336 research outputs found

    Quantitative measure of evolution of bright cluster galaxies at moderate redshifts

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    Using archival data from the Hubble Space Telescope, we study the quantitative morphological evolution of spectroscopically confirmed bright galaxies in the core regions of nine clusters ranging in redshift from z=0.31z = 0.31 to z=0.84z = 0.84. We use morphological parameters derived from two dimensional bulge-disk decomposition to study the evolution. We find an increase in the mean bulge-to-total luminosity ratio B/TB/T as the Universe evolves. We also find a corresponding increase in the fraction of early type galaxies and in the mean S\'ersic index. We discuss these results and their implications to physical mechanisms for evolution of galaxy morphology.Comment: 5 pages, 3 figures, Accepted for publication in MNRAS: Letter

    Towards a balanced scorecard: A critical analysis of the Culture and Sport Evidence (CASE) programme

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    This article provides a critical analysis of the methods employed in the Culture and Sport Evidence (CASE) programme. Based on a comprehensive review of the arts management and cultural policy literature, it contests recent claims that the cultural sector should state its value in the economic language of policy appraisal and evaluation (O’Brien, 2010) and proposes alternative methods for evaluating the drivers, impact and value of engagement in the arts, including the balanced scorecard approach. The literature identifies a number of fundamental problems in quantifying the social and personal impact of the arts, and an underlying policy issue is that the arts have become increasingly subject to the benchmarks of incompatible disciplines and practices. This paper seeks to redress the balance by questioning the argument that economic cost benefit analysis is the best way to understand cultural value and influence public policy. As the CASE programme aimed to make the business case for optimum Government investment in sport and culture, it adopted the framework set out in HM Treasury’s Green Book and took a quantitative, evidence-based approach to measuring the drivers, impact and instrumental value of engagement, disregarding established qualitative studies and approaches, which have been shown to articulate cultural value through a more personal, intrinsic and holistic lens. This article makes the case for a more balanced approach to cultural evaluation and a more holistic articulation of cultural value, which would combine intrinsic and instrumental benefits and comprise both qualitative and quantitative methods. The key implication of this re-conception of value is that cultural policy should be evaluated not on return on investment but rather against a balanced range of objectives and articulated in a language that reflects artistic practice and speaks directly to existing and potential audiences

    4-Deoxy-4-fluoro-GalNAz (4FGalNAz) is a metabolic chemical reporter of O-GlcNAc modifications, highlighting the notable substrate flexibility of O-GlcNAc transferase

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    Bio-orthogonal chemistries have revolutionized many fields. For example, metabolic chemical reporters (MCRs) of glycosylation are analogues of monosaccharides that contain a bio-orthogonal functionality, such as azides or alkynes. MCRs are metabolically incorporated into glycoproteins by living systems, and bio-orthogonal reactions can be subsequently employed to install visualization and enrichment tags. Unfortunately, most MCRs are not selective for one class of glycosylation (e.g., N-linked vs O-linked), complicating the types of information that can be gleaned. We and others have successfully created MCRs that are selective for intracellular O-GlcNAc modification by altering the structure of the MCR and thus biasing it to certain metabolic pathways and/or O-GlcNAc transferase (OGT). Here, we attempt to do the same for the core GalNAc residue of mucin O-linked glycosylation. The most widely applied MCR for mucin O-linked glycosylation, GalNAz, can be enzymatically epimerized at the 4-hydroxyl to give GlcNAz. This results in a mixture of cell-surface and O-GlcNAc labeling. We reasoned that replacing the 4-hydroxyl of GalNAz with a fluorine would lock the stereochemistry of this position in place, causing the MCR to be more selective. After synthesis, we found that 4FGalNAz labels a variety of proteins in mammalian cells and does not perturb endogenous glycosylation pathways unlike 4FGalNAc. However, through subsequent proteomic and biochemical characterization, we found that 4FGalNAz does not widely label cell-surface glycoproteins but instead is primarily a substrate for OGT. Although these results are somewhat unexpected, they once again highlight the large substrate flexibility of OGT, with interesting and important implications for intracellular protein modification by a potential range of abiotic and native monosaccharides

    Who uses sustainable land management practices and what are the costs and benefits? Insights from Kenya

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    Suboptimal land management practices are degrading soils and undermining food production. Sustainable land management (SLM) practices can improve soil and enhance yields. This study identifies variations in SLM uptake, characterising farmers most likely to use SLM practices, identifying when it makes economic sense for farmers to implement particular SLM practices and how long it takes before benefits exceed costs. Using questionnaire data from farmers in western Kenya, we undertake a cost–benefit analysis and analyse determinants of SLM practice use. SLM implementation varied between counties and SLM practice(s), with household and farm characteristics, and access to assets and advice, playing a key role. SLM practices with high upfront and maintenance costs (e.g., terraces and agroforestry) offer low benefit‐to‐cost ratios for individual farmers who must also wait many years to break even on their investments. Nevertheless, over the policy‐relevant time horizon considered (to 2030), Net present value can be positive. Simple SLM practices (manuring and intercropping) have low input costs and offer high benefit to cost ratios, providing a positive net present value up to 2030. Findings suggest that simple practices should be prioritised within policy to improve soil and increase yields. These should be supported by subsidies or other economic measures, facilitating uptake of practices such as agroforestry, which can provide wider societal benefits (e.g., improved water retention and carbon sequestration). Economic mechanisms could be augmented with support for agricultural innovation systems, improved monitoring of land management and yield relationships, and investment in climate and soil information services

    IMCI and ETAT Integration at a Primary Healthcare Facility in Malawi:A Human Factors Approach

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    Abstract Background Integrated Management of Childhood Illness (IMCI) and Emergency Triage, Assessment and Treatment (ETAT) are guidelines developed by the World Health Organization to reach targets for reducing under-5 mortality. They were set out in the Millennium Development Goals. Each guideline was established separately so the purpose of this study was to understand how these systems have been integrated in a primary care setting and identify barriers and facilitators to this integration using a systems approach. Method Interviews were carried out with members of staff of different levels within a primary healthcare clinic in Malawi. Along with observations from the clinic this provided a well-rounded view of the running of the clinic. This data was then analysed using the SEIPS 2.0 work systems framework. The work system elements specified in this model were used to identify and categorise themes that influenced the clinic’s efficiency. Results A process map of the flow of patients through the clinic was created, showing the tasks undertaken and the interactions between staff and patients. In their interviews, staff identified several organisational elements that served as barriers to the implementation of care. They included workload, available resources, ineffective time management, delegation of roles and adaptation of care. In terms of the external environment there was a lack of clarity over the two sets of guidelines and how they were to be integrated which was a key barrier to the process. Under the heading of tools and technology a lack of guideline copies was identified as a barrier. However, the health passport system and other forms of recording were highlighted as being important facilitators. Other issues highlighted were the lack of transport provided, challenges regarding teamwork and attitudes of members of staff, patient factors such as their beliefs and regard for the care and education provided by the clinic. Conclusions This study provides the first information on the challenges and issues involved in combining IMCI and ETAT and identified a number of barriers. These barriers included a lack of resources, staff training and heavy workload. This provided areas to work on in order to improve implementation

    UDP-Galactose 4′-Epimerase Activities toward UDP-Gal and UDP-GalNAc Play Different Roles in the Development of Drosophila melanogaster

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    In both humans and Drosophila melanogaster, UDP-galactose 4′-epimerase (GALE) catalyzes two distinct reactions, interconverting UDP-galactose (UDP-gal) and UDP-glucose (UDP-glc) in the final step of the Leloir pathway of galactose metabolism, and also interconverting UDP-N-acetylgalactosamine (UDP-galNAc) and UDP-N-acetylglucosamine (UDP-glcNAc). All four of these UDP-sugars serve as vital substrates for glycosylation in metazoans. Partial loss of GALE in humans results in the spectrum disorder epimerase deficiency galactosemia; partial loss of GALE in Drosophila melanogaster also results in galactose-sensitivity, and complete loss in Drosophila is embryonic lethal. However, whether these outcomes in both humans and flies result from loss of one GALE activity, the other, or both has remained unknown. To address this question, we uncoupled the two activities in a Drosophila model, effectively replacing the endogenous dGALE with prokaryotic transgenes, one of which (Escherichia coli GALE) efficiently interconverts only UDP-gal/UDP-glc, and the other of which (Plesiomonas shigelloides wbgU) efficiently interconverts only UDP-galNAc/UDP-glcNAc. Our results demonstrate that both UDP-gal and UDP-galNAc activities of dGALE are required for Drosophila survival, although distinct roles for each activity can be seen in specific windows of developmental time or in response to a galactose challenge. By extension, these data also suggest that both activities might play distinct and essential roles in humans

    Inhibition of S6K1 accounts partially for the anti-inflammatory effects of the arginase inhibitor L-norvaline

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    <p>Abstract</p> <p>Background</p> <p>Pharmacological inhibition of endothelial arginase-II has been shown to improve endothelial nitric oxide synthase (eNOS) function and reduce atherogenesis in animal models. We investigated whether the endothelial arginase II is involved in inflammatory responses in endothelial cells.</p> <p>Methods</p> <p>Human endothelial cells were isolated from umbilical veins and stimulated with TNFα (10 ng/ml) for 4 hours. Endothelial expression of the inflammatory molecules i.e. vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin were assessed by immunoblotting.</p> <p>Results</p> <p>The induction of the expression of endothelial VCAM-1, ICAM-1 and E-selectin by TNFα was concentration-dependently reduced by incubation of the endothelial cells with the arginase inhibitor L-norvaline. However, inhibition of arginase by another arginase inhibitor S-(2-boronoethyl)-L-cysteine (BEC) had no effects. To confirm the role of arginase-II (the prominent isoform expressed in HUVECs) in the inflammatory responses, adenoviral mediated siRNA silencing of arginase-II knocked down the arginase II protein level, but did not inhibit the up-regulation of the adhesion molecules. Moreover, the inhibitory effect of L-norvaline was not reversed by the NOS inhibitor L-NAME and L-norvaline did not interfere with TNFα-induced activation of NF-κB, JNK, p38mapk, while it inhibited p70s6k (S6K1) activity. Silencing S6K1 prevented up-regulation of E-selectin, but not that of VCAM-1 or ICAM-1 induced by TNFα.</p> <p>Conclusion</p> <p>The arginase inhibitor L-norvaline exhibits anti-inflammatory effects independently of inhibition of arginase in human endothelial cells. The anti-inflammatory properties of L-norvaline are partially attributable to its ability to inhibit S6K1.</p

    Identification of alternative splice variants in Aspergillus flavus through comparison of multiple tandem MS search algorithms

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    <p>Abstract</p> <p>Background</p> <p>Database searching is the most frequently used approach for automated peptide assignment and protein inference of tandem mass spectra. The results, however, depend on the sequences in target databases and on search algorithms. Recently by using an alternative splicing database, we identified more proteins than with the annotated proteins in <it>Aspergillus flavus</it>. In this study, we aimed at finding a greater number of eligible splice variants based on newly available transcript sequences and the latest genome annotation. The improved database was then used to compare four search algorithms: Mascot, OMSSA, X! Tandem, and InsPecT.</p> <p>Results</p> <p>The updated alternative splicing database predicted 15833 putative protein variants, 61% more than the previous results. There was transcript evidence for 50% of the updated genes compared to the previous 35% coverage. Database searches were conducted using the same set of spectral data, search parameters, and protein database but with different algorithms. The false discovery rates of the peptide-spectrum matches were estimated < 2%. The numbers of the total identified proteins varied from 765 to 867 between algorithms. Whereas 42% (1651/3891) of peptide assignments were unanimous, the comparison showed that 51% (568/1114) of the RefSeq proteins and 15% (11/72) of the putative splice variants were inferred by all algorithms. 12 plausible isoforms were discovered by focusing on the consensus peptides which were detected by at least three different algorithms. The analysis found different conserved domains in two putative isoforms of UDP-galactose 4-epimerase.</p> <p>Conclusions</p> <p>We were able to detect dozens of new peptides using the improved alternative splicing database with the recently updated annotation of the <it>A. flavus </it>genome. Unlike the identifications of the peptides and the RefSeq proteins, large variations existed between the putative splice variants identified by different algorithms. 12 candidates of putative isoforms were reported based on the consensus peptide-spectrum matches. This suggests that applications of multiple search engines effectively reduced the possible false positive results and validated the protein identifications from tandem mass spectra using an alternative splicing database.</p

    Epidemiology and outcomes of people with dementia, delirium and unspecified cognitive impairment in the general hospital: prospective cohort study of 10,014 admissions

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    Background&nbsp; Cognitive impairment of various kinds is common in older people admitted to hospital, but previous research has usually focused on single conditions in highly-selected groups and has rarely examined associations with outcomes. This study examined prevalence and outcomes of cognitive impairment in a large unselected cohort of people aged 65+ with an emergency medical admission.&nbsp; Methods&nbsp; Between January 1, 2012, and June 30, 2013, admissions to a single general hospital acute medical unit aged 65+ underwent a structured specialist nurse assessment (n = 10,014). We defined &lsquo;cognitive spectrum disorder&rsquo; (CSD) as any combination of delirium, known dementia, or Abbreviated Mental Test (AMT) score &lt; 8/10. Routine data for length of stay (LOS), mortality, and readmission were linked to examine associations with outcomes.&nbsp; Results&nbsp; A CSD was present in 38.5% of all patients admitted aged over 65, and in more than half of those aged over 85. Overall, 16.7% of older people admitted had delirium alone, 7.9% delirium superimposed on known dementia, 9.4% known dementia alone, and 4.5% unspecified cognitive impairment (AMT score &lt; 8/10, no delirium, no known dementia). Of those with known dementia, 45.8% had delirium superimposed. Outcomes were worse in those with CSD compared to those without &ndash; LOS 25.0 vs. 11.8 days, 30-day mortality 13.6% vs. 9.0%, 1-year mortality 40.0% vs. 26.0%, 1-year death or readmission 62.4% vs. 51.5% (allP &lt; 0.01). There was relatively little difference by CSD type, although people with delirium superimposed on dementia had the longest LOS, and people with dementia the worst mortality at 1 year.&nbsp; Conclusions&nbsp; CSD is common in older inpatients and associated with considerably worse outcomes, with little variation between different types of CSD. Healthcare systems should systematically identify and develop care pathways for older people with CSD admitted as medical emergencies, and avoid only focusing on condition-specific pathways such as those for dementia or delirium alone
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