5MW Power Upgrade Studies of the ISIS TS1 Target

The increasing demand for neutron production at the ISIS neutron spallation source has motivated a study of an upgrade of the production target TS1. This study focuses on a 5 MW power upgrade and complete redesign of the ISIS TS1 spallation target, reflector and neutron moderators. The optimisation of the target-moderator arrangement was done in order to obtain the maximum neutron output per unit input power. In addition, at each step of this optimisation study, the heat load and thermal stresses were calculated to ensure the target can sustain the increase in the beam power

Macrophage coordination of the interferon lambda immune response

Lambda interferons (IFN-λs) are a major component of the innate immune defense to viruses, bacteria, and fungi. In human liver, IFN-λ not only drives antiviral responses, but also promotes inflammation and fibrosis in viral and non-viral diseases. Here we demonstrate that macrophages are primary responders to IFN-λ, uniquely positioned to bridge the gap between IFN-λ producing cells and lymphocyte populations that are not intrinsically responsive to IFN-λ. While CD14+ monocytes do not express the IFN-λ receptor, IFNLR1, sensitivity is quickly gained upon differentiation to macrophages in vitro. IFN-λ stimulates macrophage cytotoxicity and phagocytosis as well as the secretion of pro-inflammatory cytokines and interferon stimulated genes that mediate immune cell chemotaxis and effector functions. In particular, IFN-λ induced CCR5 and CXCR3 chemokines, stimulating T and NK cell migration, as well as subsequent NK cell cytotoxicity. Using immunofluorescence and cell sorting techniques, we confirmed that human liver macrophages expressing CD14 and CD68 are highly responsive to IFN-λ ex vivo. Together, these data highlight a novel role for macrophages in shaping IFN-λ dependent immune responses both directly through pro-inflammatory activity and indirectly by recruiting and activating IFN-λ unresponsive lymphocytes

The XMM Cluster Survey: The interplay between the brightest cluster galaxy and the intra-cluster medium via AGN feedback

Using a sample of 123 X-ray clusters and groups drawn from the XMM-Cluster Survey first data release, we investigate the interplay between the brightest cluster galaxy (BCG), its black hole, and the intra-cluster/group medium (ICM). It appears that for groups and clusters with a BCG likely to host significant AGN feedback, gas cooling dominates in those with Tx > 2 keV while AGN feedback dominates below. This may be understood through the sub-unity exponent found in the scaling relation we derive between the BCG mass and cluster mass over the halo mass range 10^13 < M500 < 10^15Msol and the lack of correlation between radio luminosity and cluster mass, such that BCG AGN in groups can have relatively more energetic influence on the ICM. The Lx - Tx relation for systems with the most massive BCGs, or those with BCGs co-located with the peak of the ICM emission, is steeper than that for those with the least massive and most offset, which instead follows self-similarity. This is evidence that a combination of central gas cooling and powerful, well fuelled AGN causes the departure of the ICM from pure gravitational heating, with the steepened relation crossing self-similarity at Tx = 2 keV. Importantly, regardless of their black hole mass, BCGs are more likely to host radio-loud AGN if they are in a massive cluster (Tx > 2 keV) and again co-located with an effective fuel supply of dense, cooling gas. This demonstrates that the most massive black holes appear to know more about their host cluster than they do about their host galaxy. The results lead us to propose a physically motivated, empirical definition of 'cluster' and 'group', delineated at 2 keV.Comment: Accepted for publication in MNRAS - replaced to match corrected proo

Amyloid-like Fibrils from an α-Helical Transmembrane Protein

The propensity to misfold and self-assemble into stable aggregates is increasingly being recognized as a common feature of protein molecules. Our understanding of this phenomenon and of its links with human disease has improved substantially over the past two decades. Studies thus far, however, have been almost exclusively focused on cytosolic proteins, resulting in a lack of detailed information about the misfolding and aggregation of membrane proteins. As a consequence, although such proteins make up approximately 30% of the human proteome and have high propensities to aggregate, relatively little is known about the biophysical nature of their assemblies. To shed light on this issue, we have studied as a model system an archetypical representative of the ubiquitous major facilitator superfamily, the Escherichia coli lactose permease (LacY). By using a combination of established indicators of cross-β structure and morphology, including the amyloid diagnostic dye thioflavin-T, circular dichroism spectroscopy, Fourier transform infrared spectroscopy, X-ray fiber diffraction, and transmission electron microscopy, we show that LacY can form amyloid-like fibrils under destabilizing conditions. These results indicate that transmembrane α-helical proteins, similarly to cytosolic proteins, have the ability to adopt this generic state.We are grateful for the award of the Marie Curie Career Development Fellowship (K.S.) and for support of this work by a Wellcome Trust Programme Grant 094425/Z/10/Z (C.M.D. and M.V.) and by an ERC Advanced Grant (294342) (N.J.H., P.J.B.)

Measuring academic research impact: creating a citation profile using the conceptual framework for implementation fidelity as a case study

The “citation score” remains the most commonly-used measure of academic impact, but is also viewed as practically and conceptually limited. The aim of this case study was to test the feasibility of creating a “citation profile” for a single, frequently-cited methods paper, the author’s own publication on the conceptual framework for implementation fidelity. This was a proof-of-concept study that involved an analysis of the citations of a single publication. This analysis involved identifying all citing publications and recording, not only how many times the key paper was cited within each citing publication, but also within which sections of that publication (e.g. Background, Methods, Results etc.). Level of impact could be categorised as high, moderate or low. The key paper had been cited more than 400 times and had a high impact in 25 % of publications based on citation frequency within publications, i.e. the key paper was cited three or more times; and a low impact in 58 % of citing publications, i.e. the key paper was cited just once. There were 41 “high impact” publications based on location of the citations, of which 35 (85 %) were also categorised as high impact by frequency. These results suggest that it is both possible and straightforward to categorise the level of impact of a key paper based on its “citation profile”, i.e., the frequency with which the paper is cited within citing publications, thus adding depth and value to the citation metric

Renewable energy resource assessment

© The Author(s) 2019. Literature overview of published global and regional renewable energy potential estimates. This section provides definitions for different types of RE potentials and introduces a new category, the economic renewable energy potential in space constrained environments. The potential for utility scale solar and onshore wind in square kilometre and maximum possible installed capacity (in GW) are provided for 75 different regions. The results set the upper limits for the deployment of solar- and wind technologies for the development of the 2.0 °C and 1.5 °C energy pathways

Ribosomal protein S6 mRNA is a biomarker upregulated in multiple sclerosis, downregulated by interferon treatment, and affected by season

Background

The mitogenome of the bed bug Cimex lectularius (Hemiptera: Cimicidae)

We report the extraction of a bed bug mitogenome from high-throughput sequencing projects originally focused on the nuclear genome of Cimex lectularius. The assembled mitogenome has a similar AT nucleotide composition bias found in other insects. Phylogenetic analysis of all protein-coding genes indicates that C. lectularius is clearly a member of a paraphyletic Cimicomorpha clade within the Order Hemiptera

Measurement of the Vector and Tensor Asymmetries at Large Missing Momentum in Quasielastic (\u3cem\u3ee\u3c/em\u3e\u3csup\u3e→\u3c/sup\u3e,\u3cem\u3ee\u27p\u3c/em\u3e Electron Scattering from Deuterium

We report the measurement of the beam-vector and tensor asymmetries AVed and ATd in quasielastic (e→,e′p) electrodisintegration of the deuteron at the MIT-Bates Linear Accelerator Center up to missing momentum of 500  MeV/c. Data were collected simultaneously over a momentum transfer range 0.1 \u3c Q2 \u3c 0.5  (GeV/c)2 with the Bates Large Acceptance Spectrometer Toroid using an internal deuterium gas target polarized sequentially in both vector and tensor states. The data are compared with calculations. The beam-vector asymmetry AVed is found to be directly sensitive to the D-wave component of the deuteron and has a zero crossing at a missing momentum of about 320  MeV/c, as predicted. The tensor asymmetry ATd at large missing momentum is found to be dominated by the influence of the tensor force in the neutron-proton final-state interaction. The new data provide a strong constraint on theoretical models

Quality indicators for systemic anticancer therapy services: a systematic review of metrics used to compare quality across healthcare facilities.

PURPOSE: The number of systemic anticancer therapy (SACT) regimens has expanded rapidly over the last decade. There is a need to ensure quality of SACT delivery across cancer services and systems in different resource settings to reduce morbidity, mortality, and detrimental economic impact at individual and systems level. Existing literature on SACT focuses on treatment efficacy with few studies on quality or how SACT is delivered within routine care in comparison to radiation and surgical oncology. METHODS: Systematic review was conducted following PRISMA guidelines. EMBASE and MEDLINE were searched and handsearching was undertaken to identify literature on existing quality indicators (QIs) that detect meaningful variations in the quality of SACT delivery across different healthcare facilities, regions, or countries. Data extraction was undertaken by two independent reviewers. RESULTS: This review identified 63 distinct QIs from 15 papers. The majority were process QIs (n = 55, 87.3%) relating to appropriateness of treatment and guideline adherence (n = 28, 44.4%). There were few outcome QIs (n = 7, 11.1%) and only one structural QI (n = 1, 1.6%). Included studies solely focused on breast, colorectal, lung, and skin cancer. All but one studies were conducted in high-income countries. CONCLUSIONS: The results of this review highlight a significant lack of research on SACT QIs particularly those appropriate for resource-constrained settings in low- and middle-income countries. This review should form the basis for future work in transforming performance measurement of SACT provision, through context-specific QI SACT development, validation, and implementation