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.

Mechanisms of internalization and recycling of the chemokine receptor, CCR5

CCR5 is a G protein-coupled receptor that binds several natural chemokines but it is also a coreceptor for the entry of M tropic strains of HIV-1 into cells. Levels of CCR5 on the cell surface are important for the rate of HIV-1 infection and are determined by a number of factors including the rates of CCR5 internalization and recycling. Here we investigated the involvement of the actin cytoskeleton in the control of ligand-induced internalization and recycling of CCR5. Cytochalasin D, an actin depolymerizing agent, inhibited chemokine-induced internalization of CCR5 and recycling of the receptor in stably transfected CHO cells and in the monocytic cell line, THP-1. CCR5 internalization and recycling were inhibited by Toxin B and C-3 exoenzyme treatment in CHO and THP-1 cells, confirming activation of members of the RhoGTPase family by CCR5. The specific Rho kinase inhibitor Y27632, however, had no effect on CCR5 internalization or recycling. Ligand-induced activation of CCR5 leads to Rho kinase-dependent formation of focal adhesion complexes. These data indicate that CCR5 internalization and recycling are regulated by actin polymerization and activation of small G proteins in a Rho-dependent manner.

Solid-phase synthesis of an A-B loop mimetic of the C epsilon 3 domain of human IgE: macrocyclization by Sonogashira coupling

The solid-phase synthesis of a cyclic peptide containing the 21-residue epitope found in the A-B loop of the Cepsilon3 domain of human immunoglobulin E has been carried out. The key macrocyclization step to form the 65-membered ring is achieved in similar to15% yield via an "on-resin" Sonogashira coupling reaction which concomitantly installs a diphenylacetylene amino acid conformational constraint within the loop.

Lessons learnt about water use, harvesting, recycling and drainage

This Information Paper is the third in a four-part series that looks at the lessons learnt from the BRE Innovation Park concerning compliance with the Code for Sustainable Homes published in November 2006. It focuses on water use, harvesting, recycling and drainage. The other parts deal with: building fabric; energy sources, overheating and ventilation; architecture, construction and sourcing.

Evolving features-algorithms knowledge map to support NIDS data intelligence and learning loop architecting – a generalised approach to NIDS pattern feature space knowledge processing

This paper describes a proposed new approach to the Computer Network Security Intrusion Detection Systems (NIDS) application domain knowledge processing focused on a topic map technology-enabled representation of features of the threat pattern space as well as the knowledge of situated efficacy of alternative candidate algorithms for pattern recognition within the NIDS domain. Thus an integrative knowledge representation framework for virtualisation, data intelligence and learning loop architecting in the NIDS domain is described together with specific aspects of its deployment.

Optimising the feedback loop of a millimetre-wave absolute photoacoustic power meter using H-infinity control synthesis

An H-infinity control strategy has been developed for the design of controllers used in feedback controlled electrical substitution measurements (FCESM). The methodology has the potential to provide substantial improvements in both response time and resolution of a millimetre-wave absolute photoacoustic power meter.

Closed form approximations for spread options

This article expresses the price of a spread option as the sum of the prices of two compound options. One compound option is to exchange vanilla call options on the two underlying assets and the other is to exchange the corresponding put options. This way we derive a new closed form approximation for the price of a European spread option and a corresponding approximation for each of its price, volatility and correlation hedge ratios. Our approach has many advantages over existing analytical approximations, which have limited validity and an indeterminacy that renders them of little practical use. The compound exchange option approximation for European spread options is then extended to American spread options on assets that pay dividends or incur costs. Simulations quantify the accuracy of our approach; we also present an empirical application to the American crack spread options that are traded on NYMEX. For illustration, we compare our results with those obtained using the approximation attributed to Kirk (1996, Correlation in energy markets. In: V. Kaminski (Ed.), Managing Energy Price Risk, pp. 71–78 (London: Risk Publications)), which is commonly used by traders.

The role of closed ecological systems in carbon cycle modelling

Acquiring a mechanistic understanding of the role of the biotic feedbacks on the links between atmospheric CO2 concentrations and temperature is essential for trustworthy climate predictions. Currently, computer based simulations are the only available tool to estimate the global impact of the biotic feedbacks on future atmospheric CO2 and temperatures. Here we propose an alternative and complementary approaches by using materially closed and energetically open analogue/physical models of the carbon cycle. We argue that there is potential in using a materially closed approach to improve our understanding of the magnitude and sign of many biotic feedbacks, and that recent technological advance make this feasible. We also suggest how such systems could be designed and discuss the advantages and limitations of establishing physical models of the global carbon cycle.

Spatial and temporal effects of free-air CO2 enrichment (POPFACE) on leaf growth, cell expansion and cell production in a closed canopy of poplar

Leaf expansion in the fast-growing tree,Populus × euramericana was stimulated by elevated [CO2] in a closed-canopy forest plantation, exposed using a free air CO2 enrichment technique enabling long-term experimentation in field conditions. The effects of elevated [CO2] over time were characterized and related to the leaf plastochron index (LPI), and showed that leaf expansion was stimulated at very early (LPI, 0–3) and late (LPI, 6–8) stages in development. Early and late effects of elevated [CO2] were largely the result of increased cell expansion and increased cell production, respectively. Spatial effects of elevated [CO2] were also marked and increased final leaf size resulted from an effect on leaf area, but not leaf length, demonstrating changed leaf shape in response to [CO2]. Leaves exhibited a basipetal gradient of leaf development, investigated by defining seven interveinal areas, with growth ceasing first at the leaf tip. Interestingly, and in contrast to other reports, no spatial differences in epidermal cell size were apparent across the lamina, whereas a clear basipetal gradient in cell production rate was found. These data suggest that the rate and timing of cell production was more important in determining leaf shape, given the constant cell size across the leaf lamina. The effect of elevated [CO2] imposed on this developmental gradient suggested that leaf cell production continued longer in elevated [CO2] and that basal increases in cell production rate were also more important than altered cell expansion for increased final leaf size and altered leaf shape in elevated [CO2].

Interchange reconnection: remote sensing of solar signature and role in heliospheric magnetic flux budget

Interchange reconnection at the Sun, that is, reconnection between a doubly-connected field loop and singly-connected or open field line that extends to infinity, has important implications for the heliospheric magnetic flux budget. Recent work on the topic is reviewed, with emphasis on two aspects. The first is a possible heliospheric signature of interchange reconnection at the coronal hole boundary, where open fields meet closed loops. The second aspect concerns the means by which the heliospheric magnetic field strength reached record-lows during the recent solar minimum period. A new implication of this work is that interchange reconnection may be responsible for the puzzling, occasional coincidence of the heliospheric current sheet and the interface between fast and slow flow in the solar wind.

Value management and post-occupancy evaluation: closing the loop

This paper considers the relationship between value management and facilities management. The findings are particularly relevant to large client organisations which procure new buildings on a regular basis. It is argued that the maximum effectiveness of value management can only be achieved if it is used in conjunction with an ongoing commitment to post-occupancy evaluation. SMART value management is seen to provide the means of ensuring that an individual building design is in alignment with the client’s strategic property needs. However, it is also necessary to recognise that an organisation’s strategic property needs will continually be in a state of change. Consequentially, economic and functional under-performance can only be avoided by a regular performance audit of existing property stock in accordance with changing requirements. Such a policy will ensure ongoing competitiveness through organisational learning. While post-occupancy evaluation represents an obvious additional service to be provided by value management consultants, it is vital that the necessary additional skills are acquired. Process management skills and social science research techniques are clearly important. However, there is also a need to improve mechanisms for data manipulation. Success can only be achieved if equal attention is given to issues of process, structure and content.

A closed paramagnetic electron-precise cluster

A pentametallic cluster is formed by addition of two [SnR2][R = CH(SiMe3)2] groups to [Os3(CO)8(µ-H)(C6H4PhPCH2PPh2)], in a reaction reversing the ortho-hydrogen abstraction and giving the first closed electron-precise paramagnetic cluster.

Open and closed edges of graphene layers

Edge structures of thermally treated graphite have been studied by means of atomically resolved high-resolution TEM. The method for the determination of a monolayer or more than one layer graphene sheets is established. A series of tilting experiments proves that the zigzag and armchair edges are mostly closed between adjacent graphene layers, and the number of dangling bonds is therefore minimized. Surprisingly bilayer graphene often exhibits AA stacking and is very hard to distinguish from a single graphene layer. Open edge structures with carbon dangling bonds can be found only in a local area where the closed (folding) edge is partially broken.