Nrt1 and Tna1-Independent Export of NAD+ Precursor Vitamins Promotes NAD+ Homeostasis and Allows Engineering of Vitamin Production

NAD+ is both a co-enzyme for hydride transfer enzymes and a substrate of sirtuins and other NAD+ consuming enzymes. NAD+ biosynthesis is required for two different regimens that extend lifespan in yeast. NAD+ is synthesized from tryptophan and the three vitamin precursors of NAD+: nicotinic acid, nicotinamide and nicotinamide riboside. Supplementation of yeast cells with NAD+ precursors increases intracellular NAD+ levels and extends replicative lifespan. Here we show that both nicotinamide riboside and nicotinic acid are not only vitamins but are also exported metabolites. We found that the deletion of the nicotinamide riboside transporter, Nrt1, leads to increased export of nicotinamide riboside. This discovery was exploited to engineer a strain to produce high levels of extracellular nicotinamide riboside, which was recovered in purified form. We further demonstrate that extracellular nicotinamide is readily converted to extracellular nicotinic acid in a manner that requires intracellular nicotinamidase activity. Like nicotinamide riboside, export of nicotinic acid is elevated by the deletion of the nicotinic acid transporter, Tna1. The data indicate that NAD+ metabolism has a critical extracellular element in the yeast system and suggest that cells regulate intracellular NAD+ metabolism by balancing import and export of NAD+ precursor vitamins

Very high upper critical fields in MgB2 produced by selective tuning of impurity scattering

We report a significant enhancement of the upper critical field $H_{c2}$ of different $MgB_2$ samples alloyed with nonmagnetic impurities. By studying films and bulk polycrystals with different resistivities $\rho$, we show a clear trend of $H_{c2}$ increase as $\rho$ increases. One particular high resistivity film had zero-temperature $H_{c2}(0)$ well above the $H_{c2}$ values of competing non-cuprate superconductors such as $Nb_3Sn$ and Nb-Ti. Our high-field transport measurements give record values $H_{c2}^\perp (0) \approx 34T$ and $H_{c2}\|(0) \approx 49 T$ for high resistivity films and $H_{c2}(0)\approx 29 T$ for untextured bulk polycrystals. The highest $H_{c2}$ film also exhibits a significant upward curvature of $H_{c2}(T)$, and temperature dependence of the anisotropy parameter $\gamma(T) = H_{c2}\|/ H_{c2}^\perp$ opposite to that of single crystals: $\gamma(T)$ decreases as the temperature decreases, from $\gamma(T_c) \approx 2$ to $\gamma(0) \approx 1.5$. This remarkable $H_{c2}$ enhancement and its anomalous temperature dependence are a consequence of the two-gap superconductivity in $MgB_2$, which offers special opportunities for further $H_{c2}$ increase by tuning of the impurity scattering by selective alloying on Mg and B sites. Our experimental results can be explained by a theory of two-gap superconductivity in the dirty limit. The very high values of $H_{c2}(T)$ observed suggest that $MgB_2$ can be made into a versatile, competitive high-field superconductor.Comment: An updated version of the paper (12/12/2002)that was placed on cond-mat on May 7 200

The Middle Way: East Asian masters students’ perceptions of critical argumentation in U.K. universities.

The paper explores the learning experiences of East Asian masters students in dealing with Western academic norms of critical thinking in classroom debate and assignment writing. The research takes a cultural approach, and employs grounded theory and case study methodology, the aims being for students to explain their perceptions of their personal learning journeys. The data suggest that the majority of students interviewed rejected full academic acculturation into Western norms of argumentation. They instead opted for a ‘Middle Way’ that synergizes the traditional cultural academic values held by many East Asian students with those elements of Western academic norms that are perceived to be aligned with these. This is a relatively new area of research which represents a challenge for British lecturers and students

Strange Meson Enhancement in PbPb Collisions

The NA44 Collaboration has measured yields and differential distributions of K+, K-, pi+, pi- in transverse kinetic energy and rapidity, around the center-of-mass rapidity in 158 A GeV/c Pb+Pb collisions at the CERN SPS. A considerable enhancement of K+ production per pi is observed, as compared to p+p collisions at this energy. To illustrate the importance of secondary hadron rescattering as an enhancement mechanism, we compare strangeness production at the SPS and AGS with predictions of the transport model RQMD.Comment: 11 pages, including 4 figures, LATE

Informed design of educational technology for teaching and learning? Towards an evidence-informed model of good practice

The aim of this paper is to model evidence-informed design based on a selective critical analysis of research articles. We draw upon findings from an investigation into practitioners’ use of educational technologies to synthesise and model what informs their designs. We found that practitioners’ designs were often driven by implicit assumptions about learning. These shaped both the design of interventions and the methods sought to derive evaluations and interpret the findings. We argue that interventions need to be grounded in better and explicit conceptualisations of what constitutes learning in order to have well-informed designs that focus on improving the quality of student learning

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

Collaborative working in health and social care: Lessons learned from post‐hoc preliminary findings of a young families’ pregnancy to age 2 project in South Wales, United Kingdom

Children of young and socially disadvantaged parents are more likely to experience adverse outcomes. In response to this, a unique young families’ project in Swansea, UK, was created, which drew together a team of multi-agency professionals, to support people aged 16–24 from 17 weeks of pregnancy throughout 1,001 days of the child's life. The aim of the JIGSO (the Welsh word for Jigsaw) project is for young people to reach their potential as parents and to break the cycle of health and social inequality. This evaluation analysed routinely collected data held by the project from January 2017 to December 2018 exploring health and social outcomes, including smoking and alcohol use in pregnancy, breastfeeding, maternal diet and social services outcomes. Outcomes were compared to local and national averages, where available. Data relating to parenting knowledge and skills were available via records of 10-point Likert scales, one collected at the start of the JIGSO involvement and one around 4–6 months later. Findings showed higher than average levels of breastfeeding initiation and lower smoking and alcohol use in pregnancy. Parents also reported enhanced knowledge and confidence in their child care skills, as well as improved family relationships. Parents with high levels of engagement with JIGSO also appeared to have positive outcomes with Social Services (their child's name was removed from child protection register or their case was closed to social services). This was a post-hoc evaluation, not an intervention study or trial, and thus findings must be interpreted with caution. Despite this, the findings are promising and more prospective research exploring similar services is required

Towards a Performative Understanding of Deservingness: Merit, Gender and the BBC Pay Dispute

Drawing largely on a high profile case of unequal pay at the BBC (British Broadcasting Corporation) as an illustrative example, this conceptual paper considers differences and interrelationships between merit and deservingness, where the latter captures how, through appropriate performances, merit is given recognition and value. We propose a performative understanding of deservingness that highlights its gendered and embodied dimensions. Informed by Judith Butler’s account of gender performativity, we show that, while merit is conventionally conceptualized as a relatively fixed set of attributes (qualifications, skill) ‘attached’ to the individual, deservingness captures how, in gendered terms, value and recognition are both claimed and conferred. As we argue, a gendered, deserving subject does not pre-exist but is performatively constituted through embodied practices and performances of what is seen as worthy in a particular time and place

Mass Spectrum of a Meson Nonet is Linear

It is argued that the mass spectrum of a meson nonet is linear, consistent with the standard Gell-Mann--Okubo mass formula and leading to an extra Gell-Mann--Okubo mass relation for the masses of the isoscalar states. This relation is shown to hold with an accuracy of up to $\sim$3\% for all well-established nonets. It also suggests a new $q\bar{q}$ assignment for the scalar meson nonet.Comment: 11 pages, LaTeX, 4 postscript figures following the main tex

Electronic anisotropy, magnetic field-temperature phase diagram and their dependence on resistivity in c-axis oriented MgB2 thin films

An important predicted, but so far uncharacterized, property of the new superconductor MgB2 is electronic anisotropy arising from its layered crystal structure. Here we report on three c-axis oriented thin films, showing that the upper critical field anisotropy ratio Hc2par/Hc2perp is 1.8 to 2.0, the ratio increasing with higher resistivity. Measurements of the magnetic field-temperature phase diagram show that flux pinning disappears at H* ~ 0.8Hc2perp(T) in untextured samples. Hc2par(0) is strongly enhanced by alloying to 39 T for the highest resistivity film, more than twice that seen in bulk samples.Comment: 5 pages Acrobat 3.02 pd