Understanding European Union international message telephone services demand

This study provides a contemporary understanding of demand relations in European Union (EU) international message telephone service (IMTS) markets prior to full liberalization at January 1 1998. Point-to-point demand equations that relate IMTS demand to prices, income, population and distance are estimated on bilateral market data for ten EU countries from 1990 to 1995. Model estimates suggest price elasticities of outgoing and incoming demand between 20.175 and 20.456, and 20.215 and 20.674, respectively. These elasticity estimates provide an empirical base from which to calculate welfare gains from the full deregulation of EU IMTS markets after 1998.Elasticity; European Union; International telephone demand

Ecological indicators for abandoned mines, Phase 1: Review of the literature

Mine waters have been identified as a significant issue in the majority of Environment Agency draft River Basin Management Plans. They are one of the largest drivers for chemical pollution in the draft Impact Assessment for the Water Framework Directive (WFD), with significant failures of environmental quality standards (EQS) for metals (particularly Cd, Pb, Zn, Cu, Fe) in many rivers linked to abandoned mines. Existing EQS may be overprotective of aquatic life which may have adapted over centuries of exposure. This study forms part of a larger project to investigate the ecological impact of metals in rivers, to develop water quality targets (alternative objectives for the WFD) for aquatic ecosystems impacted by long-term mining pollution. The report reviews literature on EQS failures, metal effects on aquatic biota and effects of water chemistry, and uses this information to consider further work. A preliminary assessment of water quality and biology data for 87 sites across Gwynedd and Ceredigion (Wales) shows that existing Environment Agency water quality and biology data could be used to establish statistical relations between chemical variables and metrics of ecological quality. Visual representation and preliminary statistical analyses show that invertebrate diversity declines with increasing zinc concentration. However, the situation is more complex because the effects of other metals are not readily apparent. Furthermore, pH and aluminium also affect streamwater invertebrates, making it difficult to tease out toxicity due to individual mine-derived metals. The most characteristic feature of the plant communities of metal-impacted systems is a reduction in diversity, compared to that found in comparable unimpacted streams. Some species thrive in the presence of heavy metals, presumably because they are able to develop metal tolerance, whilst others consistently disappear. Effects are, however, confounded by water chemistry, particularly pH. Tolerant species are spread across a number of divisions of photosynthetic organisms, though green algae, diatoms and blue-green algae are usually most abundant, often thriving in the absence of competition and/or grazing. Current UK monitoring techniques focus on community composition and, whilst these provide a sampling and analytical framework for studies of metal impacts, the metrics are not sensitive to these impacts. There is scope for developing new metrics, based on community-level analyses and for looking at morphological variations common in some taxa at elevated metal concentrations. On the whole, community-based metrics are recommended, as these are easier to relate to ecological status definitions. With respect to invertebrates and fish, metals affect individuals, population and communities but sensitivity varies among species, life stages, sexes, trophic groups and with body condition. Acclimation or adaptation may cause varying sensitivity even within species. Ecosystem-scale effects, for example on ecological function, are poorly understood. Effects vary between metals such as cadmium, copper, lead, chromium, zinc and nickel in order of decreasing toxicity. Aluminium is important in acidified headwaters. Biological effects depend on speciation, toxicity, availability, mixtures, complexation and exposure conditions, for example discharge (flow). Current water quality monitoring is unlikely to detect short-term episodic increases in metal concentrations or evaluate the bioavailability of elevated metal concentrations in sediments. These factors create uncertainty in detecting ecological impairment in metal-impacted ecosystems. Moreover, most widely used biological indicators for UK freshwaters were developed for other pressures and none distinguishes metal impacts from other causes of impairment. Key ecological needs for better regulation and management of metals in rivers include: i) models relating metal data to ecological data that better represent influences on metal toxicity; ii) biodiagnostic indices to reflect metal effects; iii) better methods to identify metal acclimation or adaptation among sensitive taxa; iv) better investigative procedures to isolate metal effects from other pressures. Laboratory data on the effects of water chemistry on cationic metal toxicity and bioaccumulation show that a number of chemical parameters, particularly pH, dissolved organic carbon (DOC) and major cations (Na, Mg, K, Ca) exert a major influence on the toxicity and/or bioaccumulation of cationic metals. The biotic ligand model (BLM) provides a conceptual framework for understanding these water chemistry effects as a combination of the influence of chemical speciation, and metal uptake by organisms in competition with H+ and other cations. In some cases where the BLM cannot describe effects, empirical bioavailable models have been successfully used. Laboratory data on the effects of metal mixtures across different water chemistries are sparse, with implications for transferring understanding to mining-impacted sites in the field where mixture effects are likely. The available field data, although relatively sparse, indicate that water chemistry influences metal effects on aquatic ecosystems. This occurs through complexation reactions, notably involving dissolved organic matter and metals such as Al, Cu and Pb. Secondly, because bioaccumulation and toxicity are partly governed by complexation reactions, competition effects among metals, and between metals and H+, give rise to dependences upon water chemistry. There is evidence that combinations of metals are active in the field; the main study conducted so far demonstrated the combined effects of Al and Zn, and suggested, less certainly, that Cu and H+ can also contribute. Chemical speciation is essential to interpret and predict observed effects in the field. Speciation results need to be combined with a model that relates free ion concentrations to toxic effect. Understanding the toxic effects of heavy metals derived from abandoned mines requires the simultaneous consideration of the acidity-related components Al and H+. There are a number of reasons why organisms in waters affected by abandoned mines may experience different levels of metal toxicity than in the laboratory. This could lead to discrepancies between actual field behaviour and that predicted by EQS derived from laboratory experiments, as would be applied within the WFD. The main factors to consider are adaptation/acclimation, water chemistry, and the effects of combinations of metals. Secondary effects are metals in food, metals supplied by sediments, and variability in stream flows. Two of the most prominent factors, namely adaptation/ acclimation and bioavailability, could justify changes in EQS or the adoption of an alternative measure of toxic effects in the field. Given that abandoned mines are widespread in England and Wales, and the high cost of their remediation to meet proposed WFD EQS criteria, further research into the question is clearly justified. Although ecological communities of mine-affected streamwaters might be over-protected by proposed WFD EQS, there are some conditions under which metals emanating from abandoned mines definitely exert toxic effects on biota. The main issue is therefore the reliable identification of chemical conditions that are unacceptable and comparison of those conditions with those predicted by WFD EQS. If significant differences can convincingly be demonstrated, the argument could be made for alternative standards for waters affected by abandoned mines. Therefore in our view, the immediate research priority is to improve the quantification of metal effects under field circumstances. Demonstration of dose-response relationships, based on metal mixtures and their chemical speciation, and the use of better biological tools to detect and diagnose community-level impairment, would provide the necessary scientific information

Th1 responsiveness to nephritogenic antigens determines susceptibility to crescentic glomerulonephritis in mice

Th1 responsiveness to nephritogenic antigens determines susceptibility to crescentic glomerulonephritis in mice. The pattern of glomerulonephritis (GN) developing in response to a planted antigen (sheep anti-mouse GBM globulin) was compared in two strains of mice which demonstrated either a predominant Th1 (C57BL/6) or Th2 (BALB/c) response to this antigen. GN was induced with a subnephritogenic i.v. dose of sheep anti-mouse GBM globulin in mice presensitized to sheep globulin. Sensitized C57BL/6 mice showed pronounced cutaneous delayed-type hypersensitivity (DTH) following the challenge with sheep globulin, low titers of circulating anti-sheep globulin antibody and high interferon γ (IFNγ) and low interleukin 4 (IL-4) production by splenic T cells, consistent with a predominant Th1 pattern of immune response. Sensitized BALB/c mice did not develop DTH following cutaneous challenge with sheep globulin, had higher circulating anti-sheep globulin antibody titers, and showed high IL-4 and low IFNγ production by splenic T cells compared with C57BL/6 mice, consistent with a predominant Th2 response. In C57BL/6 mice, GN developing in response to sheep globulin exhibited a severe crescentic pattern with prominent glomerular T cell and macrophage influx and fibrin deposition. In vivo depletion with a monoclonal anti-CD4 antibody demonstrated that this injury was T helper cell dependent. Treatment with monoclonal anti-mouse IFNγ antibody significantly reduced glomerular injury and crescent formation and attenuated the cutaneous DTH response. GN induced by the same protocol in BALB/c mice exhibited pronounced glomerular IgG and complement deposition. Crescent formation, fibrin deposition, and glomerular T cell and macrophage infiltration were significantly less than observed in C57BL/6 mice, and injury was not T cell dependent in the effector phase. These data suggest that the pattern of glomerular injury induced by a planted antigen can be determined by the balance of T helper cell subset activation. A Th1 response induces a severe crescentic pattern of GN, which like cutaneous DTH, is T helper cell and IFNγ dependent

The development and sea trials of a subsea holographic camera for large volume in-situ recording of marine organisms

We describe the development, construction and sea testing of an underwater holographic camera (HoloCam) for in situ recording of marine organisms and particles in large volumes of sea water. HoloCam comprises a laser, power supply, holographic recording optics and plate holders, a water-tight housing and a support frame. Added to this are control electronics such that the entire camera is remotely operable and controllable from ship or dock-side. Uniquely the camera can simultaneously record both in-line and off-axis holograms using a pulsed frequency doubled Nd-YAG laser. In-line holography is capable of producing images of organisms with a resolution of better than 10 Pm (at concentrations up to a few thousand per cubic centimetre at the smallest sizes). Off-axis holograms of aquatic systems of up to 50,000 cm3 volume, have been recorded. Following initial laboratory testing, the holo-camera was evaluated in an observation tank and ultimately was tested in Loch Etive, Scotland. In-line and off-axis holograms were recorded to a depth of 100 m. We will present results on the test dives and evaluation of the camera performance

Fibrin independent proinflammatory effects of tissuefactor in experimental crescentic glomerulonephritis

Fibrin independent proinflammatory effects of tissue factor in experimental crescentic glomerulonephritis.BackgroundTissue factor initiated glomerular fibrin deposition is an important mediator of injury in crescentic glomerulonephritis. Recent data have suggested noncoagulant roles for tissue factor in inflammation.MethodsTo test the hypothesis that in addition to its effects in initiating coagulation, tissue factor has proinflammatory effects in glomerulonephritis, rabbits given crescentic anti-glomerular basement membrane (GBM) antibody–induced glomerulonephritis were defibrinogenated with ancrod. One group of defibrinogenated rabbits was also given anti-tissue factor antibodies. Comparisons were made between these groups, as well as a third group that was neither defibrinogenated with ancrod nor given anti-tissue factor antibodies.ResultsDefibrinogenation alone abolished glomerular fibrin deposition, reduced crescent formation, and limited renal impairment (ancrod-treated, serum creatinine 274 ± 37 μmol/L; untreated 415 ± 51 μmol/L; P < 0.01). Tissue factor inhibition in defibrinogenated rabbits resulted in further protection of renal function (creatinine 140 ± 19 μmol/L, P < 0.01) and reduced proteinuria (0.4 ± 0.2g/day, untreated 2.6 ± 0.4 g/day, P <0.01), which was significantly increased by defibrinogenation alone (ancrod-treated, 5.6 ± 1.2 g/day). Anti-tissue factor antibodies (but not defibrinogenation alone) attenuated glomerular T-cell and macrophage recruitment, and major histocompatibility complex (MHC) class II expression.ConclusionThese results demonstrate important proinflammatory effects of tissue factor in crescentic glomerulonephritis that are fibrin independent and provide in vivo evidence for tissue factor's proinflammatory effects on MHC class II expression and leukocyte accumulation

HoloCam: A subsea holographic camera for recording marine organisms and particles

The HoloCam system is a major component of a multi-national multi-discipline project known as HoloMar (funded by the European Commission under the MAST III initiative). The project is concerned with the development of pulsed laser holography to analyse and monitor the populations of living organisms and inanimate particles within the world's oceans. We describe here the development, construction and evaluation of a prototype underwater camera, the purpose of which is to record marine organisms and particles, in-situ. Recording using holography provides several advantages over conventional sampling methods in that it allows non-intrusive, non-destructive, high-resolution imaging of large volumes (up to 10^5 cm^3) in three dimensions. The camera incorporates both in-line and off-axis holographic techniques, which allows particles from a few micrometres to tens of centimetres to be captured. In tandem with development of the HoloCam, a dedicated holographic replay system and an automated data extraction and image processing facility are being developed. These will allow, optimisation of the images recorded by the camera, identification of species and particle concentration plotting

Proton binding by groundwater fulvic acids of different age, origins, and structure modeled with the model V and NICA-Donnan model

The proton binding properties of four fulvic acids from pristine groundwater and leachate-polluted groundwater were measured at four different ionic strengths (0.005−0.12 M) and modeled by the Model V and the NICA−Donnan model in order to evaluate the necessity of detailed proton binding parameters for groundwater fulvic acids. The proton binding parameters derived from the various fulvic acids were very similar, and on the basis of these parameters, it was not possible to distinguish between pristine and polluted groundwater. Normalization of the proton charge density by the proton charge density at pH 7 for each fulvic acid made all four fulvic acids regress to the same curve. The effects of varying the proton binding parameters were evaluated by simulating cadmium complexation using sets of proton binding parameters for the four fulvic acids and default sets of proton binding parameters available in the models WHAM (based on Model V) and Ecosat (based on NICA−Donnan). The Model V was rather indifferent with respect to specific characteristics of fulvic acids proton binding, and for most practical uses, the default values available in the model can be used. The NICA−Donnan model resulted in larger deviations between simulations based on default values and specific parameters. However, the NICA−Donnan database is still rather limited, and specific proton binding parameters should be used until the database providing default values has been extended

Imaging Drug Uptake by Bioorthogonal Stimulated Raman Scattering Microscopy

Stimulated Raman scattering (SRS) microscopy in tandem with bioorthogonal Raman labelling strategies is set to revolutionise the direct visualisation of intracellular drug uptake. Rational evaluation of a series of Raman-active labels has allowed the identification of highly active labels which have minimal perturbation on the biological efficacy of the parent drug. Drug uptake has been correlated with markers of cellular composition and cell cycle status, and mapped across intracellular structures using dual-colour and multi-modal imaging. The minimal phototoxicity and low photobleaching associated with SRS microscopy has enabled real-time imaging in live cells. These studies demonstrate the potential for SRS microscopy in the drug development process

Kinetic analysis of bioorthogonal reaction mechanisms using Raman microscopy

Raman spectroscopy is well-suited to the study of bioorthogonal reaction processes because it is a non-destructive technique, which employs relatively low energy laser irradiation, and water is only very weakly scattered in the Raman spectrum enabling live cell imaging. In addition, Raman spectroscopy allows species-specific label-free visualisation; chemical contrast may be achieved when imaging a cell in its native environment without fixatives or stains. Combined with the rapid advances in the field of Raman imaging over the last decade, particularly in stimulated Raman spectroscopy (SRS), this technique has the potential to revolutionise our mechanistic understanding of the biochemical and medicinal chemistry applications of bioorthogonal reactions. Current approaches to the kinetic analysis of bioorthogonal reactions (including heat flow calorimetry, UV-vis spectroscopy, fluorescence, IR, NMR and MS) have a number of practical shortcomings for intracellular applications. We highlight the advantages offered by Raman microscopy for reaction analysis in the context of both established and emerging bioorthogonal reactions, including the copper(i) catalysed azide-alkyne cycloaddition (CuAAC) click reaction and Glaser-Hay coupling