Crucial involvement of xanthine oxidase in the intracellular signalling networks associated with human myeloid cell function

Xanthine oxidase (XOD) is an enzyme which plays a central role in purine catabolism by converting hypoxanthine into xanthine and then further into uric acid. Here we report that XOD is activated in THP-1 human myeloid cells in response to pro-inflammatory and growth factor stimulation. This effect occurred following stimulation of THP-1 cells with ligands of plasma membrane associated TLRs 2 and 4, endosomal TLRs 7 and 8 as well as stem cell growth factor (SCF). Hypoxia-inducible factor 1 (HIF-1) and activator protein 1 (AP-1) transcription complexes were found to be responsible for XOD upregulation. Importantly, the mammalian target of rapamycin (mTOR), a major myeloid cell translation regulator, was also found to be essential for XOD activation. Specific inhibition of XOD by allopurinol and sodium tungstate led to an increase in intracellular AMP levels triggering downregulation of mTOR activation by phosphorylation of its T2446 residue. Taken together, our results demonstrate for the first time that XOD is not only activated by pro-inflammatory stimuli or SCF but also plays an important role in maintaining mTOR-dependent translational control during the biological responses of human myeloid cells

Progressive Education: Lesson from the Past and Present

Progressive education is one of the most enduring educational reform movements in this country, with a lifespan of over one hundred years. Although as noted earlier, it waxes and wanes in popularity, many of its practices now appear so regularly in both private and public schools as to have become almost mainstream. But from the schools that were the pioneers, what useful lessons can we learn? The histories of the early progressive schools profiled in Part 1 illustrate what happened to some of the progressive schools founded in the first part of the twentieth century. But even now, they serve as important reminders for educators concerned with the competing issues of stability and change in schools with particular progressive philosophies—reminders, specifically, of the complex nature of school reform

Comparison of a SiO2-CaO-ZnO-SrO Glass Polyalkenoate Cement to Commercial Dental Materials: Glass Structure and Physical Properties

Glass polyalkenoate cements (GPCs) have previously been considered for orthopedic applications. A Zn-GPC (BT 101) was compared to commercial GPCs (Fuji IX and Ketac Molar) which have a setting chemistry analogous to BT 101. Handling properties (working, Tw and setting, Ts times) for BT 101 were shorter than the commercial GPCs. BT 101 also had a higher setting exotherm (Sx - 34 °C) than the commercial GPCs (29 °C). The maximum strengths for BT 101, Fuji IX, and Ketac Molar were 75, 238, and 216 MPa (compressive, σc), and 34, 54, and 62 MPa (biaxial flexural strengths, σf), respectively. The strengths of BT 101 are more suitable for spinal applications than commercial GPCs. © 2012 Springer Science+Business Media New York

Model Independent Properties and Cosmological Implications of the Dilaton and Moduli Sectors of 4-d Strings

We show that if there is a realistic 4-d string, the dilaton and moduli supermultiplets will generically acquire a small mass O(m_{3/2}), providing the only vacuum-independent evidence of low-energy physics in string theory beyond the supersymmetric standard model. The only assumptions behind this result are (i) softly broken supersymmetry at low energies with zero cosmological constant, (ii) these particles interact with gravitational strength and the scalar components have a flat potential in perturbation theory, which are well-known properties of string theories. (iii) They acquire a $vev$ of the order of the Planck scale (as required for the correct value of the gauge coupling constants and the expected compactification scale) after supersymmetry gets broken. We explore the cosmological implications of these particles. Similar to the gravitino, the fermionic states may overclose the Universe if they are stable or destroy nucleosynthesis if they decay unless their masses belong to a certain range or inflation dilutes them. For the scalar states it is known that the problem cannot be entirely solved by inflation, since oscillations around the minimum of the potential can lead to a huge entropy generation at late times. We discus some possible ways to alleviate this entropy problem, that favour low-temperature baryogenesis, and also comment on the possible role of these particles as dark matter candidates or as sources of the baryon asymmetry through their decay.Comment: 15 pages,CERN-TH.6958/93,NEIP-93-006, IEM-FT-75/93, Late

The Irish Cost-Effectiveness Threshold: Does it Support Rational Rationing or Might it Lead to Unintended Harm to Ireland's Health System?

Ireland is one of the few countries worldwide to have an explicit cost-effectiveness threshold. In 2012, an agreement between government and the pharmaceutical industry that provided substantial savings on existing medications set the threshold at €45,000/quality-adjusted life-year (QALY). This replaced a previously unofficial threshold of €20,000/QALY. According to the agreement, drugs within the threshold will be granted reimbursement, whereas those exceeding it may still be approved following further negotiation. A number of drugs far exceeding the threshold have been approved recently. The agreement only applies to pharmaceuticals. There are four reasons for concern regarding Ireland's threshold. The absence of an explicit threshold for non-drug interventions leaves it unclear if there is parity in willingness to pay across all interventions. As the threshold resembles a price floor rather than a ceiling, in principle it only offers a weak barrier to cost-ineffective interventions. It has no empirical basis. Finally, it is probably too high given recent estimates of a threshold for the UK based on the cost effectiveness of services forgone of approximately £13,000/QALY. An excessive threshold risks causing the Irish health system unintended harm. The lack of an empirically informed threshold means the policy recommendations of cost-effectiveness analysis cannot be considered as fully evidence- based rational rationing. Policy makers should consider these issues and recent Irish legislation that defined cost effectiveness in terms of the opportunity cost of services forgone when choosing what threshold to apply once the current industry agreement expires at the end of 2015.Health Research BoardAccess provided by IREL Consortium c/o Maynooth University The Library Maynooth Universit

Practices and perceptions of strength and conditioning in female golf: a survey study of touring professional players

The aim of the study was to provide an understanding of current practices and perceptions of strength and conditioning (S&C) training in female touring professionals. A cross-sectional, explorative survey was undertaken and contained 30 questions separated into four sections: i) general participant information, ii) S&C practices, iii) Likert scale questions on S&C for golf performance, and iv) knowledge and awareness of S&C. A total of 102 players completed the survey with a combination of multiple-choice questions (MCQs), open-ended questions, and Likert Scale style questions utilised throughout. Results showed that ≥ 94% of players believed that strength and power in both the lower and upper body, in addition to flexibility, were the most important physical characteristics to complement golf shot metrics (e.g., clubhead speed [CHS], ball speed, carry distance, etc.). However, 26% of players conducted S&C training only in the off-season, with 21% suggesting that they had a fear of injury from S&C training. When considering the barriers to undertaking S&C training, the most common reasons included time constraints (20%) and players wanting to prioritise golf practice (15%). Finally, 58% of players believed that training in the weight room should replicate the golf swing. Although it is positive to see that the main physical characteristics for golf are well-understood by professional players, it is also evident that further education and knowledge translation is required relating to the application of S&C training for performance enhancement and injury risk mitigation purposes

Experimental Composite Guidance Conduits for Peripheral Nerve Repair: An Evaluation of Ion Release

Poly (lactide-co-glycolide) (PLGA) - Pluronic F127 - glass composites have demonstrated excellent potential, from the perspective of controlled mechanical properties and cytocompatibility, for peripheral nerve regeneration. In addition to controlling the mechanical properties and cytotoxicity for such composite devices, the glass component may mediate specific responses upon implantation via degradation in the physiological environment and release of constituent elements. However, research focused on quantifying the release levels of such therapeutic ions from these experimental medical devices has been limited. To redress the balance, this paper explores the ion release profiles for Si4+, Ca2+, Na+, Zn 2+, and Ce4+ from experimental composite nerve guidance conduits (CNGC) comprising PLGA (at 12.5, and 20 wt.%), F127 (at 0, 2.5 and 5 wt.%) and various loadings of Si-Ca-Na-Zn-Ce glass (at 20 and 40 wt.%) for incubation periods of up to 28 days. The concentration of each ion, at various time points, was determined using Inductively Coupled Plasma-Atomic Emission Spectrometry (Perkin Elmer Optima 3000). It was observed that the Si4+, Na+, Ca2+, Zn2+ release from CNGCs in this study ranged from 0.22 to 6.477 ppm, 2.307 to 3.277 ppm, 40 to 119 ppm, and 45 to 51 ppm, respectively. The Ce 4+ concentrations were under the minimum detection limits for the ICP instrument utilized. The results indicate that the ion release levels may be appropriate to mediate therapeutic effects with respect to peripheral nerve regeneration. The data generated in this paper provides requisite evidence to optimize composition for pre-clinical evaluation of the experimental composite. © 2012 Elsevier B.V

Monitoring the CMS strip tracker readout system

The CMS Silicon Strip Tracker at the LHC comprises a sensitive area of approximately 200 m2 and 10 million readout channels. Its data acquisition system is based around a custom analogue front-end chip. Both the control and the readout of the front-end electronics are performed by off-detector VME boards in the counting room, which digitise the raw event data and perform zero-suppression and formatting. The data acquisition system uses the CMS online software framework to configure, control and monitor the hardware components and steer the data acquisition. The first data analysis is performed online within the official CMS reconstruction framework, which provides many services, such as distributed analysis, access to geometry and conditions data, and a Data Quality Monitoring tool based on the online physics reconstruction. The data acquisition monitoring of the Strip Tracker uses both the data acquisition and the reconstruction software frameworks in order to provide real-time feedback to shifters on the operational state of the detector, archiving for later analysis and possibly trigger automatic recovery actions in case of errors. Here we review the proposed architecture of the monitoring system and we describe its software components, which are already in place, the various monitoring streams available, and our experiences of operating and monitoring a large-scale system

Selection and phylogenetics of salmonid MHC class I: wild brown trout (Salmo trutta) differ from a non-native introduced strain

We tested how variation at a gene of adaptive importance, MHC class I (UBA), in a wild, endemic Salmo trutta population compared to that in both a previously studied non-native S. trutta population and a co-habiting Salmo salar population ( a sister species). High allelic diversity is observed and allelic divergence is much higher than that noted previously for cohabiting S. salar. Recombination was found to be important to population-level divergence. The alpha 1 and alpha 2 domains of UBA demonstrate ancient lineages but novel lineages are also identified at both domains in this work. We also find examples of recombination between UBA and the non-classical locus, ULA. Evidence for strong diversifying selection was found at a discrete suite of S. trutta UBA amino acid sites. The pattern was found to contrast with that found in re-analysed UBA data from an artificially stocked S. trutta population

Characterisation of Ga2O3-Na2O-CaO-ZnO- SiO2 Bioactive Glasses

The structural role of Gallium (Ga) is investigated when substituted for Zinc (Zn) in a 0.42SiO2-0.40-xZnO-0.10Na2O-0.08CaO glass series, (where x = 0.08). Each starting material was amorphous, and the network connectivity (NC) was calculated assuming Ga acts as both a network modifier (1.23), and also as a network former. Assuming a network forming role for Ga the NC increased with increasing Ga concentration throughout the glass series (Control 1.23, TGa-1 2.32 and TGa-2 3.00). X-ray photoelectron spectroscopy confirmed both composition and correlated NC predictions. Raman spectroscopy was employed to investigate Q-structure and found that a shift in wavenumbers occurred as the Ga concentration increased through the glass series, from 933, 951 to 960 cm-1. Magic angle spinning nuclear magnetic resonance determined a chemical shift from -73, -75 to -77 ppm as the Ga concentration increased, supporting Raman data. These results suggest that Ga acts predominantly as a network former in this particular Zn-silicate system. © 2013 Springer Science+Business Media New York