The air quality impact of cordon and distance based road user charging: an empirical study of Leeds, U.K

Traffic assignment, pollutant emission and dispersion models were applied to a major UK city so as to assess the air quality impacts of five road pricing schemes. Schemes were evaluated with reference to: exceedence of air quality standards for six pollutants; greenhouse gas emission; redistribution of pollution, an environmental justice concern; and road network performance as traffic speed and trip distance. Results were compared to alternatives of do nothing, network development and clean fuel promotion. The air quality benefits of a modest distance based charge are highlighted. However, whilst road pricing shows potential as an air quality management tool, its value and suitability are strongly sensitive to prior air quality and emission source apportionment in the application city

MAPK phosphorylation of connexin 43 promotes binding of cyclin E and smooth muscle cell proliferation

<p>Rationale: Dedifferentiation of vascular smooth muscle cells (VSMC) leading to a proliferative cell phenotype significantly contributes to the development of atherosclerosis. Mitogen-activated protein kinase (MAPK) phosphorylation of proteins including connexin 43 (Cx43) has been associated with VSMC proliferation in atherosclerosis.</p> <p>Objective: To investigate whether MAPK phosphorylation of Cx43 is directly involved in VSMC proliferation.</p> <p>Methods and Results: We show in vivo that MAPK-phosphorylated Cx43 forms complexes with the cell cycle control proteins cyclin E and cyclin-dependent kinase 2 (CDK2) in carotids of apolipoprotein-E receptor null (ApoE−/−) mice and in C57Bl/6 mice treated with platelet-derived growth factor–BB (PDGF). We tested the involvement of Cx43 MAPK phosphorylation in vitro using constructs for full-length Cx43 (Cx43) or the Cx43 C-terminus (Cx43CT) and produced null phosphorylation Ser>Ala (Cx43MK4A/Cx43CTMK4A) and phospho-mimetic Ser>Asp (Cx43MK4D/Cx43CTMK4D) mutations. Coimmunoprecipitation studies in primary VSMC isolated from Cx43 wild-type (Cx43+/+) and Cx43 null (Cx43−/−) mice and analytic size exclusion studies of purified proteins identify that interactions between cyclin E and Cx43 requires Cx43 MAPK phosphorylation. We further demonstrate that Cx43 MAPK phosphorylation is required for PDGF-mediated VSMC proliferation. Finally, using a novel knock-in mouse containing Cx43-MK4A mutation, we show in vivo that interactions between Cx43 and cyclin E are lost and VSMC proliferation does not occur after treatment of carotids with PDGF and that neointima formation is significantly reduced in carotids after injury.</p> <p>Conclusions: We identify MAPK-phosphorylated Cx43 as a novel interacting partner of cyclin E in VSMC and show that this interaction is critical for VSMC proliferation. This novel interaction may be important in the development of atherosclerotic lesions.</p&gt

Continuing professional development:introducing the ERS International Certificate in Respiratory Sleep Medicine

Certification of specialists in respiratory sleep medicine for the purposes of continuing professional developmen

The Ginzburg regime and its effects on topological defect formation

The Ginzburg temperature has historically been proposed as the energy scale of formation of topological defects at a second order symmetry breaking phase transition. More recently alternative proposals which compute the time of formation of defects from the critical dynamics of the system, have been gaining both theoretical and experimental support. We investigate, using a canonical model for string formation, how these two pictures compare. In particular we show that prolonged exposure of a critical field configuration to the Ginzburg regime results in no substantial suppression of the final density of defects formed. These results dismiss the recently proposed role of the Ginzburg regime in explaining the absence of topological defects in 4He pressure quench experiments.Comment: 8 pages, 5 ps figure

Phagosomal acidification Is required to kill Streptococcus pneumoniae in a Zebrafish model

Streptococcus pneumoniae (the pneumococcus) is a major human pathogen causing invasive disease, including community-acquired bacteraemia, and remains a leading cause of global mortality. Understanding the role of phagocytes in killing bacteria is still limited, especially in vivo. In this study, we established a zebrafish model to study the interaction between intravenously administered pneumococci and professional phagocytes such as macrophages and neutrophils, to unravel bacterial killing mechanisms employed by these immune cells. Our model confirmed the key role of polysaccharide capsule in promoting pneumococcal virulence through inhibition of phagocytosis. Conversely, we show pneumococci lacking a capsule are rapidly internalised by macrophages. Low doses of encapsulated S. pneumoniae cause near 100% mortality within 48 hours postinfection (hpi), while 50 times higher doses of unencapsulated pneumococci are easily cleared. Time course analysis of in vivo bacterial numbers reveals that while encapsulated pneumococcus proliferates to levels exceeding 105 CFU at the time of host death, unencapsulated bacteria are unable to grow and are cleared within 20 hpi. Using genetically induced macrophage depletion, we confirmed an essential role for macrophages in bacterial clearance. Additionally, we show that upon phagocytosis by macrophages, phagosomes undergo rapid acidification. Genetic and chemical inhibition of vacuolar ATPase (v-ATPase) prevents intracellular bacterial killing and induces host death indicating a key role of phagosomal acidification in immunity to invading pneumococci. We also show that our model can be used to study the efficacy of antimicrobials against pneumococci in vivo. Collectively, our data confirm that larval zebrafish can be used to dissect killing mechanisms during pneumococcal infection in vivo and highlight key roles for phagosomal acidification in macrophages for pathogen clearance

Impact of extractive industries on malaria prevalence in the Democratic Republic of the Congo: a population-based cross-sectional study

Extraction of natural resources through mining and logging activities provides revenue and employment across sub-Saharan Africa, a region with the highest burden of malaria globally. The extent to which mining and logging influence malaria transmission in Africa remains poorly understood. Here, we evaluate associations between mining, logging, and malaria in the high transmission setting of the Democratic Republic of the Congo using population-representative malaria survey results and geographic data for environmental features and mining and logging concessions. We find elevated malaria prevalence among individuals in rural areas exposed to mining; however, we also detect significant spatial confounding among locations. Upon correction, effect estimates for mining and logging shifted toward the null and we did not find sufficient evidence to detect an association with malaria. Our findings reveal a complex interplay between mining, logging, space, and malaria prevalence. While mining concessions alone may not drive the high prevalence, unobserved features of mining-exposed areas, such as human migration, changing vector populations, or parasite genetics, may instead be responsible

Ab initio and finite-temperature molecular dynamics studies of lattice resistance in tantalum

This manuscript explores the apparent discrepancy between experimental data and theoretical calculations of the lattice resistance of bcc tantalum. We present the first results for the temperature dependence of the Peierls stress in this system and the first ab initio calculation of the zero-temperature Peierls stress to employ periodic boundary conditions, which are those best suited to the study of metallic systems at the electron-structure level. Our ab initio value for the Peierls stress is over five times larger than current extrapolations of experimental lattice resistance to zero-temperature. Although we do find that the common techniques for such extrapolation indeed tend to underestimate the zero-temperature limit, the amount of the underestimation which we observe is only 10-20%, leaving open the possibility that mechanisms other than the simple Peierls stress are important in controlling the process of low temperature slip.Comment: 12 pages and 9 figure

The Intentional Use of Service Recovery Strategies to Influence Consumer Emotion, Cognition and Behaviour

Service recovery strategies have been identified as a critical factor in the success of. service organizations. This study develops a conceptual frame work to investigate how specific service recovery strategies influence the emotional, cognitive and negative behavioural responses of . consumers., as well as how emotion and cognition influence negative behavior. Understanding the impact of specific service recovery strategies will allow service providers' to more deliberately and intentionally engage in strategies that result in positive organizational outcomes. This study was conducted using a 2 x 2 between-subjects quasi-experimental design. The results suggest that service recovery has a significant impact on emotion, cognition and negative behavior. Similarly, satisfaction, negative emotion and positive emotion all influence negative behavior but distributive justice has no effect

Constructive Data Refinement in Typed Lambda Calculus

. A new treatment of data refinement in typed lambda calculus is proposed, phrased in terms of pre-logical relations [HS99] rather than logical relations, and incorporating a constructive element. Constructive data refinement is shown to have desirable properties, and a substantial example of refinement is presented. 1 Introduction One of the activities involved in developing programs from specifications is the transformation of "abstract programs" involving types of data that are not normally available as primitive in programming languages (graphs, sets, etc.) into "concrete programs" in which a representation of these in terms of simpler types of data is provided. Apart from the change to data representation, such data refinement should have no e#ect on the results computed by the program: the concrete program should be equivalent to the abstract program in the sense that all computational observations should return the same results in both cases. The standard treatment of data refi..