Methodology for assessing regional economic impacts of charging HGVs in Spain: an integrated approach through a random utility based multiregional input-output and a road transportation network model

An integrated approach composed of a random utility-based multiregional input-output model and a road transport network model was developed for evaluating the application of a fee to heavy-goods vehicles (HGVs) in Spain. For this purpose, a distance-based charge scenario (in euros per vehicle kilometer) for HGVs was evaluated for a selected motorway network in Spain. Although the aim of this charging policy was to increase the efficiency of transport, the approach strongly identified direct and indirect impacts on the regional economy. Estimates of the magnitude and extent of indirect effects on aggregated macroeconomic indicators (employment and gross domestic product) are provided. The macroeconomic effects of the charging policy were found to be positive for some regions and negative for other regions.

A random utility based multiregional input-output approach to estimate the impact of a new highway on the regional distribution of jobs

This paper addresses the economic impact assessment of the construction of a new road on the regional distribution of jobs. The paper summarizes different existing model approaches considered to assess economic impacts through a literature review. Afterwards, we present the development of a comprehensive approach for analyzing the interaction of new transport infrastructure and the economic impact through an integrated model. This model has been applied to the construction of the motorway A-40 in Spain (497 Km.) which runs across three regions without passing though Madrid City. This may in turn lead to the relocation of labor and capital due to the improvement of accessibility of markets or inputs. The result suggests the existence of direct and indirect effects in other regions derived from the improvement of the transportation infrastructure, and confirms the relevance of road freight transport in some regions. We found that the changes in regional employment are substantial for some regions (increasing or decreasing jobs), but a t the same time negligible in other regions. As a result,the approach provides broad guidance to national governments and other transport-related parties about the impacts of this transport policy.

An Integrated Transport Planning Framework Involving a Combined Utility-Regret Approach

Sustainable transport planning requires an integrated approach involving strategic planning, impact analysis and multi-criteria evaluation. This study aims at relaxing the utility-based decision-making assumption by newly embedding anticipated-regret and combined utility-regret decision mechanisms in an integrated transport planning framework. The framework consists of a two-round Delphi survey, an integrated land-use and transport model for Madrid, and multi-criteria analysis. Results show that (i) regret-based ranking has similar mean but larger variance than utility-based ranking; (ii) the least-regret scenario forms a compromise between the desired and the expected scenarios; (iii) the least-regret scenario can lead to higher user benefits in the short-term and lower user benefits in the long-term; (iv) utility-based, regret-based and combined utility-regret-based multi-criteria analysis result in different rankings of policy packages; and (v) the combined utility-regret ranking is more informative compared with utility-based or regret-based ranking.

One-dimensional linear analysis of the compound jet

The stability of an infinitely long compound liquid column is analysed by using a one-dimensional inviscid slice model. Results obtained from this one-dimensional linear analysis are applicable to the study of compound capillary jets, which are used in the ink-jet printing technique. Stability limits and the breaking regimes of such fluid configurations are established, and, whenever possible, theoretical results are compared with experimental ones.

Qualitative operational value at risk for an electric utility based on the guidelines of the basel committee

This paper presents a model for determining value at operational risk ?OpVaR? in electric utilities, with the aim to confirm the versatility of the Bank for International Settlements (BIS) proposals. The model intends to open a new methodological approach in risk management, paying special attention to underlying operational sources of risk.

Incorporating equity into transport planning: utility, priority and sufficiency approaches

The analysis addresses the issue of transport equity and explores three different approaches to equity in transport: utilitarianism, sufficientarianism and prioritarianism. Each approach calls for a different treatment of the benefits reaped by different population groups in the assessment of transport investments or policies. In utilitarianism, which underlies much of the current practice of transport project appraisal, all benefits receive the same weight, irrespective of the recipient of the benefits. In both sufficientarianism and prioritarianism, benefits are weighed in distinct ways, depending on the characteristics of the recipients. The three approaches are illustrated using a fictive case study, in which three different transport investment are assessed and compared to each other. Finally, the assessment of transport investments will be explored using the cost-effectiveness analysis (CEA). The CEA assesses the distributional effects of transport investments for utilitarism, sufficientarism and prioritarism approaches and addresses distinct needs associated with different population groups in respect to their transport

Simultaneous determination of helical unwinding angles and intrinsic association constants in ligand–DNA complexes: The interaction between DNA and calichearubicin B

We present a helical unwinding assay for reversibly binding DNA ligands that uses closed circular DNA, topoisomerase I (Topo I), and two-dimensional agarose gel electrophoresis. Serially diluted Topo I relaxation reactions at constant DNA/ligand ratio are performed, and the resulting apparent unwinding of the closed circular DNA is used to calculate both ligand unwinding angle (φ) and intrinsic association constant (Ka). Mathematical treatment of apparent unwinding is formally analogous to that of apparent extinction coefficient data for optical binding titrations. Extrapolation to infinite DNA concentration yields the true unwinding angle of a given ligand and its association constant under Topo I relaxation conditions. Thus this assay delivers simultaneous structural and thermodynamic information describing the ligand–DNA complex. The utility of this assay has been demonstrated by using calichearubicin B (CRB), a synthetic hybrid molecule containing the anthraquinone chromophore of (DA) and the carbohydrate domain of calicheamicin γ1I. The unwinding angle for CRB calculated by this method is −5.3 ± 0.5°. Its Ka value is 0.20 × 106 M−1. For comparison, the unwinding angles of ethidium bromide and DA have been independently calculated, and the results are in agreement with canonical values for these compounds. Although a stronger binder to selected sites, CRB is a less potent unwinder than its parent compound DA. The assay requires only small amounts of ligand and offers an attractive option for analysis of DNA binding by synthetic and natural compounds.

Feasibility and utility of population-level geospatial injury profiling : prospective, national cohort study

The Health Services Research Unit receives funding from the Chief Scientist Office of the Scottish Government Health and Social Care Directorates. The opinions expressed in this article are those of the authors alone. The GEOS study was funded by the North of Scotland Planning Group.

Search for the pathogenesis of the differing phenotype in two compound heterozygote Hungarian brothers with the same genotypic triosephosphate isomerase deficiency

In a Hungarian family with triosephosphate isomerase (TPI) deficiency, two compound heterozygote brothers were found with the same severe decrease in TPI activity, but only one of them had the classical symptoms. In search for the pathogenesis of the differing phenotype of the same genotypic TPI deficiency, an increase in red cell membrane fluidity was found. There were roughly 100% and 30% more 16:0/20:4 and 18:0/20:4 diacyl-phosphatidylcholine species in erythrocytes from the two TPI-deficient brothers than in the probes from healthy controls. The activities of acethylcholinesterase and calmodulin induced Ca2+ ATPase were significantly enhanced in erythrocytes from the propositus as compared with those of the neurologically symptom-free brother and other members of the TPI-deficient family as well as to those from healthy controls. Both enzymes are crucially involved in the function of nerve cells. The observed differences in membrane fluidity and enzyme activities between the erythrocytes from the phenotypically differing TPI-deficient brothers underline the importance of investigations into the effect of biophysical changes in the lipid environment of the membrane proteins on the development of disseminated focal neurological disorders of unknown pathogenic origin.

Reduced facilitation and vesicular uptake in crustacean and mammalian neuromuscular junction by T-588, a neuroprotective compound

Bath application of compound T-588, a neuroprotective agent, reduced paired-pulse and repetitive-pulse facilitation at mammalian and crustacean neuromuscular junctions. In addition, it reduced voltage-gated sodium and potassium currents in a use-dependent fashion, but had only a small effect on the presynaptic Ca2+ conductance. By contrast, it blocked FM 1–43 vesicular uptake but not its release, in both species. Postsynaptically, T-588 reduced acetylcholine currents at the mammalian junction in a voltage-independent manner, but had no effect on the crayfish glutamate junction. All of these effects were rapidly reversible and were observed at concentrations close to the compound’s acute protective level. We propose that this set of mechanisms, which reduces high-frequency synaptic transmission, is an important contributory factor in the neuroprotective action of T-588.

ER-27319, an acridone-related compound, inhibits release of antigen-induced allergic mediators from mast cells by selective inhibition of Fcɛ receptor I-mediated activation of Syk

Engagement of the mast cell high-affinity receptor for immunoglobulin E (IgE), FcɛRI, induces tyrosine phosphorylation of Syk, a non-receptor tyrosine kinase, that has been demonstrated as critical for degranulation. Herein we describe a synthetic compound, ER-27319, as a potent and selective inhibitor of antigen or anti-IgE-mediated degranulation of rodent and human mast cells. ER-27319 affected neither Lyn kinase activity nor the antigen-induced phosphorylation of the FcɛRI but did effectively inhibit the tyrosine phosphorylation of Syk and thus its activity. As a consequence, tyrosine phosphorylation of phospholipase C-γ1, generation of inositol phosphates, release of arachidonic acid, and secretion of histamine and tumor necrosis factor α were also inhibited. ER-27319 did not inhibit the anti-CD3-induced tyrosine phosphorylation of phospholipase C-γ1 in Jurkat T cells, demonstrating a specificity for Syk-induced signals. In contrast the tyrosine phosphorylation and activation of Syk, induced by in vitro incubation with the phosphorylated immunoreceptor tyrosine-based activation motif (ITAM) of FcɛRI γ subunit or by antigen activation of RBL-2H3 cells, was specifically inhibited by ER-27319. However, when ER-27319 was added to immunoprecipitated Syk, derived from activated cells, no effect was seen on Syk activity. ER-27319 did not inhibit the tyrosine phosphorylation of Syk induced by activation in the presence of Igβ ITAM or the anti-IgM-induced phosphorylation of Syk in human peripheral B cells. Therefore, ER-27319 selectively interferes with the FcɛRI γ phospho-ITAM activation of Syk in vitro and in intact cells. These results confirm the importance of Syk in FcɛRI-mediated responses in mast cells and demonstrate the mast cell selectivity and therapeutic potential of ER-27319 in the treatment of allergic disease.

Inhibition of Secretion by 1,3-Cyclohexanebis(methylamine), a Dibasic Compound That Interferes with Coatomer Function

We noted previously that certain aminoglycoside antibiotics inhibit the binding of coatomer to Golgi membranes in vitro. The inhibition is mediated in part by two primary amino groups present at the 1 and 3 positions of the 2-deoxystreptamine moiety of the antibiotics. These two amines appear to mimic the ε-amino groups present in the two lysine residues of the KKXX motif that is known to bind coatomer. Here we report the effects of 1,3-cyclohexanebis(methylamine) (CBM) on secretion in vivo, a compound chosen for study because it contains primary amino groups that resemble those in 2-deoxystreptamine and it should penetrate lipid bilayers more readily than antibiotics. CBM inhibited coatomer binding to Golgi membranes in vitro and in vivo and inhibited secretion by intact cells. Despite depressed binding of coatomer in vivo, the Golgi complex retained its characteristic perinuclear location in the presence of CBM and did not fuse with the endoplasmic reticulum (ER). Transport from the ER to the Golgi was also not blocked by CBM. These data suggest that a full complement of coat protein I (COPI) on membranes is not critical for maintenance of Golgi integrity or for traffic from the ER to the Golgi but is necessary for transport through the Golgi to the plasma membrane.

Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor

The phytochemical resveratrol, which is found in grapes and wine, has been reported to have a variety of anti-inflammatory, anti-platelet, and anti-carcinogenic effects. Based on its structural similarity to diethylstilbestrol, a synthetic estrogen, we examined whether resveratrol might be a phytoestrogen. At concentrations (≈3–10 μM) comparable to those required for its other biological effects, resveratrol inhibited the binding of labeled estradiol to the estrogen receptor and it activated transcription of estrogen-responsive reporter genes transfected into human breast cancer cells. This transcriptional activation was estrogen receptor-dependent, required an estrogen response element in the reporter gene, and was inhibited by specific estrogen antagonists. In some cell types (e.g., MCF-7 cells), resveratrol functioned as a superagonist (i.e., produced a greater maximal transcriptional response than estradiol) whereas in others it produced activation equal to or less than that of estradiol. Resveratrol also increased the expression of native estrogen-regulated genes, and it stimulated the proliferation of estrogen-dependent T47D breast cancer cells. We conclude that resveratrol is a phytoestrogen and that it exhibits variable degrees of estrogen receptor agonism in different test systems. The estrogenic actions of resveratrol broaden the spectrum of its biological actions and may be relevant to the reported cardiovascular benefits of drinking wine.