461 research outputs found

    Discovery of a redshift 6.13 quasar in the UKIRT infrared deep sky survey

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    Original article can be found at: http://www.aanda.org/ Copyright The European Southern Observatory (ESO) DOI: 10.1051/0004-6361/200811161Optical and near-infrared (NIR) spectra are presented for ULAS J131911.29+095051.4 (hereafter ULAS J1319+0950), a new redshift z = 6.127 0.004 quasar discovered in the Third Data Release (DR3) of the UKIRT Infrared Deep Sky Survey (UKIDSS). The source has = 19.10 0.03, corresponding to = -27.12, which is comparable to the absolute magnitudes of the z 6 quasars discovered in the Sloan Digital Sky Survey (SDSS). ULAS J1319+0950 was, in fact, registered by SDSS as a faint source with = 20.13 0.12, just below the signal-to-noise ratio limit of the SDSS high-redshift quasar survey. The faint z-band magnitude is a consequence of the weak Ly /N V emission line, which has a rest-frame equivalent width of ~20Å and provides only a small boost to the z-band flux. Nevertheless, there is no evidence of a significant new population of high-redshift quasars with weak emission lines from this UKIDSS-based search. The Ly  optical depth to ULAS J1319+0950 is consistent with that measured towards similarly distant SDSS quasars, implying that results from optical- and NIR-selected quasars may be combined in studies of cosmological reionization. Also presented is a new NIR-spectrum of the previously discovered UKIDSS quasar ULAS J020332.38+001229.2, which reveals the object to be a broad absorption line quasar. The new spectrum shows that the emission line initially identified as Ly  is actually N V, leading to a revised redshift of z = 5.72, rather than z = 5.86 as previously estimatedPeer reviewe

    Effect of interventions incorporating personalised cancer risk information on intentions and behaviour: A systematic review and meta-analysis of randomised controlled trials

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    Objective To provide a comprehensive review of the impact on intention to change health-related behaviours and health-related behaviours themselves, including screening uptake, of interventions incorporating information about cancer risk targeted at the general adult population. Design A systematic review and random-effects meta-analysis. Data sources An electronic search of MEDLINE, EMBASE, CINAHL and PsycINFO from 1 January 2000 to 1 July 2017. Inclusion criteria Randomised controlled trials of interventions including provision of a personal estimate of future cancer risk based on two or more non-genetic variables to adults recruited from the general population that include at least one behavioural outcome. Results We included 19 studies reporting 12 outcomes. There was significant heterogeneity in interventions and outcomes between studies. There is evidence that interventions incorporating personalised cancer risk information do not affect intention to attend or attendance at screening (relative risk 1.00 (0.97-1.03)). There is limited evidence that they increase smoking abstinence, sun protection, adult skin self-examination and breast examination, and decrease intention to tan. However, they do not increase smoking cessation, parental child skin examination or intention to protect skin. No studies assessed changes in diet, alcohol consumption or physical activity. Conclusions Interventions incorporating personalised cancer risk information do not affect uptake of screening, but there is limited evidence of effect on some health-related behaviours. Further research, ideally including objective measures of behaviour, is needed before cancer risk information is incorporated into routine practice for health promotion in the general population. Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted

    Solution structure of the Hop TPR2A domain and investigation of target druggability by NMR, biochemical and in silico approaches

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    Heat shock protein 90 (Hsp90) is a molecular chaperone that plays an important role in tumour biology by promoting the stabilisation and activity of oncogenic ‘client’ proteins. Inhibition of Hsp90 by small-molecule drugs, acting via its ATP hydrolysis site, has shown promise as a molecularly targeted cancer therapy. Owing to the importance of Hop and other tetratricopeptide repeat (TPR)-containing cochaperones in regulating Hsp90 activity, the Hsp90-TPR domain interface is an alternative site for inhibitors, which could result in effects distinct from ATP site binders. The TPR binding site of Hsp90 cochaperones includes a shallow, positively charged groove that poses a significant challenge for druggability. Herein, we report the apo, solution-state structure of Hop TPR2A which enables this target for NMR-based screening approaches. We have designed prototype TPR ligands that mimic key native ‘carboxylate clamp’ interactions between Hsp90 and its TPR cochaperones and show that they block binding between Hop TPR2A and the Hsp90 C-terminal MEEVD peptide. We confirm direct TPR-binding of these ligands by mapping 1H–15N HSQC chemical shift perturbations to our new NMR structure. Our work provides a novel structure, a thorough assessment of druggability and robust screening approaches that may offer a potential route, albeit difficult, to address the chemically challenging nature of the Hop TPR2A target, with relevance to other TPR domain interactors

    Different in the prospective association between individual plasma phospholipid saturated fatty acids and incident type 2 diabetes: the EPIC-InterAct case-cohort study

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    Background Conflicting evidence exists regarding the association between saturated fatty acids (SFAs) and type 2 diabetes. In this longitudinal case-cohort study, we aimed to investigate the prospective associations between objectively measured individual plasma phospholipid SFAs and incident type 2 diabetes in EPIC-InterAct participants. Methods The EPIC-InterAct case-cohort study includes 12¿403 people with incident type 2 diabetes and a representative subcohort of 16¿154 individuals who were selected from a cohort of 340¿234 European participants with 3·99 million person-years of follow-up (the EPIC study). Incident type 2 diabetes was ascertained until Dec 31, 2007, by a review of several sources of evidence. Gas chromatography was used to measure the distribution of fatty acids in plasma phospholipids (mol%); samples from people with type 2 diabetes and subcohort participants were processed in a random order by centre, and laboratory staff were masked to participant characteristics. We estimated country-specific hazard ratios (HRs) for associations per SD of each SFA with incident type 2 diabetes using Prentice-weighted Cox regression, which is weighted for case-cohort sampling, and pooled our findings using random-effects meta-analysis. Findings SFAs accounted for 46% of total plasma phospholipid fatty acids. In adjusted analyses, different individual SFAs were associated with incident type 2 diabetes in opposing directions. Even-chain SFAs that were measured (14:0 [myristic acid], 16:0 [palmitic acid], and 18:0 [stearic acid]) were positively associated with incident type 2 diabetes (HR [95% CI] per SD difference: myristic acid 1·15 [95% CI 1·09–1·22], palmitic acid 1·26 [1·15–1·37], and stearic acid 1·06 [1·00–1·13]). By contrast, measured odd-chain SFAs (15:0 [pentadecanoic acid] and 17:0 [heptadecanoic acid]) were inversely associated with incident type 2 diabetes (HR [95% CI] per 1 SD difference: 0·79 [0·73–0·85] for pentadecanoic acid and 0·67 [0·63–0·71] for heptadecanoic acid), as were measured longer-chain SFAs (20:0 [arachidic acid], 22:0 [behenic acid], 23:0 [tricosanoic acid], and 24:0 [lignoceric acid]), with HRs ranging from 0·72 to 0·81 (95% CIs ranging between 0·61 and 0·92). Our findings were robust to a range of sensitivity analyses. Interpretation Different individual plasma phospholipid SFAs were associated with incident type 2 diabetes in opposite directions, which suggests that SFAs are not homogeneous in their effects. Our findings emphasise the importance of the recognition of subtypes of these fatty acids. An improved understanding of differences in sources of individual SFAs from dietary intake versus endogenous metabolism is needed. Funding EU FP6 programme, Medical Research Council Epidemiology Unit, Medical Research Council Human Nutrition Research, and Cambridge Lipidomics Biomarker Research Initiative

    Valence nucleon populations in the Ni isotopes

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    Measurements of neutron-adding, neutron-removing, and proton-adding reactions were carried out for the four stable even Ni isotopes. Particular attention was paid to obtaining precise values of the cross sections at the peaks of the angular distributions. Tests with sum rules for the neutron data indicate that the results are self-consistent at the level of a few tenths of a nucleon. Data on proton-adding reactions were also obtained and analyzed with a slightly different method—while these data are also consistent, the ambiguities are larger. The occupancies of the neutron orbits derived from the data, the proton vacancies, and the energy centroids of the neutron, neutron-hole, and proton single-particle excitations are obtained. The data also provide some estimate about the closure of the 0f7/2 shell. The results are compared to shell-model calculations and may serve as a reference point for future exploration

    Women, men and coronary heart disease: a review of the qualitative literature

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    Aim. This paper presents a review of the qualitative literature which examines the experiences of patients with coronary heart disease. The paper also assesses whether the experiences of both female and male patients are reflected in the literature and summarizes key themes. Background. Understanding patients' experiences of their illness is important for coronary heart disease prevention and education. Qualitative methods are particularly suited to eliciting patients' detailed understandings and perceptions of illness. As much previous research has been 'gender neutral', this review pays particular attention to gender. Methods. Published papers from 60 qualitative studies were identified for the review through searches in MEDLINE, EMBASE, CINAHL, PREMEDLINE, PsychINFO, Social Sciences Citation Index and Web of Science using keywords related to coronary heart disease. Findings. Early qualitative studies of patients with coronary heart disease were conducted almost exclusively with men, and tended to generalize from 'male' experience to 'human' experience. By the late 1990s this pattern had changed, with the majority of studies including women and many being conducted with solely female samples. However, many studies that include both male and female coronary heart disease patients still do not have a specific gender focus. Key themes in the literature include interpreting symptoms and seeking help, belief about coronary 'candidates' and relationships with health professionals. The influence of social roles is important: many female patients have difficulties reconciling family responsibilities and medical advice, while male patients worry about being absent from work. Conclusions. There is a need for studies that compare the experiences of men and women. There is also an urgent need for work that takes masculinity and gender roles into account when exploring the experiences of men with coronary heart disease

    Evolution of the nuclear spin-orbit splitting explored via the <sup>32</sup>Si<i>(d,p)</i><sup>33</sup>Si reaction using SOLARIS

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    The spin-orbit splitting between neutron 1p orbitals at 33Si has been deduced using the single-neutron-adding (d,p) reaction in inverse kinematics with a beam of 32Si, a long-lived radioisotope. Reaction products were analyzed by the newly implemented SOLARIS spectrometer at the reaccelerated-beam facility at the National Superconducting Cyclotron Laboratory. The measurements show reasonable agreement with shell-model calculations that incorporate modern cross-shell interactions, but they contradict the prediction of proton density depletion based on relativistic mean-field theory. The evolution of the neutron 1p-shell orbitals is systematically studied using the present and existing data in the isotonic chains of = 17, 19, and 21. In each case, a smooth decrease in the separation of the - orbitals is seen as the respective p-orbitals approach zero binding, suggesting that the finite nuclear potential strongly influences the evolution of nuclear structure in this region
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