Role of conformational constraints of position 7 of the disulphide bridge of h-alpha-CGRP derivatives in their agonist versus antagonist properties

Previous structure-activity studies have shown that the disulphide bridge of calcitonin gene-related peptide (CGRP) is important for the highly potent, CGRP receptor-mediated effects of this peptide. In this study penicillamine (Pen) was substituted for one or both of the cysteinyl residues to determine conformational and topographical properties of the disulphide bridge favourable for binding to CGRP receptors and/or receptor activation. Pen constrains the conformational flexibility of disulphide bridges in other peptides. Binding affinities were measured using a radioligand binding assay with membranes prepared from pig coronary arteries and I-125-h-alpha-CGRP. Functional effects were characterized using a previously reported pig coronary artery relaxation bioassay. The binding affinity of [Pen(2)]h-alpha-CGRP was not significantly different from that of h-alpha-CGRP. All other analogues showed reduced affinity for CGRP receptors. [Pen(2)]h-alpha-CGRP also caused relaxation of coronary arteries. The remaining analogues either caused relaxation with significantly reduced potency or failed to relax the arteries at concentrations up to 1 x 10(-5) M. All analogues that did not relax coronary arteries contained a D-Pen in position 7 and inhibited CGRP-induced relaxation. [D-Pen(2,7)]h-alpha- CGRP was the most potent antagonist with a K-B value of 630 nM. This affinity is similar to that of the classical CGRP receptor antagonist, h-alpha-CGRP(8-37), on these arteries (K-B, 212 nM). These studies show that modifying the topography of the disulphide bridge can cause large and variable effects on ligand binding and activation of CGRP receptors. The contribution of position 7 to the conformation and topography of the disulphide bridge of h-alpha-CGRP is crucial to the future design of agonists of CGRP receptors. Furthermore, position 7 is important for the development of new CGRP receptor antagonists with structures based on the whole sequence of h-alpha-CGRP.

The distribution of Fasciola hepatica and Fasciola gigantica within southern Tanzania - constraints associated with the intermediate host

In East Africa, Fasciola gigantica is generally the causative agent of fasciolosis but there have been reports of F. hepatica in cattle from highland regions of Kenya, Ethiopia, Uganda and Zaire. The topography of the Southern Highlands of Tanzania provides an environment where the climatic conditions exist for the sustenance of lymnaeid species capable of Supporting both Fasciola hepatica and F. gigantica. Theoretically this would allow interaction between fasciolid species and the possible creation of hybrids. In this report we present molecular data confirming the existence of the snail, Lymnaea truncatula, at high altitude on the Kitulo Plateau of the Southern Highlands, Tanzania, along with morphometric and molecular data confirming the presence of F. hepatica in the corresponding area. At lower altitudes, where climatic conditions were unfavourable for the existence of L. truncatula, the presence of its sister species L. natalensis was confirmed by molecular data along with its preferred fasciolid parasite, F. gigantica. Analysis based on a 618 bp sequence of the 28S rRNA gene did not reveal the presence of hybrid fasciolids in our fluke samples.

Designs and designers of medieval ‘new towns’ in Wales

Medieval 'new towns' seem to echo Roman towns in having a grid of streets associated with a fortress, and have often been credited with a standard plan applied by the hand of authority. Here the authors analyse the new towns founded by Edward I in Wales and find some highly significant variations. Rediscovering the original layouts by high precision survey and GIS mapping, they show that some towns, founded at the same time and on similar topography, had quite different layouts, while others, founded at long intervals, had plans that were almost identical. Documentation hints at the explanation: it was the architects, masons and ditch-diggers, not the king and aristocracy, who established and developed these blueprints of urban life.

Sub-fossil Insects and ecosystem dynamics in wetlands; implications for biodiversity and conservation.

We review the uses of fossil insects, particularly Coleoptera (beetles) and Chironomidae (non-biting midges) from ancient deposits to inform the study of wetland ecosystems and their ecological and restoration processes. In particular, we focus on two contrasting ecosystems, drawing upon research undertaken by us on British raised mire peats and shallow lake systems, one an essentially terrestrial ecosystem, the other aquatic, but in which wetland insects play an important and integral part. The study of raised mire peats suggests that faunal stability is a characteristic of these wetland systems, over what appear to be extensive periods of time (up to several millennia), whilst studies of shallow lake ecosystems over recent timescales indicates that faunal instability appears to be more common, usually driven by increasing eutrophication. Drawing upon a series of fossil Coleoptera records spanning several thousand years from Hatfield Moors, south Yorkshire, we reconstruct in some detail the mire’s ontogeny and fluctuations in site hydrology and vegetation cover, illustrating the intimate association between substrate, topography and peat development. A comparison between fossil and modern beetle populations indicates that the faunal characteristics of this mire and its adjacent neighbour, Thorne Moors, become established during the early phases of peat development, including its rare endemics, and that the faunal biodiversity on the sites today is dictated by complex site histories. The over-riding characteristic of these faunas is of stability over several thousand years, which has important implications for the restoration of degraded sites, especially those where refugial areas are limited. In contrast, analyses of fossil Chironomidae from shallow lakes allow researchers to track changes in limnological status and while attempts have been made to reconstruct changes in nutrient levels quantitatively, the chironomids respond indirectly to such changes, typically mediated through complex ecosystem dynamics such as changes in fish and/or macrophyte communities. These changes are illustrated via historic chironomid stratigraphies and diversity indices from a range of shallow lakes located across Britain: Slapton Ley, Frensham Great Pond, Fleet Pond, Kyre Pool and Barnes Loch. These sites have shown varying degrees of eutrophication over recent timescales which tends to be associated with a decline in chironomid diversity. While complex functional processes exist within these ecosystems, our evidence suggests that one of the key drivers in the loss of shallow lake chironomid diversity appears to be the loss of aquatic macrophytes. Overall, while chironomids do show a clear response to altered nutrient regimes, multi-proxy reconstructions are recommended for a clear interpretation of past change. We conclude that if we are to have a better understanding of biota at the ecosystem level we need to know more of the complex interactions between different insect groups as well as with other animal and plant communities. A palaeoecological approach is thus crucial in order to assess the role of insect groups in ecosystem processes, both in the recent past and over long time scales, and is essential for wetland managers and conservation organisations involved in long term management and restoration of wetland systems.

Echinostoma caproni: Differential tegumental responses to growth in compatible and less compatible hosts

The topography of the tegument of Echinostoma caproni adults collected from high (mice) and low (rats) compatible hosts was compared by SEM. In the oral (OS) and the ventral sucker (VS) areas, a worm age-host species interaction was found with regard to the density of spines. There was a decrease in the density of spines in the adults collected from mice, whereas an increase occurred in the OS area in worms from rats over time. The tegumentary spines in adults from mice became larger and blunter. Some spines from the VS area in adults from mice at 4 wpi were multipointed. The spines of adults from rats were sharper, not covered by the tegument and no multipointed spines were observed. We detected a greater level of actin gene expression in the adults collected from rats. These facts suggest that the low compatible host induces an increased turnover of tegumentary spines. (C) 2010 Elsevier Inc. All rights reserved.

Light emission from gold and silver thin films in a scanning tunneling microscope: role of contamination and interpretation of grain structure in photon maps

Scanning tunnelling microscope (STM) tip-induced light emission from Au and Ag has been studied. Thin film samples similar to100nm thick were prepared by thermal evaporation at 0.5nm/s onto a room-temperature glass substrate to produce grains of 20-50nm in lateral dimension at the surface. Light emission from the samples in the STM was quasi-simultaneously recorded with the topography, at 1.8V tip bias and 3-40nA current, alternating pixel by pixel at the same bias. Typically, a surface scan range of 150 nm x 150 nm was surveyed. Au, W and PtIr tips were used.

RAMAN-SCATTERING AND SCANNING ELECTRON-TUNNELING STUDIES OF METAL LIQUID-LIKE FILMS PRODUCED FROM SILVER AND GOLD SOLS

Surface-enhanced Raman scattering (SERS) excited at several visible wavelengths and recorded using a cooled charged-coupled device detector is reported from the mobile, interfacial, liquid-like metal films (MELLFs) formed when solutions of metal complexes or pyridine in chlorocarbon solvents are mixed with aqueous sols of silver or gold. MELLF formation has not previously been reported for gold sols or for pyridine as stabilizer. Comparison of the spectra for the MELLFs formed from individual metal complexes and from 50:50 mixtures show that the spectral patterns observed for the latter are distinctive and are not generally equivalent to the sum of the spectra associated with the individual complexes, in contrast to the situation observed for sols where the individual spectra do appear to be additive. Raman scattering from both gold and silver MELLFs is readily observed at excitation wavelengths in the red, around 750 nm, but at 514 nm only that from silver films is detectable. These findings are considered in terms of particle size and absorption band intensities. A preliminary study of the film surface topography and particle size was carried out by scanning tunnelling electron microscopy (STM) of Ag MELLFs deposited on gold-coated mica substrates. Computer-processed images of the STM data show the presence on the film surface of finger-like bars, 200-400 nm long with approximately square cross-section, 40-60 nm side, together with other smaller cuboid features. The implications of these findings in relation to SERS are briefly considered.

Hydraulic Subsurface Measurements and Hydrodynamic Modeling as Indicators for Groundwater Flow Systems in the Rotondo Granite, Central Alps (Switzerland)

Regional groundwater flow in high mountainous terrain is governed by a multitude of factors such as geology, topography, recharge conditions, structural elements such as fracturation and regional fault zones as well as man-made underground structures. By means of a numerical groundwater flow model, we consider the impact of deep underground tunnels and of an idealized major fault zone on the groundwater flow systems within the fractured Rotondo granite. The position of the free groundwater table as response to the above subsurface structures and, in particular, with regard to the influence of spatial distributed groundwater recharge rates is addressed. The model results show significant unsaturated zones below the mountain ridges in the study area with a thickness of up to several hundred metres. The subsurface galleries are shown to have a strong effect on the head distribution in the model domain, causing locally a reversal of natural head gradients. With respect to the position of the catchment areas to the tunnel and the corresponding type of recharge source for the tunnel inflows (i.e. glaciers or recent precipitation), as well as water table elevation, the influence of spatial distributed recharge rates is compared to uniform recharge rates. Water table elevations below the well exposed high-relief mountain ridges are observed to be more sensitive to changes in groundwater recharge rates and permeability than below ridges with less topographic relief. In the conceptual framework of the numerical simulations, the model fault zone has less influence on the groundwater table position, but more importantly acts as fast flow path for recharge from glaciated areas towards the subsurface galleries. This is in agreement with a previous study, where the imprint of glacial recharge was observed in the environmental isotope composition of groundwater sampled in the subsurface galleries. Copyright © 2012 John Wiley & Sons, Ltd.

Spanish Golden Age Poetry in Motion: The Dynamics of Creation and Conversation.

The fourteen essays of this volume engage in distinct ways with the matter of motion in early modern Spanish poetics, without limiting the dialectic of stasis and movement to any single sphere or manifestation. Interrogation of the interdependence of tradition and innovation, poetry, power and politics, shifting signifiers, the intersection of topography and deviant temporalities, the movement between the secular and the sacred, tensions between centres and peripheries, issues of manuscript circulation and reception, poetic calls and echoes across continents and centuries, and between creative writing and reading subjects, all demonstrate that Helgerson's central notion of conspicuous movement is relevant beyond early sixteenth-century secular poetics, By opening it up we approximate a better understanding of poetry's flexible spatio-temporal co-ordinates in a period of extraordinary historical circumstances and conterminous radical cultural transformation

Using the surface profiles of modern ice masses to inform palaeo-glacier reconstructions

Morphometric study of modern ice masses is useful because many reconstructions of glaciers traditionally draw on their shape for guidance Here we analyse data derived from the surface profiles of 200 modern ice masses-valley glaciers icefields ice caps and ice sheets with length scales from 10º to 10³ km-from different parts of the world Four profile attributes are investigated relief span and two parameters C* and C that result from using Nye s (1952) theoretical parabola as a profile descriptor C* and C respectively measure each profile s aspect ratio and steepness and are found to decrease in size and variability with span This dependence quantifies the competing influences of unconstrained spreading behaviour of ice flow and bed topography on the profile shape of ice masses which becomes more parabolic as span Increases (with C* and C tending to low values of 2.5-3.3 m ½) The same data reveal coherent minimum bounds in C* and C for modern ice masses that we develop into two new methods of palaeo glacier reconstruction In the first method glacial limits are known from moraines and the bounds are used to constrain the lowest palaeo ice surface consistent with modern profiles We give an example of applying this method over a three-dimensional glacial landscape in Kamchatka In the second method we test the plausibility of existing reconstructions by comparing their C* and C against the modern minimum bounds Of the 86 published palaeo ice masses that we put to this test 88% are found to be plausible The search for other morphometric constraints will help us formalise glacier reconstructions and reduce their uncertainty and subjectiveness

The analysis of large-scale turbulence characteristics in the Indonesian seas derived from a regional model based on the Princeton Ocean Model

Turbulence characteristics in the Indonesian seas on the horizontal scale of order of 100 km were calculated with a regional model of the Indonesian seas circulation in the area based on the Princeton Ocean Model (POM). As is well known, the POM incorporates the Mellor–Yamada turbulence closure scheme. The calculated characteristics are: twice the turbulence kinetic energy per unit mass, <i>q</i>²; the turbulence master scale, &ell;; mixing coefficients of momentum, <i>K</i>_M; and temperature and salinity, <i>K</i>_H; etc. The analyzed turbulence has been generated essentially by the shear of large-scale ocean currents and by the large-scale wind turbulence. We focused on the analysis of turbulence around important topographic features, such as the Lifamatola Sill, the North Sangihe Ridge, the Dewakang Sill, and the North and South Halmahera Sea Sills. In general, the structure of turbulence characteristics in these regions turned out to be similar. For this reason, we have carried out a detailed analysis of the Lifamatola Sill region because dynamically this region is very important and some estimates of mixing coefficients in this area are available. <br><br> Briefly, the main results are as follows. The distribution of <i>q</i>² is quite adequately reproduced by the model. To the north of the Lifamatola Sill (in the Maluku Sea) and to the south of the Sill (in the Seram Sea), large values of <i>q</i>² occur in the deep layer extending several hundred meters above the bottom. The observed increase of <i>q</i>² near the very bottom is probably due to the increase of velocity shear and the corresponding shear production of <i>q</i>² very close to the bottom. The turbulence master scale, &ell;, was found to be constant in the main depth of the ocean, while &ell; rapidly decreases close to the bottom, as one would expect. However, in deep profiles away from the sill, the effect of topography results in the &ell; structure being unreasonably complicated as one moves towards the bottom. Values of 15 to 20 × 10^&minus;4 m² s^-1 were obtained for <i>K</i>_M and <i>K</i>_H in deep water in the vicinity of the Lifamatola Sill. These estimates agree well with basin-scale averaged values of 13.3 × 10^&minus;4 m² s^-1 found diagnostically for <i>K</i>_H in the deep Banda and Seram Seas (Gordon et al., 2003) and a value of 9.0 × 10^&minus;4 m² s^-1 found diagnostically for <i>K</i>_H for the deep Banda Sea system (van Aken et al., 1988). The somewhat higher simulated values can be explained by the presence of steep topography around the sill.

Clara Bog: An ombotrophic groundwater dependant terrestrial ecosystem (Submitted)

Comparison of flow duration curves for a weir draining an undrained raised peat with those generated 20 years previously reveal that more recent curves reflect to be flatter with a lower Q95/Q5 ratio. Comparison of the bog topography for the same period revealed that although marginal drainage/peat reclamation had resulted in desiccation of peat around the bog margin and more frequent intense runoff, the central part of the bog had subsided to form an enclosed basin ,resulting in the creation of newly formed lakes that gave the central part of the bog an improved capacity to store, and more slowly discharge, water. Interrogation of groundwater monitoring data revealed a net decline in groundwater levels of up to three metres in the glacial tills underlying the bog associated with deepening and expansion of a marginal drain network which penetrated the base of the peat. Comparing organic carbon levels in peat the central part of the bog over a ten year period revealed an overall increase, with changes being most marked in deeper fen peat layers. These findings suggest that the decline in groundwater levels in the peat substrate resulted in an increase in effective stress in the peat causing greater subsidence in the central part of the bog due to greater overall thickness. Study results highlight how the hydrology of apparently isolated obotrophic raised bog ecosystems may be influenced by groundwater pressures in deeper deposits, and how marginal drains may have the capacity to impact areas at significant distances.

Rapid succession of plant associations on the small ocean island of Mauritius at the onset of the Holocene

The island of Mauritius offers the opportunity to study the poorly understood vegetation response to climate change on a small tropical oceanic island. A high-resolution pollen record from a 10 m long peat core from Kanaka Crater (560 m elevation, Mauritius, Indian Ocean) shows that vegetation shifted from a stable open wet forest Last Glacial state to a stable closed-stratified-tall-forest Holocene state. An ecological threshold was crossed at ∼11.5 cal ka BP, propelling the forest ecosystem into an unstable period lasting ∼4000 years. The shift between the two steady states involves a cascade of four abrupt (<150 years) forest transitions in which different tree species dominated the vegetation for a quasi-stable period of respectively ∼1900, ∼1100 and ∼900 years. We interpret the first forest transition as climate-driven, reflecting the response of a small low topography oceanic island where significant spatial biome migration is impossible. The three subsequent forest transitions are not evidently linked to climate events, and are suggested to be driven by internal forest dynamics. The cascade of four consecutive events of species turnover occurred at a remarkably fast rate compared to changes during the preceding and following periods, and might therefore be considered as a composite tipping point in the ecosystem. We hypothesize that wet gallery forest, spatially and temporally stabilized by the drainage system, served as a long lasting reservoir of biodiversity and facilitated a rapid exchange of species with the montane forests to allow for a rapid cascade of plant associations.

Introduction to Wireless Intrusion Detection Systems

The IDS (Intrusion Detection System) is a common means of protecting networked systems from attack or malicious misuse. The development and rollout of an IDS can take many different forms in terms of equipment, protocols, connectivity, cost and automation. This is particularly true of WIDS (Wireless Intrusion Detection Systems) which have many more opportunities and challenges associated with data transmission through an open, shared medium.
The operation of a WIDS is a multistep process from origination of an attack through to human readable evaluation. Attention to the performance of each of the processes in the chain from attack detection to evaluation is imperative if an optimum solution is to be sought. At present, research focuses very much on each discrete aspect of a WIDS with little consideration to the operation of the whole system. Taking a holistic view of the technology shows the interconnectivity and inter-dependence between stages, leading to improvements and novel research areas for investigation.
This chapter will outline the general structure of Wireless Intrusion Detection Systems and briefly describe the functions of each development stage, categorised into the following 6 areas:
• Threat Identification,
• Architecture,
• Data Collection,
• Intrusion Detection,
• Alert Correlation,
• Evaluation.
These topics will be considered in broad terms designed for those new to the area. Focus will be placed on ensuring the readers are aware of the impact of choices made at early stages in WIDS development on future stages.

Effects of short term increase of intraocular pressure on optic disc cupping

Aims. To evaluate the effect of acute elevation of intraocular pressure (IOP) on optic disc cupping. Methods. 10 emmetropic and 10 myopic volunteers were included in this study. The cup area (CA) and cup volume (CV) of the optic disc were determined with the Heidelberg retina tomograph (HRT). After baseline determinations, a suction cup was used to increase the intraocular pressure (IOP) to 20-25 mmHg above the baseline and HRT images were obtained. Results. Baseline IOP was 13.5 (SD 1.3) mmHg and 12.6 (2.6) mmHg in the emmetropic and myopic groups, respectively. The IOP was elevated to 35.4 (3.3) mmHg and 34.4 (2.5) mmHg in the emmetropic and myopic groups, respectively. When compared with their baseline values, the cupping variables (CA and CV) were significantly increased (p <0.05) during the suction treatment in both emmetropic and myopic subjects. Conclusion. There was a significant enlargement in the optic disc cupping during the artificial increment of intraocular pressure in both emmetropic and myopic eyes. In non-glaucomatous eyes the optic nerve head has a partially dynamic topography dependent upon the level of IOP.