1,706 research outputs found
The case for joined-up research on carbon emissions from the building stock: adding value to household and building energy datasets
To reach UK objectives for reducing carbon emissions, it is argued that joined-up research on energy use in buildings is essential to develop and support government policy initiatives. The performance based approach introduced in Part-L of the 2006 Building Regulations has further underlined the role of coordinated research to monitor their effectiveness and provide feedback for subsequent revisions. Unfortunately, differences in dwelling classifications systems used in major household surveys currently hinder much of the supporting analysis that might improve SAP and other energy models. The Carbon Reduction in Buildings project has begun a process of integrating or organising existing building energy datasets into a coherent structure for the domestic sector. In addition, it is proposed to archive these for researchers via a building data repository that would facilitate joined-up research more widely
Mathematical modelling of oxygen, glucose and lactic acid reaction kinetics for osteoblasts and mesenchymal stem cells
Novel 2-amino-isoflavones exhibit aryl hydrocarbon receptor agonist or antagonist activity in a species/cell-specific context
The aryl hydrocarbon receptor (AhR) mediates the induction of a variety of xenobiotic metabolism genes. Activation of the AhR occurs through binding to a group of structurally diverse compounds, most notably dioxins, which are exogenous ligands. Isoflavones are part of a family which include some well characterised endogenous AhR ligands. This paper analysed a novel family of these compounds, based on the structure of 2-amino-isoflavone. Initially two luciferase-based cell models, mouse H1L6.1c2 and human HG2L6.1c3, were used to identify whether the compounds had AhR agonistic and/or antagonistic properties. This analysis showed that some of the compounds were weak agonists in mouse and antagonists in human. Further analysis of two of the compounds, Chr-13 and Chr-19, was conducted using quantitative real-time PCR in rat H4IIE and human MCF-7 cells. The results indicated that Chr-13 was an agonist in rat but an antagonist in human cells. Chr-19 was shown to be an agonist in rat but more interestingly, a partial agonist in human. Luciferase induction results not only revealed that subtle differences in the structure of the compound could produce species-specific differences in response but also dictated the ability of the compound to be an AhR agonist or antagonist. Substituted 2-amino-isoflavones represent a novel group of AhR ligands that must differentially interact with the AhR ligand binding domain to produce their species-specific agonist or antagonist activity and future ligand binding analysis and docking studies with these compounds may provide insights into the differential mechanisms of action of structurally similar compounds
The permeability of fractured rocks in pressurised volcanic and geothermal systems
AbstractThe connectivity of rocks’ porous structure and the presence of fractures influence the transfer of fluids in the Earth’s crust. Here, we employed laboratory experiments to measure the influence of macro-fractures and effective pressure on the permeability of volcanic rocks with a wide range of initial porosities (1–41 vol. %) comprised of both vesicles and micro-cracks. We used a hand-held permeameter and hydrostatic cell to measure the permeability of intact rock cores at effective pressures up to 30 MPa; we then induced a macro-fracture to each sample using Brazilian tensile tests and measured the permeability of these macro-fractured rocks again. We show that intact rock permeability increases non-linearly with increasing porosity and decreases with increasing effective pressure due to compactional closure of micro-fractures. Imparting a macro-fracture both increases the permeability of rocks and their sensitivity to effective pressure. The magnitude of permeability increase induced by the macro-fracture is more significant for dense rocks. We finally provide a general equation to estimate the permeability of intact and fractured rocks, forming a basis to constrain fluid flow in volcanic and geothermal systems.</jats:p
A Plug-and-Play Platform for the Formation of Trifunctional Cysteine Bioconjugates that also Offers Control over Thiol Cleavability
Linkers that enable the site-selective synthesis of chemically modified proteins are of great interest to the field of chemical biology. Homogenous bioconjugates often show advantageous pharmacokinetic profiles and consequently increased efficacy in vivo. Cysteine residues have been exploited as a route to site-selectively modify proteins, and many successfully approved therapeutics make use of cysteine directed conjugation reagents. However, commonly used linkers, including maleimide–thiol conjugates, are not stable to the low concentrations of thiol present in blood. Furthermore, only a few cysteine-targeting reagents enable the site-selective attachment of multiple functionalities: a useful tool in the fields of theranostics and therapeutic blood half-life extension. Herein, we demonstrate the application of the pyridazinedione motif to enable site-selective attachment of three functionalities to a protein bearing a single cysteine residue. Extending upon previously documented dual modification work, here we demonstrate that by exploiting a bromide leaving group as an additional reactive point on the pyridazinedione scaffold, a thiol or aniline derivative can be added to a protein, post-conjugation. Thiol cleavability appraisal of the resultant C–S and C–N linked thio-bioconjugates demonstrated C–S functionalized linkers to be cleavable and C–N functionalized linkers to be noncleavable when incubated in an excess of glutathione. The plug-and-play trifunctional platform was exemplified by attaching clinically relevant motifs: biotin, fluorescein, a polyethylene glycol chain, and a model peptide. This platform provides a rare opportunity to combine up to three functionalities on a protein in a site-selective fashion. Furthermore, by selecting the use of a thiol or an amine for functionalization, we provide unique control over linker cleavability toward thiols, allowing this novel linker to be applied in a range of physiological environments
Edging your bets: advantage play, gambling, crime and victimisation
Consumerism, industrial development and regulatory liberalisation have underpinned the ascendance of gambling to a mainstream consumption practice. In particular, the online gambling environment has been marketed as a site of ‘safe risks’ where citizens can engage in a multitude of different forms of aleatory consumption. This paper offers a virtual ethnography of an online ‘advantage play’ subculture. It demonstrates how advantage players have reinterpreted the online gambling landscape as an environment saturated with crime and victimisation. In this virtual world, advantage play is no longer simply an instrumental act concerned with profit accumulation to finance consumer desires. Rather, it acts as an opportunity for individuals to engage in a unique form of edgework, whereby the threat to one’s well-being is tested through an ability to avoid crime and victimisation. This paper demonstrates how mediated environments may act as sites for edgeworking and how the potential for victimisation can be something that is actively engaged with
Cardiac magnetic resonance imaging analysis in STEMI: quantitative or still visual?
Cardiovascular Aspects of Radiolog
Review and update the UK agriculture MACC to assess the abatement potential for the 5th carbon budget period and to 2050:Final report submitted for the project contract “Provision of services to review and update the UK agriculture MACC and to assess abatement potential for the 5th carbon budget period and to 2050”
Bibliometrics of systematic reviews : analysis of citation rates and journal impact factors
Background:
Systematic reviews are important for informing clinical practice and health policy. The aim of this study was to examine the bibliometrics of systematic reviews and to determine the amount of variance in citations predicted by the journal impact factor (JIF) alone and combined with several other characteristics.
Methods:
We conducted a bibliometric analysis of 1,261 systematic reviews published in 2008 and the citations to them in the Scopus database from 2008 to June 2012. Potential predictors of the citation impact of the reviews were examined using descriptive, univariate and multiple regression analysis.
Results:
The mean number of citations per review over four years was 26.5 (SD +/-29.9) or 6.6 citations per review per year. The mean JIF of the journals in which the reviews were published was 4.3 (SD +/-4.2). We found that 17% of the reviews accounted for 50% of the total citations and 1.6% of the reviews were not cited. The number of authors was correlated with the number of citations (r = 0.215, P =5.16) received citations in the bottom quartile (eight or fewer), whereas 9% of reviews published in the lowest JIF quartile (<=2.06) received citations in the top quartile (34 or more). Six percent of reviews in journals with no JIF were also in the first quartile of citations.
Conclusions:
The JIF predicted over half of the variation in citations to the systematic reviews. However, the distribution of citations was markedly skewed. Some reviews in journals with low JIFs were well-cited and others in higher JIF journals received relatively few citations; hence the JIF did not accurately represent the number of citations to individual systematic reviews
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