Mapping the landscape of the lymphocytic choriomeningitis virus stable signal peptide reveals novel functional domains

The stable signal peptide (SSP) of the lymphocytic choriomeningitis virus surface glycoprotein precursor has several unique characteristics. The SSP is unusually long, at 58 amino acids, and contains two hydrophobic domains, and its sequence is highly conserved among both Old and New World arenaviruses. To better understand the functions of the SSP, a panel of point and deletion mutants was created by in vitro mutagenesis to target the highly conserved elements within the SSP. We were also able to confirm critical residues required for separate SSP functions by trans-complementation. Using these approaches, it was possible to resolve functional domains of the SSP. In characterizing our SSP mutants, we discovered that the SSP is involved in several distinct functions within the viral life cycle, beyond translocation of the viral surface glycoprotein precursor into the endoplasmic reticulum lumen. The SSP is required for efficient glycoprotein expression, posttranslational maturation cleavage of GP1 and GP2 by SKI-1/S1P protease, glycoprotein transport to the cell surface plasma membrane, formation of infectious virus particles, and acid pH-dependent glycoprotein-mediated cell fusion.

Mapping CD55 function: the structure of two pathogen-binding domains at 1.7 A

Decay-accelerating factor (CD55), a regulator of the alternative and classical pathways of complement activation, is expressed on all serum-exposed cells. It is used by pathogens, including many enteroviruses and uropathogenic Escherichia coli, as a receptor prior to infection. We describe the x-ray structure of a pathogen-binding fragment of human CD55 at 1.7 A resolution containing two of the three domains required for regulation of human complement. We have used mutagenesis to map biological functions onto the molecule; decay-accelerating activity maps to a single face of the molecule, whereas bacterial and viral pathogens recognize a variety of different sites on CD55.

Mapping of domains on HIV envelope protein mediating association with calnexin and protein-disulfide isomerase.

The cell catalysts calnexin (CNX) and protein-disulfide isomerase (PDI) cooperate in establishing the disulfide bonding of the HIV envelope (Env) glycoprotein. Following HIV binding to lymphocytes, cell-surface PDI also reduces Env to induce the fusogenic conformation. We sought to define the contact points between Env and these catalysts to illustrate their potential as therapeutic targets. In lysates of Env-expressing cells, 15% of the gp160 precursor, but not gp120, coprecipitated with CNX, whereas only 0.25% of gp160 and gp120 coprecipitated with PDI. Under in vitro conditions, which mimic the Env/PDI interaction during virus/cell contact, PDI readily associated with Env. The domains of Env interacting in cellulo with CNX or in vitro with PDI were then determined using anti-Env antibodies whose binding site was occluded by CNX or PDI. Antibodies against domains V1/V2, C2, and the C terminus of V3 did not bind CNX-associated Env, whereas those against C1, V1/V2, and the CD4-binding domain did not react with PDI-associated Env. In addition, a mixture of the latter antibodies interfered with PDI-mediated Env reduction. Thus, Env interacts with intracellular CNX and extracellular PDI via discrete, largely nonoverlapping, regions. The sites of interaction explain the mode of action of compounds that target these two catalysts and may enable the design of further new competitive agents.

Boundary value problems for third-order linear PDEs in time-dependent domains

We present the extension of a methodology to solve moving boundary value problems from the second-order case to the case of the third-order linear evolution PDE qt + qxxx = 0. This extension is the crucial step needed to generalize this methodology to PDEs of arbitrary order. The methodology is based on the derivation of inversion formulae for a class of integral transforms that generalize the Fourier transform and on the analysis of the global relation associated with the PDE. The study of this relation and its inversion using the appropriate generalized transform are the main elements of the proof of our results.

Why we need new spectacles: Mapping the experiential dimension in prehistoric Cretan landscapes

The Bronze to Iron Age transition in Crete, a period of state collapse and insecurity, saw the island's rugged, high-contrast topography used in striking new ways. The visual drama of many of the new site locations has stimulated significant research over the last hundred years, with explanation of the change as the main focus. The new sites are not monumental in character: the vast majority are settlements, and much of the information about them comes from survey. Perhaps as a result, the new site map has not been much studied from phenomenological perspectives. A focus on the visual and experiential aspects of the new landscape can offer valuable insights into social structures at this period, and illuminate social developments prefiguring the emergence of polis states in Crete by c. 700 BC. To develop, share and evaluate this type of integrated study, digital reconstructive techniques are still under-used in this region. I highlight their potential value in addressing a regularly-identified shortcoming of phenomenological approaches-their necessarily subjective emphasis.

Geochemical mapping of carbonate sediments in the Makgadikgadi basin, Botswana using moderate resolution remote sensing data

This paper maps the carbonate geochemistry of the Makgadikgadi Pans region of northern Botswana from moderate resolution (500 m pixels) remotely sensed data, to assess the impact of various geomorphological processes on surficial carbonate distribution. Previous palaeo-environmental studies have demonstrated that the pans have experienced several highstands during the Quaternary, forming calcretes around shoreline embayments. The pans are also a significant regional source of dust, and some workers have suggested that surficial carbonate distributions may be controlled, in part, by wind regime. Field studies of carbonate deposits in the region have also highlighted the importance of fluvial and groundwater processes in calcrete formation. However, due to the large area involved and problems of accessibility, the carbonate distribution across the entire Makgadikgadi basin remains poorly understood. The MODIS instrument permits mapping of carbonate distribution over large areas; comparison with estimates from Landsat Thematic Mapper data show reasonable agreement, and there is good agreement with estimates from laboratory analysis of field samples. The results suggest that palaeo-lake highstands, reconstructed here using the SRTM 3 arc-second digital elevation model, have left behind surficial carbonate deposits, which can be mapped by the MODIS instrument. Copyright (c) 2006 John Wiley & Sons, Ltd.

Mapping the spatial distribution of geomorphological processes in the Okstindan area of northern Norway, using Geomorphic Process Units as derived from remote sensing and ground survey

The delineation of Geomorphic Process Units (GPUs) aims to quantify past, current and future geomorphological processes and the sediment flux associated with them. Five GPUs have been identified for the Okstindan area of northern Norway and these were derived from the combination of Landsat satellite imagery (TM and ETM+) with stereo aerial photographs (used to construct a Digital Elevation Model) and ground survey. The Okstindan study area is sub-arctic and mountainous and is dominated by glacial and periglacial processes. The GPUs exclude the glacial system (some 37% of the study area) and hence they are focussed upon periglacial and colluvial processes. The identified GPUs are: 1. solifluction and rill erosion; 2. talus creep, slope wash and rill erosion; 3. accumulation of debris by rock and boulder fall; 4. rockwalls; and 5. stable ground with dissolved transport. The GPUs have been applied to a ‘test site’ within the study area in order to illustrate their potential for mapping the spatial distribution of geomorphological processes. The test site within the study area is a catchment which is representative of the range of geomorphological processes identified.

Predictive vegetation mapping in the Mediterranean context: Considerations and methodological issues

The need to map vegetation communities over large areas for nature conservation and to predict the impact of environmental change on vegetation distributions, has stimulated the development of techniques for predictive vegetation mapping. Predictive vegetation studies start with the development of a model relating vegetation units and mapped physical data, followed by the application of that model to a geographic database and over a wide range of spatial scales. This field is particularly important for identifying sites for rare and endangered species and locations of high biodiversity such as many areas of the Mediterranean Basin. The potential of the approach is illustrated with a mapping exercise in the alti-meditterranean zone of Lefka Ori in Crete. The study established the nature of the relationship between vegetation communities and physical data including altitude, slope and geomorphology. In this way the knowledge of community distribution was improved enabling a GIS-based model capable of predicting community distribution to be constructed. The paper describes the development of the spatial model and the methodological problems of predictive mapping for monitoring Mediterranean ecosystems. The paper concludes with a discussion of the role of predictive vegetation mapping and other spatial techniques, such as fuzzy mapping and geostatistics, for improving our understanding of the dynamics of Mediterranean ecosystems and for practical management in a region that is under increasing pressure from human impact.

Why we need new spectacles: Mapping the experiential dimension in prehistoric Cretan landscapes

The Bronze to Iron Age transition in Crete, a period of state collapse and insecurity, saw the island's rugged, high-contrast topography used in striking new ways. The visual drama of many of the new site locations has stimulated significant research over the last hundred years, with explanation of the change as the main focus. The new sites are not monumental in character: the vast majority are settlements, and much of the information about them comes from survey. Perhaps as a result, the new site map has not been much studied from phenomenological perspectives. A focus on the visual and experiential aspects of the new landscape can offer valuable insights into social structures at this period, and illuminate social developments prefiguring the emergence of polis states in Crete by c. 700 BC. To develop, share and evaluate this type of integrated study, digital reconstructive techniques are still under-used in this region. I highlight their potential value in addressing a regularly-identified shortcoming of phenomenological approaches-their necessarily subjective emphasis.

Geochemical mapping of carbonate sediments in the Makgadikgadi basin, Botswana using moderate resolution remote sensing data

This paper maps the carbonate geochemistry of the Makgadikgadi Pans region of northern Botswana from moderate resolution (500 m pixels) remotely sensed data, to assess the impact of various geomorphological processes on surficial carbonate distribution. Previous palaeo-environmental studies have demonstrated that the pans have experienced several highstands during the Quaternary, forming calcretes around shoreline embayments. The pans are also a significant regional source of dust, and some workers have suggested that surficial carbonate distributions may be controlled, in part, by wind regime. Field studies of carbonate deposits in the region have also highlighted the importance of fluvial and groundwater processes in calcrete formation. However, due to the large area involved and problems of accessibility, the carbonate distribution across the entire Makgadikgadi basin remains poorly understood. The MODIS instrument permits mapping of carbonate distribution over large areas; comparison with estimates from Landsat Thematic Mapper data show reasonable agreement, and there is good agreement with estimates from laboratory analysis of field samples. The results suggest that palaeo-lake highstands, reconstructed here using the SRTM 3 arc-second digital elevation model, have left behind surficial carbonate deposits, which can be mapped by the MODIS instrument. Copyright (c) 2006 John Wiley & Sons, Ltd.

Use of a portable topographic mapping millimetre wave radar at an active lava flow

A ground-based millimetre wave radar, AVTIS (All-weather Volcano Topography Imaging Sensor), has been developed for topographic monitoring. The instrument is portable and capable of measurements over ranges up to similar to 7 km through cloud and at night. In April and May 2005, AVTIS was deployed at Arenal Volcano, Costa Rica, in order to determine topographic changes associated with the advance of a lava flow. This is the first reported application of mm-wave radar technology to the measurement of lava flux rates. Three topographic data sets of the flow were acquired from observation distances of similar to 3 km over an eight day period, during which the flow front was detected to have advanced similar to 200 m. Topographic differences between the data sets indicated a flow thickness of similar to 10 m, and a dense rock equivalent lava flux of similar to 0.20 +/- 0.08 m(3) s(-1).

Approximations to the scattering of water waves by steep topography

A new method is developed for approximating the scattering of linear surface gravity waves on water of varying quiescent depth in two dimensions. A conformal mapping of the fluid domain onto a uniform rectangular strip transforms steep and discontinuous bed profiles into relatively slowly varying, smooth functions in the transformed free-surface condition. By analogy with the mild-slope approach used extensively in unmapped domains, an approximate solution of the transformed problem is sought in the form of a modulated propagating wave which is determined by solving a second-order ordinary differential equation. This can be achieved numerically, but an analytic solution in the form of a rapidly convergent infinite series is also derived and provides simple explicit formulae for the scattered wave amplitudes. Small-amplitude and slow variations in the bedform that are excluded from the mapping procedure are incorporated in the approximation by a straightforward extension of the theory. The error incurred in using the method is established by means of a rigorous numerical investigation and it is found that remarkably accurate estimates of the scattered wave amplitudes are given for a wide range of bedforms and frequencies.