LiDAR mapping of tidal marshes for ecogeomorphological modelling in the TIDE project

The European research project TIDE (Tidal Inlets Dynamics and Environment) is developing and validating coupled models describing the morphological, biological and ecological evolution of tidal environments. The interactions between the physical and biological processes occurring in these regions requires that the system be studied as a whole rather than as separate parts. Extensive use of remote sensing including LiDAR is being made to provide validation data for the modelling. This paper describes the different uses of LiDAR within the project and their relevance to the TIDE science objectives. LiDAR data have been acquired from three different environments, the Venice Lagoon in Italy, Morecambe Bay in England, and the Eden estuary in Scotland. LiDAR accuracy at each site has been evaluated using ground reference data acquired with differential GPS. A semi-automatic technique has been developed to extract tidal channel networks from LiDAR data either used alone or fused with aerial photography. While the resulting networks may require some correction, the procedure does allow network extraction over large areas using objective criteria and reduces fieldwork requirements. The networks extracted may subsequently be used in geomorphological analyses, for example to describe the drainage patterns induced by networks and to examine the rate of change of networks. Estimation of the heights of the low and sparse vegetation on marshes is being investigated by analysis of the statistical distribution of the measured LiDAR heights. Species having different mean heights may be separated using the first-order moments of the height distribution.

System dynamics mapping of acute patient flows

Department of Health staff wished to use systems modelling to discuss acute patient flows with groups of NHS staff. The aim was to assess the usefulness of system dynamics (SD) in a healthcare context and to elicit proposals concerning ways of improving patient experience. Since time restrictions excluded simulation modelling, a hybrid approach using stock/flow symbols from SD was created. Initial interviews and hospital site visits generated a series of stock/flow maps. A ‘Conceptual Framework’ was then created to introduce the mapping symbols and to generate a series of questions about different patient paths and what might speed or slow patient flows. These materials formed the centre of three workshops for NHS staff. The participants were able to propose ideas for improving patient flows and the elicited data was subsequently employed to create a finalized suite of maps of a general acute hospital. The maps and ideas were communicated back to the Department of Health and subsequently assisted the work of the Modernization Agency.

A change detection approach to flood mapping in urban areas using TerraSAR-X

Very high-resolution Synthetic Aperture Radar sensors represent an alternative to aerial photography for delineating floods in built-up environments where flood risk is highest. However, even with currently available SAR image resolutions of 3 m and higher, signal returns from man-made structures hamper the accurate mapping of flooded areas. Enhanced image processing algorithms and a better exploitation of image archives are required to facilitate the use of microwave remote sensing data for monitoring flood dynamics in urban areas. In this study a hybrid methodology combining radiometric thresholding, region growing and change detection is introduced as an approach enabling the automated, objective and reliable flood extent extraction from very high-resolution urban SAR images. The method is based on the calibration of a statistical distribution of “open water” backscatter values inferred from SAR images of floods. SAR images acquired during dry conditions enable the identification of areas i) that are not “visible” to the sensor (i.e. regions affected by ‘layover’ and ‘shadow’) and ii) that systematically behave as specular reflectors (e.g. smooth tarmac, permanent water bodies). Change detection with respect to a pre- or post flood reference image thereby reduces over-detection of inundated areas. A case study of the July 2007 Severn River flood (UK) observed by the very high-resolution SAR sensor on board TerraSAR-X as well as airborne photography highlights advantages and limitations of the proposed method. We conclude that even though the fully automated SAR-based flood mapping technique overcomes some limitations of previous methods, further technological and methodological improvements are necessary for SAR-based flood detection in urban areas to match the flood mapping capability of high quality aerial photography.

Extraction of tidal channel networks from aerial photographs alone and combined with laser altimetry

Tidal channel networks play an important role in the intertidal zone, exerting substantial control over the hydrodynamics and sediment transport of the region and hence over the evolution of the salt marshes and tidal flats. The study of the morphodynamics of tidal channels is currently an active area of research, and a number of theories have been proposed which require for their validation measurement of channels over extensive areas. Remotely sensed data provide a suitable means for such channel mapping. The paper describes a technique that may be adapted to extract tidal channels from either aerial photographs or LiDAR data separately, or from both types of data used together in a fusion approach. Application of the technique to channel extraction from LiDAR data has been described previously. However, aerial photographs of intertidal zones are much more commonly available than LiDAR data, and most LiDAR flights now involve acquisition of multispectral images to complement the LiDAR data. In view of this, the paper investigates the use of multispectral data for semiautomatic identification of tidal channels, firstly from only aerial photographs or linescanner data, and secondly from fused linescanner and LiDAR data sets. A multi-level, knowledge-based approach is employed. The algorithm based on aerial photography can achieve a useful channel extraction, though may fail to detect some of the smaller channels, partly because the spectral response of parts of the non-channel areas may be similar to that of the channels. The algorithm for channel extraction from fused LiDAR and spectral data gives an increased accuracy, though only slightly higher than that obtained using LiDAR data alone. The results illustrate the difficulty of developing a fully automated method, and justify the semi-automatic approach adopted.

A conserved basic loop in hepatitis C virus p7 protein is required for amantadine-sensitive ion channel activity in mammalian cells but is dispensable for localization to mitochondria

We previously identified the function of the hepatitis C virus (HCV) p7 protein as an ion channel in artificial lipid bilayers and demonstrated that this in vitro activity is inhibited by amantadine. Here we show that the ion channel activity of HCV p7 expressed in mammalian cells can substitute for that of influenza virus M2 in a cell-based assay. This was also the case for the p7 from the related virus, bovine viral diarrhoea virus (BVDV). Moreover, amantadine was shown to abrogate HCV p7 function in this assay at a concentration that specifically inhibits M2. Mutation of a conserved basic loop located between the two predicted trans-membrane alpha helices rendered HCV p7 non-functional as an ion channel. The intracellular localization of p7 was unaffected by this mutation and was found to overlap significantly with membranes associated with mitochondria. Demonstration of p7 ion channel activity in cellular membranes and its inhibition by amantadine affirm the protein as a target for future anti-viral chemotherapy.

Mapping antimalarial pharmacophores as a useful tool for the rapid discovery of drugs effective in vivo: design, construction, characterization, and pharmacology of metaquine

Resistant strains of Plasmodium falciparum and the unavailability of useful antimalarial vaccines reinforce the need to develop new efficacious antimalarials. This study details a pharmacophore model that has been used to identify a potent, soluble, orally bioavailable antimalarial bisquinoline, metaquine (N,N'-bis(7-chloroquinolin-4-yl)benzene-1,3-diamine) (dihydrochloride), which is active against Plasmodium berghei in vivo (oral ID50 of 25 mu mol/kg) and multidrug-resistant Plasmodium falciparum K1 in vitro (0.17 mu M). Metaquine shows strong affinity for the putative antimalarial receptor, heme at pH 7.4 in aqueous DMSO. Both crystallographic analyses and quantum mechanical calculations (HF/6-31+G*) reveal important regions of protonation and bonding thought to persist at parasitic vacuolar pH concordant with our receptor model. Formation of drug-heme adduct in solution was confirmed using high-resolution positive ion electrospray mass spectrometry. Metaquine showed strong binding with the receptor in a 1: 1 ratio (log K = 5.7 +/- 0.1) that was predicted by molecular mechanics calculations. This study illustrates a rational multidisciplinary approach for the development of new 4-aminoquinoline antimalarials, with efficacy superior to chloroquine, based on the use of a pharmacophore model.

Enhanced hepatitis C virus genome replication and lipid accumulation mediated by inhibition of AMP-activated protein kinase

Hepatitis C virus (HCV) infection is associated with dysregulation of both lipid and glucose metabolism. As well as contributing to viral replication, these perturbations influence the pathogenesis associated with the virus, including steatosis, insulin resistance, and type 2 diabetes. AMP-activated protein kinase (AMPK) plays a key role in regulation of both lipid and glucose metabolism. We show here that, in cells either infected with HCV or harboring an HCV subgenomic replicon, phosphorylation of AMPK at threonine 172 and concomitant AMPK activity are dramatically reduced. We demonstrate that this effect is mediated by activation of the serine/threonine kinase, protein kinase B, which inhibits AMPK by phosphorylating serine 485. The physiological significance of this inhibition is demonstrated by the observation that pharmacological restoration of AMPK activity not only abrogates the lipid accumulation observed in virus-infected and subgenomic replicon-harboring cells but also efficiently inhibits viral replication. These data demonstrate that inhibition of AMPK is required for HCV replication and that the restoration of AMPK activity may present a target for much needed anti-HCV therapies.

Suppression of a pro-apoptotic K+ channel as a mechanism for hepatitis C virus persistence

An estimated 3% of the global population are infected with hepatitis C virus (HCV), and the majority of these individuals will develop chronic liver disease. As with other chronic viruses, establishment of persistent infection requires that HCV-infected cells must be refractory to a range of pro-apoptotic stimuli. In response to oxidative stress, amplification of an outward K(+) current mediated by the Kv2.1 channel, precedes the onset of apoptosis. We show here that in human hepatoma cells either infected with HCV or harboring an HCV subgenomic replicon, oxidative stress failed to initiate apoptosis via Kv2.1. The HCV NS5A protein mediated this effect by inhibiting oxidative stress-induced p38 MAPK phosphorylation of Kv2.1. The inhibition of a host cell K(+) channel by a viral protein is a hitherto undescribed viral anti-apoptotic mechanism and represents a potential target for antiviral therapy.

Mapping the trickle out benefits of social and environmental enterprises: a pilot study of an East African eco business

• Objectives The objective of this paper is to propose a framework for mapping the sustainable development and poverty alleviation impacts of social and environmental enterprises in Africa. This framework is then piloted with reference to an East African Ecobusiness. • Prior Work This paper is based on data collected as part of a wider research project examining social and environmental enterprises across the 19 countries of Southern and Eastern Africa. In total, the sustainable development and poverty alleviation impacts of 20 in-depth case studies in 4 countries are being examined. • Approach Data was collected using in-depth interviews with multiple stakeholders associated with the case study business. Secondary materials were also analysed and a quantitative survey of customers undertaken. • Results In addition to their impacts on the environment, African eco businesses can also have substantial social, economic and wider poverty alleviation impacts. This paper maps the impacts of a case study East African ecobusiness, as part of developing a social and environmental enterprise impact framework for Africa and the wider developing world. In our case study, positive and negative impacts are identified, while questions are raised in relation to tradeoffs between social and environmental objectives and temporal dimensions of impact. The usefulness of existing frameworks for understanding the social, environmental and development impacts of these kinds of organisations are also considered. • Implications This paper outlines the necessity of building an African-centric impact map to capture the multi-level poverty alleviation and sustainable development impacts of social and environmental enterprise activity in developing world environments. The framework proposed also offers guidance to businesses operating in Africa about the factors that might be considered as part of their wider social and environmental responsibilities. • Value Assessing the impact of social and environmental enterprises, especially as a route to development within low income countries, is receiving increasing attention in academia and beyond. This paper presents a useful contribution to the scarce literature on social and environmental enterprises in Africa.

Modeling growth strategy in a biotechnology startup firm

The top managers of a biotechnology startup firm agreed to participate in a system dynamics modeling project to help them think about the firm's growth strategy. The article describes how the model was created and used to stimulate debate and discussion about growth management. The paper highlights several novel features about the process used for capturing management team knowledge. A heavy emphasis was placed on mapping the operating structure of the factory and distribution channels. Qualitative modeling methods (structural diagrams, descriptive variable names, and friendly algebra) were used to capture the management team's descriptions of the business. Simulation scenarios were crafted to stimulate debate about strategic issues such as capacity allocation, capacity expansion, customer recruitment, customer retention, and market growth, and to engage the management team in using the computer to design strategic scenarios. The article concludes with comments on the impact of the project.

The permeability parameter of the outer membrane of pseudomonas aeruginosa Varies with the concentration of a test substrate, cephalosporin C

The permeability parameter (C) for the movement of cephalosporin C across the outer membrane of Pseudomonas aeruginosa was measured using the widely accepted method of Zimmermann & Rosselet. In one experiment, the value of C varied continuously from 4·2 to 10·8 cm3 min-1 (mg dry wt cells)-1 over a range of concentrations of the test substrate, cephalosporin C, from 50 to 5 μm. Dependence of C on the concentration of test substrate was still observed when the effect of a possible electric potential difference across the outer membrane was corrected for. In quantitative studies of β-lactam permeation the dependence of C on the concentration of β-lactam should be taken into account.