Forecasting scenarios for UK household expenditure and associated GHG emissions : Outlook to 2030

Peer reviewedPreprin

Microwave absorption and radiation from large-area multilayer CVD graphene

Here we experimentally study the microwave absorption and near-field radiation behaviour of monolayer and few-layer, large-area CVD graphene in the C and X bands. Artificial stacking of CVD graphene reduces the sheet resistance, as verified by non-contact microwave cavity measurements and four-probe DC resistivity. The proposed multilayer stacked graphene exhibits increased absorption determined by the total sheet resistance. The underlying mechanism could enable us to apply nanoscale graphene sheets as optically transparent radar absorbers. Near-field radiation measurements show that our present few-layer graphene patches with sheet resistance more than 600 /sq exhibit no distinctive microwave resonance and radiate less electromagnetic power with increasing layers; however, our theoretical prediction suggests that for samples to be significant as microwave antennas, doped multilayer graphene with sheet resistance less than 10 /sq is required.This work was funded by the Graphene Research Centre, University of Cambridge, and the Engineering and Physical Sciences Research Council (EPSRC), UK under a Program Grant (EP/K01711X/1). M.T.C thanks the Winston Churchill Trust and the International Young Scientist Research Fellowship, National Natural Science Foundation of China, for generous financial support. B.W. acknowledges the fund support from the China Scholarship Council and National Natural Science Foundation of China No. 61271017.This is the FINAL published version, also available on the publisher's website at: http://www.sciencedirect.com/science/article/pii/S000862231400540

Knowledge generation about care-giving in the UK: a critical review of research paradigms

While discourse about care and caring is well developed in the UK, the nature of knowledge generation about care and the research paradigms that underpin it have been subjected to limited critical reflection and analysis. An overarching synthesis of evidence – intended to promote debate and facilitate new understandings – identifies two largely separate bodies of carer-related research. The first body of work – referred to as Gathering and Evaluating – provides evidence of the extent of caregiving, who provides care to whom and with what impact; it also focuses on evaluating policy and service efficacy. This type of research tends to dominate public perception about caring, influences the type and extent of policy and support for carers and attracts funding from policy and health-related sources. However, it also tends to be conceptually and theoretically narrow, has limited engagement with carers’ perspectives and adopts an atomistic purview on the care-giving landscape. The second body of work – Conceptualising and Theorising – explores the conceptual and experiential nature of care and aims to extend thinking and theory about caring. It is concerned with promoting understanding of care as an integral part of human relationships, embedded in the life course, and a product of interdependence and reciprocity. This work conceptualises care as both an activity and a disposition and foregrounds the development of an ‘ethic of care’, thereby providing a perspective within which to recognise both the challenges care-giving may present and the significance of care as a normative activity. It tends to be funded from social science sources and, while strong in capturing carers’ experiences, has limited policy and service-related purchase. Much could be gained for citizens, carers and families, and the generation of knowledge advanced, if the two bodies of research were integrated to a greater degree

Delayed Toxicity Associated with Soluble Anthrax Toxin Receptor Decoy-Ig Fusion Protein Treatment

Soluble receptor decoy inhibitors, including receptor-immunogloubulin (Ig) fusion proteins, have shown promise as candidate anthrax toxin therapeutics. These agents act by binding to the receptor-interaction site on the protective antigen (PA) toxin subunit, thereby blocking toxin binding to cell surface receptors. Here we have made the surprising observation that co-administration of receptor decoy-Ig fusion proteins significantly delayed, but did not protect, rats challenged with anthrax lethal toxin. The delayed toxicity was associated with the in vivo assembly of a long-lived complex comprised of anthrax lethal toxin and the receptor decoy-Ig inhibitor. Intoxication in this system presumably results from the slow dissociation of the toxin complex from the inhibitor following their prolonged circulation. We conclude that while receptor decoy-Ig proteins represent promising candidates for the early treatment of B. anthracis infection, they may not be suitable for therapeutic use at later stages when fatal levels of toxin have already accumulated in the bloodstream

Evidence against a Human Cell-Specific Role for LRP6 in Anthrax Toxin Entry

The role of the cellular protein LRP6 in anthrax toxin entry is controversial. Previous studies showed that LRP6 was important for efficient intoxication of human M2182 prostate carcinoma cells but other studies performed with cells from gene-knockout mice demonstrated no role for either LRP6 or the related LRP5 protein in anthrax toxin entry. One possible explanation for this discrepancy is that LRP6 may be important for anthrax toxin entry into human, but not mouse, cells. To test this idea we have investigated the effect of knocking down LRP6 or LRP5 expression with siRNAs in human HeLa cells. We show here that efficient knockdown of either LRP6, LRP5, or both proteins has no influence on the kinetics of anthrax lethal toxin entry or MEK1 substrate cleavage in these cells. These data argue against a human-specific role for LRP6 in anthrax toxin entry and suggest instead that involvement of this protein may be restricted to certain cell types independently of their species of origin

Anthrax Toxin Receptor 2 Determinants that Dictate the pH Threshold of Toxin Pore Formation

The anthrax toxin receptors, ANTXR1 and ANTXR2, act as molecular clamps to prevent the protective antigen (PA) toxin subunit from forming pores until exposure to low pH. PA forms pores at pH ∼6.0 or below when it is bound to ANTXR1, but only at pH ∼5.0 or below when it is bound to ANTXR2. Here, structure-based mutagenesis was used to identify non-conserved ANTXR2 residues responsible for this striking 1.0 pH unit difference in pH threshold. Residues conserved between ANTXR2 and ANTXR1 that influence the ANTXR2-associated pH threshold of pore formation were also identified. All of these residues contact either PA domain 2 or the neighboring edge of PA domain 4. These results provide genetic evidence for receptor release of these regions of PA as being necessary for the protein rearrangements that accompany anthrax toxin pore formation

Cross-examination: The Testimony of Children With and Without Intellectual Disabilities

The present study assessed how children with a range of cognitive abilities fared during a mock cross-examination. Ninety children (aged 4 to 11 years; 18 with intellectual disabilities [ID], 13 with borderline intellectual disabilities [BID], and 59 who were typically developing [TD]) witnessed a staged event, participated in an initial forensic interview (a few days later), and were cross-examined by a barrister-in-training (ten months later). During cross-examination, 98% of all children changed at least one response from their initial interview when challenged. However, group differences in performance (total number of changed responses, ‘resistance’ to challenges), controlling for age and memory for event details, were not significant or did not prove reliable at the level of individual group contrasts. Overall, little robust evidence for group differences in performance on crossexamination could be identified, and memory for event details was the most reliable predictor of performance

Computing H/D-Exchange rates of single residues from data of proteolytic fragments

<p>Abstract</p> <p>Background</p> <p>Protein conformation and protein/protein interaction can be elucidated by solution-phase Hydrogen/Deuterium exchange (sHDX) coupled to high-resolution mass analysis of the digested protein or protein complex. In sHDX experiments mutant proteins are compared to wild-type proteins or a ligand is added to the protein and compared to the wild-type protein (or mutant). The number of deuteriums incorporated into the polypeptides generated from the protease digest of the protein is related to the solvent accessibility of amide protons within the original protein construct.</p> <p>Results</p> <p>In this work, sHDX data was collected on a 14.5 T FT-ICR MS. An algorithm was developed based on combinatorial optimization that predicts deuterium exchange with high spatial resolution based on the sHDX data of overlapping proteolytic fragments. Often the algorithm assigns deuterium exchange with single residue resolution.</p> <p>Conclusions</p> <p>With our new method it is possible to automatically determine deuterium exchange with higher spatial resolution than the level of digested fragments.</p

The Epstein-Barr Virus G-Protein-Coupled Receptor Contributes to Immune Evasion by Targeting MHC Class I Molecules for Degradation

Epstein-Barr virus (EBV) is a human herpesvirus that persists as a largely subclinical infection in the vast majority of adults worldwide. Recent evidence indicates that an important component of the persistence strategy involves active interference with the MHC class I antigen processing pathway during the lytic replication cycle. We have now identified a novel role for the lytic cycle gene, BILF1, which encodes a glycoprotein with the properties of a constitutive signaling G-protein-coupled receptor (GPCR). BILF1 reduced the levels of MHC class I at the cell surface and inhibited CD8+ T cell recognition of endogenous target antigens. The underlying mechanism involves physical association of BILF1 with MHC class I molecules, an increased turnover from the cell surface, and enhanced degradation via lysosomal proteases. The BILF1 protein of the closely related CeHV15 c1-herpesvirus of the Rhesus Old World primate (80% amino acid sequence identity) downregulated surface MHC class I similarly to EBV BILF1. Amongst the human herpesviruses, the GPCR encoded by the ORF74 of the KSHV c2-herpesvirus is most closely related to EBV BILF1 (15% amino acid sequence identity) but did not affect levels of surface MHC class I. An engineered mutant of BILF1 that was unable to activate G protein signaling pathways retained the ability to downregulate MHC class I, indicating that the immune-modulating and GPCR-signaling properties are two distinct functions of BILF1. These findings extend our understanding of the normal biology of an important human pathogen. The discovery of a third EBV lytic cycle gene that cooperates to interfere with MHC class I antigen processing underscores the importance of the need for EBV to be able to evade CD8+ T cell responses during the lytic replication cycle, at a time when such a large number of potential viral targets are expressed

Options for early breast cancer follow-up in primary and secondary care : a systematic review

Background Both incidence of breast cancer and survival have increased in recent years and there is a need to review follow up strategies. This study aims to assess the evidence for benefits of follow-up in different settings for women who have had treatment for early breast cancer. Method A systematic review to identify key criteria for follow up and then address research questions. Key criteria were: 1) Risk of second breast cancer over time - incidence compared to general population. 2) Incidence and method of detection of local recurrence and second ipsi and contra-lateral breast cancer. 3) Level 1–4 evidence of the benefits of hospital or alternative setting follow-up for survival and well-being. Data sources to identify criteria were MEDLINE, EMBASE, AMED, CINAHL, PSYCHINFO, ZETOC, Health Management Information Consortium, Science Direct. For the systematic review to address research questions searches were performed using MEDLINE (2011). Studies included were population studies using cancer registry data for incidence of new cancers, cohort studies with long term follow up for recurrence and detection of new primaries and RCTs not restricted to special populations for trials of alternative follow up and lifestyle interventions. Results Women who have had breast cancer have an increased risk of a second primary breast cancer for at least 20 years compared to the general population. Mammographically detected local recurrences or those detected by women themselves gave better survival than those detected by clinical examination. Follow up in alternative settings to the specialist clinic is acceptable to women but trials are underpowered for survival. Conclusions Long term support, surveillance mammography and fast access to medical treatment at point of need may be better than hospital based surveillance limited to five years but further large, randomised controlled trials are needed