Thermodynamics and defect chemistry of substitutional and interstitial cation doping in layered α-V2O5

A systematic study of the location and energetics of cation dopants in α-V2O5 has been conducted using pair-potential methods, supplemented by first-principles calculations. The consequences of doping on intrinsic defect equilibria have been discussed and the effects of selected dopants on Li+ and Mg2+ diffusion energy barriers have been investigated

Energy storage mechanisms in vacancy-ordered Wadsley-Roth layered niobates

Wadsley–Roth (WR) crystallographic shear structures demonstrate high energy and power densities as Li-ion battery anode materials. We report the (de)lithiation behavior of two WR-derived layered niobates: NaNb_{3}O_{8} and KNb_{3}O_{8}. Both demonstrate multi-electron (Nb5+/Nb3+) redox on the first discharge, reacting with ≈5 mol Li per mol ANb_{3}O_{8}. Li intercalation in NaNb_{3}O_{8} is dominated by Li-diffusion kinetics and evolution of the interlayer structure, with Li initially filling octahedral sites near the interlayer space to draw the layers together to form a (2 × 2)_{∞} WR structure. This average structure change pushes Na ions into the square channels, blocking fast Li diffusion down the square channels that provide the fast Li-ion conduction in most WR materials. Upon charge, Li ions incorporated into the octahedral WR sites (ordered vacancies in the layered structure) are extracted, revealing a new, reversible Li site for additional capacity in WR-like materials. The behavior of KNb_{3}O_{8} is similar, but has additional hysteresis associated with its larger counter-cation. While neither layered niobate matches the demonstrated performance of WR materials, by studying them, we identify a route for increased capacity in WR-like frameworks. Additionally, we identify the important role of Li diffusion kinetics and counter-cations in the cycling behavior of WR-derived structures

PI3Kgamma drives priming and survival of autoreactive CD4(+) T cells during experimental autoimmune encephalomyelitis

The class IB phosphoinositide 3-kinase γ enzyme complex (PI3Kc) functions in multiple signaling pathways involved in leukocyte activation and migration, making it an attractive target in complex human inflammatory diseases including MS. Here, using pik3cg2/2 mice and a selective PI3Kc inhibitor, we show that PI3Kc promotes development of experimental autoimmune encephalomyelitis (EAE). In pik3cg2/2 mice, EAE is markedly suppressed and fewer leukocytes including CD4+ and CD8+ T cells, granulocytes and mononuclear phagocytes infiltrate the CNS. CD4+ T cell priming in secondary lymphoid organs is reduced in pik3cg2/2 mice following immunisation. This is attributable to defects in DC migration concomitant with a failure of full T cell activation following TCR ligation in the absence of p110c. Together, this results in suppressed autoreactive T cell responses in pik3cg2/2 mice, with more CD4+ T cells undergoing apoptosis and fewer cytokineproducing Th1 and Th17 cells in lymphoid organs and the CNS. When administered from onset of EAE, the orally active PI3Kc inhibitor AS605240 caused inhibition and reversal of clinical disease, and demyelination and cellular pathology in the CNS was reduced. These results strongly suggest that inhibitors of PI3Kc may be useful therapeutics for MS.Iain Comerford, Wendel Litchfield, Ervin Kara and Shaun R. McCol

Analysis of the platypus genome suggests a transposon origin for mammalian imprinting

Comparisons between the platypus and eutherian mammalian genomes provides new insights into how epigenetic imprinting may have evolved in mammalian genomes

In vivo dual RNA-seq reveals that neutrophil recruitment underlies differential tissue tropism of Streptococcus pneumoniae.

Streptococcus pneumoniae is a genetically diverse human-adapted pathogen commonly carried asymptomatically in the nasopharynx. We have recently shown that a single nucleotide polymorphism (SNP) in the raffinose pathway regulatory gene rafR accounts for a difference in the capacity of clonally-related strains to cause localised versus systemic infection. Using dual RNA-seq, we show that this SNP affects expression of bacterial genes encoding multiple sugar transporters, and fine-tunes carbohydrate metabolism, along with extensive rewiring of host transcriptional responses to infection, particularly expression of genes encoding cytokine and chemokine ligands and receptors. The data predict a crucial role for differential neutrophil recruitment (confirmed by in vivo neutrophil depletion and IL-17 neutralization) indicating that early detection of bacteria by the host in the lung environment is crucial for effective clearance. Thus, dual RNA-seq provides a powerful tool for understanding complex host-pathogen interactions and reveals how a single bacterial SNP can drive differential disease outcomes

Meaning behind measurement : self-comparisons affect responses to health related quality of life questionnaires

Purpose The subjective nature of quality of life is particularly pertinent to the domain of health-related quality of life (HRQOL) research. The extent to which participants’ responses are affected by subjective information and personal reference frames is unknown. This study investigated how an elderly population living with a chronic metabolic bone disorder evaluated self-reported quality of life. Methods Participants (n = 1,331) in a multi-centre randomised controlled trial for the treatment of Paget’s disease completed annual HRQOL questionnaires, including the SF-36, EQ-5D and HAQ. Supplementary questions were added to reveal implicit reference frames used when making HRQOL evaluations. Twenty-one participants (11 male, 10 female, aged 59–91 years) were interviewed retrospectively about their responses to the supplementary questions, using cognitive interviewing techniques and semi-structured topic guides. Results The interviews revealed that participants used complex and interconnected reference frames to promote response shift when making quality of life evaluations. The choice of reference frame often reflected external factors unrelated to individual health. Many participants also stated that they were unclear whether to report general or disease-related HRQOL. Conclusions It is important, especially in clinical trials, to provide instructions clarifying whether ‘quality of life’ refers to disease-related HRQOL. Information on selfcomparison reference frames is necessary for the interpretation of responses to questions about HRQOL.The Chief Scientist Office of the Scottish Government Health Directorates, The PRISM funding bodies (the Arthritis Research Campaign, the National Association for the Relief of Paget’s disease and the Alliance for Better Bone Health)Peer reviewedAuthor final versio

The nature of weather and climate impacts in the energy sector

The power sector’s meteorological information needs are diverse and cover many different distinct applications and users. Recognising this diversity, it is important to understand the general nature of how weather and climate influence the energy sector and the implications they have for quantitative impact modelling. Using conceptual examples and illustrations from recent research, this chapter argues that the traditional ‘transfer function’ approach that is common to many industrial applications of weather and climate science—whereby weather can be directly mapped to an energy impact—is inadequate for many important power system applications (such as price forecasting and system operations and planning). The chapter concludes by arguing that a deeper understanding of how meteorological impacts in the energy sector are modelled is required