APOE Genotype Modulates Proton Magnetic Resonance Spectroscopy Metabolites in the Aging Brain

Background: Proton magnetic resonance spectroscopy (H-1-MRS) studies on healthy aging have reported inconsistent findings and have not systematically taken into account the possible modulatory effect of APOE genotype. We aimed to quantify brain metabolite changes in healthy subjects in relation to age and the presence of the APOE E4 genetic risk factor for Alzheimer\u27s disease. Additionally, we examined these measures in relation to cognition. Methods: We studied a cohort of 112 normal adults between 50 and 86 years old who were genotyped for APOE genetic polymorphism. Measurements of H-1-MRS metabolites were obtained in the posterior cingulate and precuneus region. Measures of general cognitive functioning, memory, executive function, semantic fluency, and speed of processing were also obtained. Results: General linear model analysis demonstrated that older APOE E4 carriers had significantly higher choline/creatine and myoinositol/creatine ratios than APOE E3 homozygotes. Structural equation modeling resulted in a model with an excellent goodness of fit and in which the APOE x age interaction and APOE status each had a significant effect on H-1-MRS metabolites (choline/creatine and myo-inositol/creatine). Furthermore, the APOE x age variable modulation of cognition was mediated by H-1-MRS metabolites. Conclusions: In a healthy aging normal population, choline/creatine and myo-inositol/creatine ratios were significantly increased in APOE E4 carriers, suggesting the presence of neuroinflammatory processes and greater membrane turnover in older carriers. Structural equation modeling analysis confirmed these possible neurodegenerative markers and also indicated the mediator role of these metabolites on cognitive performance among older APOE E4 carriers

Witchcraft and the Somerset idyll : The depiction of folk belief in Walter Raymond’s novels

The work of Walter Raymond (1852-1931) is now largely forgotten. Yet his Somerset novels, complemented by his ethnographic writings, contain depictions of local witchcraft belief that are worthy of study in literary and historical contexts. They raise issues regarding the fictional depiction of rural life and tradition, and the value of fiction as a folkloric and historical sourcePeer reviewe

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

The effective width of branch plate to RHS chord connections in cross joints

Civil Engineering and GeosciencesStructural Engineerin

The effective width of branch crosswalls for RR joints in tension

Civil Engineering and GeosciencesStructural Engineerin

Open Data: Growing Up and Getting Specific

Open data has been given a lot of attention in the public. In some situation ‘open by default’ has become established as a core principle, whereas others argue about the limited results and the lack of robust studies demonstrating the value, and point to the risk that open data might turn out to be a short lived policy fad. This special issue contains a variety of research papers addressing this topic from different views and providing recent research results on open data. The papers in this issue deepen the understanding of open data and show that the subject of open data is moving from the general to the study of specifics. The special issue also includes invited papers presented at the first public meeting of the SharePSI project. Share-PSI 2.0 is the European network for the exchange of experience and ideas around implementing open data policies in the public sector.Engineering, Systems and ServicesTechnology, Policy and Managemen

Discovering Software License Constraints: Identifying a Binary’s Sources by Tracing Build Processes

With the current proliferation of open source software components, intellectual property in general, and copyright law in particular, has become a critical non-functional requirement for software systems. A key problem in license compliance engineering is that the legal constraints on a product depend on the licenses of all sources and other artifacts used to build it. The huge size of typical dependency graphs makes it infeasible to determine these constraints manually, while mistakes can expose software distributors to litigation. In this paper we show a generic method to reverse-engineer this information from the build processes of software products by tracing system calls (e.g., open) to determine the composition graph of sources and binaries involved in build processes. Results from an exploratory case study of seven open source systems, which allowed us to discover a licensing problem in a widely used open source package, suggest our method is highly effective.Software Computer TechnologyElectrical Engineering, Mathematics and Computer Scienc

Behavioral and physiological responses of weaned foals treated with equine appeasing pheromone

Weaning, particularly the widespread practice of abrupt separation of the mare and foal, has been shown to be a stressful event for horses. Physiological changes in foals measured after weaning include increased blood cortisol concentrations and a subsequent decrease in cell-mediated immune responses. In the randomized, double-blinded, placebo-controlled trial reported here, we assessed the effect of an equine appeasing pheromone (EAP; Modipher EQ, E.A.P. Mist [Pherosynthese s.n.c., Le Rieu Neuf, Saint-Saturnin-les-Apt, France]) as an aid for reducing the behavioral and physiological signs of stress during weaning. Fourteen quarter horse foals were separated from their dam (equid mother) between 105 and 146 days of age, in age-matched pairs, and placed in 3.66 × 3.66 m stalls (one treated and one control foal in each stall). Treated foals received the synthetic analogue of the EAP by intranasal wipe 30 minutes before separation and twice daily thereafter for 48 hours. Control foals received placebo by intranasal wipe on the same schedule. The foals were continuously videotaped for 48 hours postweaning to monitor behavioral responses. Blood samples were drawn 24 hours pretreatment and 24 and 48 hours postweaning for evaluation of physiological indicators of stress (serum cortisol) and cytokines as stress-related and immune-mediated response parameters. Interestingly, although behavioral and serum cortisol measures were similar between groups, treatment with EAP had a significant (P < 0.05) effect on interleukin 6 and transforming growth factor β, whereas monocyte opiate receptor 1 was significantly upregulated in both groups independent of treatment when compared with baseline values. Although the link between EAP treatment and activation of the measured cytokines remains unexplained, our findings suggest immune-related gene transcription focused on the acute causes of stress in a time frame shortly after weaning

New insights into the complex photoluminescence behaviour of titanium white pigments

This work reports the analysis of the time-resolved photoluminescence behaviour on the nanosecond and microsecond time scale of fourteen historical and contemporary titanium white pigments. The pigments were produced with different production methods and post-production treatments, giving rise to a remarkable variability of titanium dioxide powders and, in some cases, to the formation of a complex surface of the crystal agglomerates. The pigments have been further characterized by Raman spectroscopy, scanning transmission electron microscopy coupled with energy dispersive X-ray spectroscopy and inductively coupled plasma atomic emission spectrometry. Our study provides a clear view of the main features of the photoluminescence (PL) emission of anatase- and rutile-based pigments. For both the polymorphs of titanium dioxide the room-temperature photoluminescence emission is complex and involves different relaxation paths, related to shallow levels close to the conduction bands and mid-gap trap states. The PL behaviour appears to be little affected by post-production treatments such as organic and inorganic coatings. Instead, the presence of niobium impurities in the TiO2 crystal lattice, as residues of the sulphate synthesis process, induce a remarkable quenching of the visible emission of anatase-based pigments. We confirm that rutile-based and anatase-based pigments are significantly different in terms of photoluminescence behaviour. This clear distinction is a valuable point for non-invasive pigment identification by in-situ photoluminescence spectroscopy. In particular, while many organic binding media emit in the visible region, the near-infrared emission of rutile is specific and can likely be used to identify the pigment in more complex materials as paints. This research paves the way to future studies of the photo-physical properties of titanium white pigments, which is imperative to understand the risk of degradation induced by the well-known photocatalytic activity of this widely used 20th century pigment.Accepted Author Manuscript(OLD) MSE-