data are in agreement with this model. It may, therefore, be necessary to consider more complex models for the behavior of this receptor.

Investigation of the mechanism of agonist and inverse agonist action at D-2 dopamine receptors

This study investigated, for the D-2 dopamine receptor, the relation between the ability of agonists and inverse agonists to stabilise different states of the receptor and their relative efficacies. K-i values for agonists were determined in competition, versus the binding of the antagonist [H-3]spiperone. Competition data were fitted best by a two-binding site model (with the exception of bromocriptine, for which a one-binding site model provided the best fit) and agonist affinities for the higher (K-h) (G protein-coupled) and lower affinity (K-l) (G protein-uncoupled) sites determined. Ki values for agonists were also determined in competition versus the binding of the agonist [H-3]N-propylnorapomorphine (NPA) to provide a second estimate of K-h,. Maximal agonist effects (E-max) and their potencies (EC50) were determined from concentration-response curves for agonist stimulation of guanosine-5'-O-(3-[S-32] thiotriphosphate) ([S-35]GTPgammaS) binding. The ability of agonists to stabilise the G protein-coupled state of the receptor (K-l/K-h, determined from ligand-binding assays) did not correlate with either of two measures of relative efficacy (relative E-max, Kl/EC50) of agonists determined in [S-35]GTPgammaS-binding assays, when the data for all of the compounds tested were analysed For a subset of compounds, however, there was a relation between K-l/K-h and E-max.. Competition-binding data versus [H-3]spiperone and [H-3]NPA for a range of inverse agonists were fitted best by a one-binding site model. K-i values for the inverse agonists tested were slightly lower in competition versus [H-3]NPA compared to [H-3]spiperone. These data do not provide support for the idea that inverse agonists act by binding preferentially to the ground state of the receptor. (C) 2004 Elsevier Inc. All rights reserved.

Development of novel brush-type chiral stationary phases based on terpenoid selectors: HPLC evaluation and theoretical investigation of enantioselective binding interactions

The terpenoid chiral selectors dehydroabietic acid, 12,14-dinitrodehydroabietic acid and friedelin have been covalently linked to silica gel yielding three chiral stationary phases CSP 1, CSP 2 and CSP 3, respectively. The enantiodiscriminating capability of each one of these phases was evaluated by HPLC with four families of chiral aromatic compounds composed of alcohols, amines, phenylalanine and tryptophan amino acid derivatives and beta-lactams. The CSP 3 phase, containing a selector with a large friedelane backbone is particularly suitable for resolving free alcohols and their derivatives bearing fluorine substituents, while CSP 2 with a dehydroabietic architecture is the only phase that efficiently discriminates 1, 1'-binaphthol atropisomers. CSP 3 also gives efficient resolution of the free amines. All three phases resolve well the racemates of N-trifluoracetyl and N-3,5-dinitrobenzoyl phenylalanine amino acid ester derivatives. Good enantioseparation of beta-lactams and N-benzoyl tryptophan amino acid derivatives was achieved on CSP 1. In order to understand the structural factors that govern the chiral molecular recognition ability of these phases, molecular dynamics simulations were carried out in the gas phase with binary diastereomeric complexes formed by the selectors of CSP 1 and CSP 2 and several amino acid derivatives. Decomposition of molecular mechanics energies shows that van der Waals interactions dominate the formation of the diastereomeric transient complexes while the electrostatic binding interactions are primarily responsible for the enantioselective binding of the (R)- and (S)-analytes. Analysis of the hydrogen bonds shows that electrostatic interactions are mainly associated with the formation of N-(HO)-O-...=C enantio selective hydrogen bonds between the amide binding sites from the selectors and the carbonyl groups of the analytes. The role of mobile phase polarity, a mixture of n-hexane and propan-2-ol in different ratios, was also evaluated through molecular dynamics simulations in explicit solvent. (c) 2006 Elsevier Ltd. All rights reserved.

Investigation of cooperativity in the binding of ligands to the D-2 dopamine receptor

The D 2 dopamine receptor exists as dimers or as higher-order oligomers, as determined from data from physical experiments. In this study, we sought evidence that this oligomerization leads to cooperativity by examining the binding of three radioligands ([H-3] nemonapride, [H-3] raclopride, and [H-3] spiperone) to D 2 dopamine receptors expressed in membranes of Sf9 cells. In saturation binding experiments, the three radioligands exhibited different B-max values, and the B-max values could be altered by the addition of sodium ions to assays. Despite labeling different numbers of sites, the different ligands were able to achieve full inhibition in competition experiments. Some ligand pairs also exhibited complex inhibition curves in these experiments. In radioligand dissociation experiments, the rate of dissociation of [H-3] nemonapride or [H-3] spiperone depended on the sodium ion concentration but was independent of the competing ligand. Although some of the data in this study are consistent with the behavior of a cooperative oligomeric receptor, not all of the data are in agreement with this model. It may, therefore, be necessary to consider more complex models for the behavior of this receptor.

The role of rodents as carriers of disease on UK farms: a preliminary investigation

In the UK, Campylobacter spp. and Lymphocytic Choriomeningitis Virus (LCMV), an Old World arenavirus, cause two zoonoses of concern that may be transmissible from rodents to humans and livestock. The aims of this preliminary investigation were to examine the occurrence of Campylobacter spp. and LCMV in Norway rats Rattus norvegicus on UK farms and to identify and characterise the Sequence Types of the Campylobacter isolates. Samples were collected from wild Norway rats and fresh Norway rat faeces. Multi Locus Sequence Typing (MLST) was performed on C. spp. isolates and samples were tested for arenavirus RNA by RT-PCR. Six C. spp. isolates were identified. One isolate was C. lari and five isolates were C. jejuni. Following MSLT profiling, three unique C. jejuni sequence types were identified. Two of which are novel and the third is typically associated with livestock and human infection. Nine positive results for LCMV were obtained giving an overall prevalence of 25% across four sites. This is higher than previously reported for this species.

Sensitivity analysis of an ocean carbon cycle model in the North Atlantic: an investigation of parameters affecting the air-sea CO2 flux, primary production and export of detritus

The sensitivity of the biological parameters in a nutrient-phytoplankton-zooplankton-detritus (NPZD) model in the calculation of the air-sea CO2 flux, primary production and detrital export is analysed. We explore the effect on these outputs of variation in the values of the twenty parameters that control ocean ecosystem growth in a 1-D formulation of the UK Met Office HadOCC NPZD model used in GCMs. We use and compare the results from one-at-a-time and all-at-a-time perturbations performed at three sites in the EuroSITES European Ocean Observatory Network: the Central Irminger Sea (60° N 40° W), the Porcupine Abyssal Plain (49° N 16° W) and the European Station for Time series in the Ocean Canary Islands (29° N 15° W). Reasonable changes to the values of key parameters are shown to have a large effect on the calculation of the air-sea CO2 flux, primary production, and export of biological detritus to the deep ocean. Changes in the values of key parameters have a greater effect in more productive regions than in less productive areas. The most sensitive parameters are generally found to be those controlling well-established ocean ecosystem parameterisations widely used in many NPZD-type models. The air-sea CO2 flux is most influenced by variation in the parameters that control phytoplankton growth, detrital sinking and carbonate production by phytoplankton (the rain ratio). Primary production is most sensitive to the parameters that define the shape of the photosynthesis-irradiance curve. Export production is most sensitive to the parameters that control the rate of detrital sinking and the remineralisation of detritus.

Electronic charge transfer between ceria surfaces and gold adatoms: a GGA+U investigation

We use density functional theory calculations with Hubbard corrections (DFT+U) to investigate electronic aspects of the interaction between ceria surfaces and gold atoms. Our results show that Au adatoms at the (111) surface of ceria can adopt Au0, Au+ or Au� electronic configurations depending on the adsorption site. The strongest adsorption sites are on top of the surface oxygen and in a bridge position between two surface oxygen atoms, and in both cases charge transfer from the gold atom to one of the Ce cations at the surface is involved. Adsorption at other sites, including the hollow sites of the surface, and an O–Ce bridging site, is weaker and does not involve charge transfer. Adsorption at an oxygen vacancy site is very strong and involves the formation of an Au� anion. We argue that the ability of gold atoms to stabilise oxygen vacancies at the ceria surface by moving into the vacancy site and attracting the excess electrons of the defect could be responsible for the enhanced reducibility of ceria surfaces in the presence of gold. Finally, we rationalise the differences in charge transfer behaviour from site to site in terms of the electrostatic potential at the surface and the coordination of the species.

An investigation to enhance understanding of the stimulation of weed seedling emergence by soil disturbance

Enhanced understanding of soil disturbance effects on weed seedling recruitment will help guide improved management approaches. Field experiments were conducted at 16 site-years at 10 research farms across Europe and North America to (i) quantify superficial soil disturbance (SSD) effects on Chenopodium album emergence and (ii) clarify adaptive emergence behaviour in frequently disturbed environments. Each site-year contained factorial combinations of two seed populations (local and common, with the common population studied at all site-years) and six SSD timings [0, 50, 100, 150, 200 day-degrees (d°C, base temperature 3°C) after first emergence from undisturbed soil]. Analytical units in this study were emergence flushes. Flush magnitudes (maximum weekly emergence per count flush) and flush frequencies (flushes year 1) were compared between disturbed and undisturbed seedbanks. One year after burial, SSD promoted seedling emergence relative to undisturbed seedbanks by increasing flush magnitude rather than increasing flush frequency. Two years after burial, SSD promoted emergence through increased flush magnitude and flush frequency. The promotional effects of SSD on emergence were strongest within 500 d°C following SSD; however, low levels of SSDinduced emergence were detected as late as 3000 d°C following SSD. Accordingly, stale seedbed practices that eliminate weed seedlings should occur within 500 d°C of disturbance, because few seedlings emerge after this time. However, implementation of stale seedbed practices will probably cause slight increases in weed population densities throughout the year. Compared with the common population, local populations exhibited reduced variance in total emergence measured within sites and across SSD treatments, suggesting that C. album adaptation to local pedo-climatic conditions involves increased consistency in SSD-induced emergence.

Regulation of cell migration in cancer: investigation into the regulation of cancer cell blebbing in the extracellular matrix

Cell migration is a highly coordinated process and any aberration in the regulatory mechanisms could result in pathological conditions such as cancer. The ability of cancer cells to disseminate to distant sites within the body has made it difficult to treat. Cancer cells also exhibit plasticity that makes them able to interconvert from an elongated, mesenchymal morphology to an amoeboid blebbing form under different physiological conditions. Blebs are spherical membrane protrusions formed by actomyosin-mediated contractility of cortical actin resulting in increased hydrostatic pressure and subsequent detachment of the membrane from the cortex. Tumour cells use blebbing as an alternative mode of migration by squeezing through preexisting gaps in the ECM, and bleb formation is believed to be mediated by the Rho-ROCK signaling pathway. However, the involvement of transmembrane water and ion channels in cell blebbing has not been examined. In the present study, the role of the transmembrane water channels, aquaporins, transmembrane ion transporters and lipid signaling enzymes in the regulation of blebbing was investigated. Using 3D matrigel matrix as an in vitro model to mimic normal extracellular matrix, and a combination of confocal and time-lapse microscopy, it was found that AQP1 knockdown by siRNA ablated blebbing of HT1080 and ACHN cells, and overexpression of AQP1-GFP not only significantly increased bleb size with a corresponding decrease in bleb numbers, but also induced bleb formation in non-blebbing cell lines. Importantly, AQP1 overexpression reduces bleb lifespan due to faster bleb retraction. This novel finding of AQP1-facilitated bleb retraction requires the activity of the Na+/H+ pump as inhibition of the ion transporter, which was found localized to intracellular vesicles, blocked bleb retraction in both cell lines. This study also demonstrated that a differential regulation of cell blebbing by AQP isoforms exists as knockdown of AQP5 had no effect on bleb formation. Data from this study also demonstrates that the lipid signaling PLD2 signals through PA in the LPA-LPAR-Rho-ROCK axis to positively regulate bleb formation in both cell lines. Taken together, this work provides a novel role of AQP1 and Na+/H+ pump in regulation of cell blebbing, and this could be exploited in the development of new therapy to treat cancer.

Investigation of the impact of anthropogenic heat flux within an urban land surface model and PILPS-urban

Results from the first international urban model comparison experiment (PILPS-Urban) suggested that models which neglected the anthropogenic heat flux within the surface energy balance performed at least as well as models that include the source term, but this could not be explained. The analyses undertaken show that the results from PILPS-Urban were masked by the signal from including vegetation, which was identified in PILPS-Urban as being important. Including the anthropogenic heat flux does give improved performance, but the benefit is small for the site studied given the relatively small magnitude of this flux relative to other terms in the surface energy balance. However, there is no further benefit from including temporal variations in the flux at this site. The importance is expected to increase at sites with a larger anthropogenic heat flux and greater temporal variations.