Essential selfadjointness of singular magnetic Schrödinger operators on Riemannian manifolds

In this paper we extend the well-known Leinfelder–Simader theorem on the essential selfadjointness of singular Schrödinger operators to arbitrary complete Riemannian manifolds. This improves some earlier results of Shubin, Milatovic and others.

Human red blood cells at work: identification and visualization of erythrocytic eNOS activity in health and disease

A nitric oxide synthase (NOS)-like activity has been demonstrated in human red blood cells (RBCs), but doubts about its functional significance, isoform identity and disease relevance remain. Using flow cytometry in combination with the NO-imaging probe DAF-FM we find that all blood cells form NO intracellularly, with a rank order of monocytes > neutrophils > lymphocytes > RBCs > platelets. The observation of a NO-related fluorescence within RBCs was unexpected given the abundance of the NO-scavenger oxyhemoglobin. Constitutive normoxic NO formation was abolished by NOS inhibition and intracellular NO scavenging, confirmed by laser-scanning microscopy and unequivocally validated by detection of the DAF-FM reaction product with NO using HPLC and LC-MS/MS. Employing immunoprecipitation, ESI-MS/MS-based peptide sequencing and enzymatic assay we further demonstrate that human RBCs contain an endothelial NOS (eNOS) that converts L-3H-Arginine to L-3H-Citrulline in a Ca2+/Calmodulin-dependent fashion. Moreover, in patients with coronary artery disease, red cell eNOS expression and activity are both lower than in age-matched healthy individuals and correlate with the degree of endothelial dysfunction. Thus, human RBCs constitutively produce NO under normoxic conditions via an active eNOS isoform the activity of which is compromised in patients with coronary artery disease.

Improving promiscuous mammalian cell entry by the baculovirus AcMNPV

The insect baculovirus Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) enters many mammalian cell lines, prompting its application as a general eukaryotic gene delivery agent, but the basis of entry is poorly understood. For adherent mammalian cells we show that entry is favoured by low pH and increasing the available cell surface area through transient release from the substratum. Low pH also stimulated baculovirus entry into mammalian cells grown in suspension which, optimally, could reach 90% of the transduced population. The basic loop, residues 268-281, of the viral surface glycoprotein gp64 was required for entry and a tetra mutant with increasing basicity increased entry into a range of mammalian cells. The same mutant failed to plaque in Sf9 cells, instead showing individual cell entry and minimal cell to cell spread, consistent with an altered fusion phenotype. Viruses grown in different insect cells showed different mammalian cell entry efficiencies suggesting additional factors also govern entry.

Tropical-extratropical interactions over Southern Africa: three cases of heavy summer season rainfall

The synoptic evolution of three tropical–extratropical (TE) interactions, each responsible for extreme rainfall events over southern Africa, is discussed in detail. Along with the consideration of previously studied events, common features of these heavy rainfall producing tropical temperate troughs (TTTs) over southern Africa are discussed. It is found that 2 days prior to an event, northeasterly moisture transports across Botswana, set up by the Angola low, are diverted farther south into the semiarid region of subtropical southern Africa. The TTTs reach full maturity as a TE cloud band, rooted in the central subcontinent, which is triggered by upper-level divergence along the leading edge of an upper-tropospheric westerly wave trough. Convection and rainfall within the cloud band is supported by poleward moisture transports with subtropical air rising as it leaves the continent and joins the midlatitude westerly flow. It is shown that these systems fit within a theoretical framework describing similar TE interactions found globally. Uplift forcing for the extreme rainfall of each event is investigated. Unsurprisingly, quasigeostrophic uplift is found to dominate in the midlatitudes with convective processes strongest in the subtropics. Rainfall in the semiarid interior of South Africa appears to be a result of quasigeostrophically triggered convection. Investigation of TTT formation in the context of planetary waves shows that early development is sometimes associated with previous anticyclonic wave breaking south of the subcontinent, with full maturity of TTTs occurring as a potential vorticity trough approaches the continent from the west. Sensitivity to upstream wave perturbations and effects on anticyclonic wave breaking in the South Indian Ocean are also observed.

Building a tropical-extratropical cloud band metbot

An automated cloud band identification procedure is developed that captures the meteorology of such events over southern Africa. This “metbot” is built upon a connected component labelling method that enables blob detection in various atmospheric fields. Outgoing longwave radiation is used to flag candidate cloud band days by thresholding the data and requiring detected blobs to have sufficient latitudinal extent and exhibit positive tilt. The Laplacian operator is used on gridded reanalysis variables to highlight other features of meteorological interest. The ability of this methodology to capture the significant meteorology and rainfall of these synoptic systems is tested in a case study. Usefulness of the metbot in understanding event to event similarities of meteorological features is demonstrated, highlighting features previous studies have noted as key ingredients to cloud band development in the region. Moreover, this allows the presentation of a composite cloud band life cycle for southern Africa events. The potential of metbot to study multiscale interactions is discussed, emphasising its key strength: the ability to retain details of extreme and infrequent events. It automatically builds a database that is ideal for research questions focused on the influence of intraseasonal to interannual variability processes on synoptic events. Application of the method to convergence zone studies and atmospheric river descriptions is suggested. In conclusion, a relation-building metbot can retain details that are often lost with object-based methods but are crucial in case studies. Capturing and summarising these details may be necessary to develop deeper process-level understanding of multiscale interactions.

Cloud bands over southern Africa: seasonality, contribution to rainfall variability, and modulation by the MJO

Tropical-extratropical cloud band systems over southern Africa, known as tropical temperate troughs (TTTs), are known to contribute substantially to South African summer rainfall. This study performs a comprehensive assessment of the seasonal cycle and rainfall contribution of TTTs by using a novel object-based strategy that explicitly tracks these systems for their full life cycle. The methodology incorporates a simple assignment of station rainfall data to each event, thereby creating a database containing detailed rainfall characteristics for each TTT. This is used to explore the importance of TTTs for rain days and climatological rainfall totals in October–March. Average contributions range from 30 to 60 % with substantial spatial heterogeneity observed. TTT rainfall contributions over the Highveld and eastern escarpment are lower than expected. A short analysis of TTT rainfall variability indicates TTTs provide substantial, but not dominant, intraseasonal and interannual variability in station rainfall totals. TTTs are however responsible for a high proportion of heavy rainfall days. Of 52 extreme rainfall events in the 1979–1999 period, 30 are associated with these tropical-extratropical interactions. Cut-off lows were included in the evolution of 6 of these TTTs. The study concludes with an analysis of the question: does the Madden-Julian Oscillation influence the intensity of TTT rainfall over South Africa? Results suggest a weak but significant suppression (enhancement) of intensity during phase 1(6).

Development appraisal in practice: some evidence from the planning system

Due to the requirement to demonstrate financial feasibility of policy proposals and scheme-specific planning obligations, development viability and development appraisal have become core themes in the English planning system. The objective of this paper is to evaluate the application of development appraisal in practice. The paper reviews the literature and the models available to assess the viability of development and analyses a sample 19 development viability appraisals to identify practice. The paper concludes that the practice of development appraisal deviates significantly from the tenets of capital budgeting theory. In particular, in addition to a propensity to oversimplify the timing of income and expenditure, the way in which debt, developer’s return and value and cost change are handled in practice illustrates a major gap between mainstream capital budgeting theory and development appraisal in practice.

Voltage-gated potassium currents within the dorsal vagal nucleus: inhibition by BDS toxin

Voltage-gated potassium (Kv) channels are essential components of neuronal excitability. The Kv3.4 channel protein is widely distributed throughout the central nervous system (CNS), where it can form heteromeric or homomeric Kv3 channels. Electrophysiological studies reported here highlight a functional role for this channel protein within neurons of the dorsal vagal nucleus (DVN). Current clamp experiments revealed that blood depressing substance (BDS) and intracellular dialysis of an anti-Kv3.4 antibody prolonged the action potential duration. In addition, a BDS sensitive, voltage-dependent, slowly inactivating outward current was observed in voltage clamp recordings from DVN neurons. Electrical stimulation of the solitary tract evoked EPSPs and IPSPs in DVN neurons and BDS increased the average amplitude and decreased the paired pulse ratio, consistent with a presynaptic site of action. This presynaptic modulation was action potential dependent as revealed by ongoing synaptic activity. Given the role of the Kv3 proteins in shaping neuronal excitability, these data highlight a role for homomeric Kv3.4 channels in spike timing and neurotransmitter release in low frequency firing neurons of the DVN.

Localization and function of the Kv3.1b subunit in the rat medulla oblongata: focus on the nucleus tractus solitarii

The voltage-gated potassium channel subunit Kv3.1 confers fast firing characteristics to neurones. Kv3.1b subunit immunoreactivity (Kv3.1b-IR) was widespread throughout the medulla oblongata, with labelled neurones in the gracile, cuneate and spinal trigeminal nuclei. In the nucleus of the solitary tract (NTS), Kv3.1b-IR neurones were predominantly located close to the tractus solitarius (TS) and could be GABAergic or glutamatergic. Ultrastructurally, Kv3.1b-IR was detected in NTS terminals, some of which were vagal afferents. Whole-cell current-clamp recordings from neurones near the TS revealed electrophysiological characteristics consistent with the presence of Kv3.1b subunits: short duration action potentials (4.2 +/- 1.4 ms) and high firing frequencies (68.9 +/- 5.3 Hz), both sensitive to application of TEA (0.5 mm) and 4-aminopyridine (4-AP; 30 mum). Intracellular dialysis of an anti-Kv3.1b antibody mimicked and occluded the effects of TEA and 4-AP in NTS and dorsal column nuclei neurones, but not in dorsal vagal nucleus or cerebellar Purkinje cells (which express other Kv3 subunits, but not Kv3.1b). Voltage-clamp recordings from outside-out patches from NTS neurones revealed an outward K(+) current with the basic characteristics of that carried by Kv3 channels. In NTS neurones, electrical stimulation of the TS evoked EPSPs and IPSPs, and TEA and 4-AP increased the average amplitude and decreased the paired pulse ratio, consistent with a presynaptic site of action. Synaptic inputs evoked by stimulation of a region lacking Kv3.1b-IR neurones were not affected, correlating the presence of Kv3.1b in the TS with the pharmacological effects.

Accounting for the economic risk, caused by variation in disease severity, in fungicide dose decisions: exemplified for Mycosphaerella graminicola on winter wheat

A method is presented to calculate economic optimum fungicide doses accounting for the risk-aversion of growers responding to variability in disease severity between crops. Simple dose-response and disease-yield loss functions are used to estimate net disease-related costs (fungicide cost, plus disease-induced yield loss) as a function of dose and untreated severity. With fairly general assumptions about the shapes of the probability distribution of disease severity and the other functions involved, we show that a choice of fungicide dose which minimises net costs on average across seasons results in occasional large net costs caused by inadequate control in high disease seasons. This may be unacceptable to a grower with limited capital. A risk-averse grower can choose to reduce the size and frequency of such losses by applying a higher dose as insurance. For example, a grower may decide to accept ‘high loss’ years one year in ten or one year in twenty (i.e. specifying a proportion of years in which disease severity and net costs will be above a specified level). Our analysis shows that taking into account disease severity variation and risk-aversion will usually increase the dose applied by an economically rational grower. The analysis is illustrated with data on septoria tritici leaf blotch of wheat caused by Mycosphaerella graminicola. Observations from untreated field plots at sites across England over three years were used to estimate the probability distribution of disease severities at mid-grain filling. In the absence of a fully reliable disease forecasting scheme, reducing the frequency of ‘high loss’ years requires substantially higher doses to be applied to all crops. Disease resistant cultivars reduce both the optimal dose at all levels of risk and the disease-related costs at all doses.

Can valuation factors be prescribed? The case of collective enfranchisement and leasehold extension of flats in England and Wales

Recent concerns over the valuation process in collective leasehold enfranchisement and lease extension cases have culminated in new legislation. To underpin this, the Government (Department of Environment Transport and the Regions (DETR)) commissioned new research, which examined whether the valuation of the freehold in such cases could be simplified through the prescription of either yield or marriage value/relativity. This paper, which is based on that research, examines whether it is possible or desirable to prescribe such factors in the valuation process. Market, settlement and Local Valuation Tribunal (LVT) decisions are analysed, and the basis of 'relativity charts' used in practice is critically examined. Ultimately the imperfect nature of the market in freehold investment sales and leasehold vacant possession sales means that recommendations must rest on an analysis of LVT data. New relativity curves are developed from this data and used in conjunction with an alternative approach to valuation yields (based on other investment assets). However, the paper concludes that although the prescription of yields and relativity is possible, it is not fully defensible because of problems in determining risk premia; that the evidential basis for relativity consists of LVT decisions; and that a formula approach would tend to 'lead' the market as a whole.

A critical review of methodologies for measuring rental depreciation applied to UK commercial real estate

Real estate depreciation continues to be a critical issue for investors and the appraisal profession in the UK in the 1990s. Depreciation-sensitive cash flow models have been developed, but there is a real need to develop further empirical methodologies to determine rental depreciation rates for input into these models. Although building quality has been found to be an important explanatory variable in depreciation it is very difficult to incorporate it into such models or to analyse it retrospectively. It is essential to examine previous depreciation research from real estate and economics in the USA and UK to understand the issues in constructing a valid and pragmatic way of calculating rental depreciation. Distinguishing between 'depreciation' and 'obsolescence' is important, and the pattern of depreciation in any study can be influenced by such factors as the type (longitudinal or crosssectional) and timing of the study, and the market state. Longitudinal studies can analyse change more directly than cross-sectional studies. Any methodology for calculating rental depreciation rate should be formulated in the context of such issues as 'censored sample bias', 'lemons' and 'filtering', which have been highlighted in key US literature from the field of economic depreciation. Property depreciation studies in the UK have tended to overlook this literature, however. Although data limitations and constraints reduce the ability of empirical property depreciation work in the UK to consider these issues fully, 'averaging' techniques and ordinary least squares (OLS) regression can both provide a consistent way of calculating rental depreciation rates within a 'cohort' framework.

Migration, immobility and displacement outcomes following extreme events

There is growing international concern at the rise in the severity of impact and frequency of extreme environmental events, potentially as a manifestation of global environmental change. There is a widely held belief that this trend could be linked with a future rise in the migration or displacement of human populations. However, recent approaches to migration influenced by environmental change call into question the notion that migration can be ascribed in a singular way to particular environmental causes or events. This paper undertakes a systematic review of evidence on population movements associated with weather-related extreme events. The paper demonstrates that in the face of extreme environmental events, it is important to distinguish between three outcomes – migration, displacement, and immobility – each of which interact and respond to multiple drivers. It also proposes a further insight: that both those who move, and those who do not move, may find themselves trapped and vulnerable in the face of such extreme events. A review of evidence suggests that short-term displacement that goes hand-in-hand with loss of life, destruction of property and economic disruption poses significant risks not because it is ‘environmental migration’, but because it represents a failure of adaptation to environmental change.