1,245 research outputs found

    Optimisation of policies for transport integration in metropolitan areas: report on work packages 30 and 40

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    The overall objectives of Project OPTIMA are:- (i) to identify optimal urban transport strategies for a range of urban areas within the EU; (ii) to compare the strategies which are specified as optimal in different cities, and to assess the reasons for these differences; (iii) to assess the acceptability and feasibility of implementation of these strategies both in the case study cities and more widely in the EU, and (iv) to use the results to provide more general guidance on urban transport policy within the EU. There is a wide range of objectives of transport policy in urban areas, but most can be grouped under the broad headings of economic efficiency, including economic development, on the one hand, and sustainability, including environment, safety, equity and quality of life, on the other. It is now generally accepted that the overall strategy for achieving these objectives must include an element of reduction of private car use and transfer of travel to other modes. The policy instruments for achieving these objectives can include infrastructure provision, management measures to enhance other modes and to restrict car use, and pricing measures to make public transport more attractive and to increase the marginal cost of car use. It is now widely accepted that the most appropriate strategy will involve several of these measures, combined in an integrated way which emphasises the synergy between them. The most appropriate strategy for a city will depend on its size, the current built form, topography, transport infrastructure and patterns of use; levels of car ownership, congestion and projected growth in travel; transport policy instruments already in use; and the acceptability of other measures in political and legislative terms. These will differ from city to city. Policy advice cannot therefore be generalised, but must be developed for a range of different types of city. This is the approach adopted in this study, in which nine different cities in five countries (Edinburgh, Merseyside, Vienna, Eisenstadt, Trams@, Oslo, Helsinki, Torino and Salerno) have been studied in detail, using a common study methodology. This report summarises the output of two work packages in OPTIMA: WP30: Test Combinations of Policy Instruments WP40: Identify Optim

    Effects of ErbB2 overexpression on the proteome and ErbB ligand-specific phosphosignalling in mammary luminal epithelial cells

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    Most breast cancers arise from luminal epithelial cells and 25-30% of these tumours overexpress the ErbB2/HER2 receptor which correlates with disease progression and poor prognosis. The mechanisms of ErbB2 signalling and the effects of its overexpression are not fully understood. Herein, SILAC expression profiling and phosphopeptide enrichment of a relevant, non-transformed, immortalized human mammary luminal epithelial cell model were used to profile ErbB2-dependent differences in protein expression and phosphorylation events triggered via EGFR (EGF treatment) and ErbB3 (HRG1β treatment) in the context of ErbB2 overexpression. Bioinformatics analysis was used to infer changes in cellular processes and signalling events. We demonstrate the complexity of the responses to oncogene expression and growth factor signalling and identify protein changes relevant to ErbB2-dependent altered cellular phenotype, in particular cell cycle progression and hyper-proliferation, reduced adhesion and enhanced motility. Moreover, we define a novel mechanism by which ErbB signalling suppresses basal interferon signalling that would promote the survival and proliferation of mammary luminal epithelial cells. Numerous novel sites of growth factor-regulated phosphorylation were identified that were enhanced by ErbB2 overexpression and we putatively link these to altered cell behaviour and also highlight the importance of performing parallel protein expression profiling alongside phosphoproteomic analysis

    Asymptotic Reduction of a Lithium-ion Pouch Cell Model

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    A three-dimensional model of a single-layer lithium-ion pouch cell is presented which couples conventional porous electrode theory describing cell electrochemical behaviour with an energy balance describing cell thermal behaviour. Asymptotic analysis of the model is carried out by exploiting the small aspect ratio typical of pouch cell designs. The analysis reveals the scaling that results in a distinguished limit, and highlights the role played by the electrical conductivities of the current collectors. The resulting model comprises a collection of one-dimensional models for the through-cell electrochemical behaviour which are coupled via two-dimensional problems for the Ohmic and thermal behaviour in the planar current collectors. A further limit is identified which reduces the problem to a single volume-averaged through-cell model, greatly reducing the computational complexity. Numerical simulations are presented which illustrate and validate the asymptotic results.Comment: 27 pages, 6 figures, submitted to SIAM Journal on Applied Mathematics (08/05/2020

    A Suite of Reduced-Order Models of a Single-Layer Lithium-ion Pouch Cell

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    For many practical applications, fully coupled three-dimensional models describing the behaviour of lithium-ion pouch cells are too computationally expensive. However, owing to the small aspect ratio of typical pouch cell designs, such models are well approximated by splitting the problem into a model for through-cell behaviour and a model for the transverse behaviour. In this paper, we combine different simplifications to through-cell and transverse models to develop a hierarchy of reduced-order pouch cell models. We give a critical numerical comparison of each of these models in both isothermal and thermal settings, and also study their performance on realistic drive cycle data. Finally, we make recommendations regarding model selection, taking into account the available computational resource and the quantities of interest in a particular study

    Evaluation of Teat Condition Using Liquid or Powder Dips in Winter

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    Objective of this study was to compares a 0.5% iodine aqueous teat dip vs 0.5% chlorhexidine gluconate powdered teat dip under winter conditions on overall teat end and teat skin condition and health. Under the conditions of this trial there were slight non-significant decreases in teat end condition associated with colder temperatures and temperature changes in both groups, with no differences between groups in TE change. Both groups saw some decreases in teat skin condition with powder dipped teats showing a 2 fold increased hazard of dry teat skin. Results of this trial show teat changes (skin and end condition) associated with cold temperature changes even under ideal (minimal wind) housing and different teat dips. Producers need to realize changes will occur, assess their own farm condition (housing, weather, wind) and be judicious in determining conditions requiring switches to winter dip products and practices

    Differential viral accessibility (DIVA) identifies alterations in chromatin architecture through large-scale mapping of lentiviral integration sites.

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    Alterations in chromatin structure play a major role in the epigenetic regulation of gene expression. Here, we describe a step-by-step protocol for differential viral accessibility (DIVA), a method for identifying changes in chromatin accessibility genome-wide. Commonly used methods for mapping accessible genomic loci have strong preferences toward detecting 'open' chromatin found at regulatory regions but are not well suited to studying chromatin accessibility in gene bodies and intergenic regions. DIVA overcomes this limitation, enabling a broader range of sites to be interrogated. Conceptually, DIVA is similar to ATAC-seq in that it relies on the integration of exogenous DNA into the genome to map accessible chromatin, except that chromatin architecture is probed through mapping integration sites of exogenous lentiviruses. An isogenic pair of cell lines are transduced with a lentiviral vector, followed by PCR amplification and Illumina sequencing of virus-genome junctions; the resulting sequences define a set of unique lentiviral integration sites, which are compared to determine whether genomic loci exhibit significantly altered accessibility between experimental and control cells. Experienced researchers will take 6 d to generate lentiviral stocks and transduce the target cells, a further 5 d to prepare the Illumina sequencing libraries and a few hours to perform the bioinformatic analysis

    Phylogenetic analysis of human Chlamydia pneumoniae strains reveals a distinct Australian indigenous clade that predates European exploration of the continent

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    © 2015 Roulis et al. Background: The obligate intracellular bacterium Chlamydia pneumoniae is a common respiratory pathogen, which has been found in a range of hosts including humans, marsupials and amphibians. Whole genome comparisons of human C. pneumoniae have previously highlighted a highly conserved nucleotide sequence, with minor but key polymorphisms and additional coding capacity when human and animal strains are compared. Results: In this study, we sequenced three Australian human C. pneumoniae strains, two of which were isolated from patients in remote indigenous communities, and compared them to all available C. pneumoniae genomes. Our study demonstrated a phylogenetically distinct human C. pneumoniae clade containing the two indigenous Australian strains, with estimates that the most recent common ancestor of these strains predates the arrival of European settlers to Australia. We describe several polymorphisms characteristic to these strains, some of which are similar in sequence to animal C. pneumoniae strains, as well as evidence to suggest that several recombination events have shaped these distinct strains. Conclusions: Our study reveals a greater sequence diversity amongst both human and animal C. pneumoniae strains, and suggests that a wider range of strains may be circulating in the human population than current sampling indicates

    Characterization of Murine Thymic Stromal-Cell Lines Immortalized by Temperature-Sensitive Simian Virus 40 Large T or Adenovirus 5 E1a

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    The heterogeneity of thymic stromal cells is probably related to their role in providing different microenvironments where T cells can develop. We have immortalized thymic stromal elements using recombinant retroviral constructs containing a temperature-sensitive simian virus 40 (SV40tsA58) large-T antigen gene or the adenovirus 5 E1a region linked to the gene coding for resistance to G418. Cell lines containing the thermolabile large T antigen encoded by SV40 proliferate at the permissive temperature of 33°C and arrest growth when transferred to the nonpermissive temperature of 39°C. At the nonpermissive temperature, ts-derived cell lines are shown to alter their phenotype but remain metabolically active, as indicated by the inducible expression of class I and class II MHC antigens. Here we describe the generation of a total of 84 thymic stromal-cell lines, many of which show distinct morphologic, phenotypic, and functional properties consistent with fibroblastoid, epithelial, or monocytoid origins. Several E1a and SV40tsA58-derived cell lines generated exhibit the epithelial characteristic of desmosome formation and, in addition, two of these lines (15.5 and 15.18) form multicellular complexes (rosettes) when incubated with unfractionated thymocytes from syngeneic mice. A single line (14.5) displays very strong nonspecific esterase activity, suggesting it may represent a macrophagelike cell type. We describe the generation of stromal cell lines with different properties, which is consistent with the heterogeneity found in the thymic microenvironment. In addition to documenting this diversity, these cell lines may be useful tools for studying T-cell development in vitro and give access to model systems in which stromal-thymocyte interactions can be examined
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