Naresuan University Journal
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Statins inhibit insulin-like growth factor action in first trimester placenta by altering insulin-like growth factor 1 receptor glycosylation
No full textThe rapid rise in obesity, metabolic syndrome and type 2 diabetes is one of the major healthcare problems of the Western world. Affected individuals are often treated with statins (3-hydroxy-3-methylglutaryl co-enzyme A [HMG CoA] reductase inhibitors) to reduce circulating cholesterol levels and the risk of developing cardiovascular disease; given the evolving demographic profile of these conditions, such drugs are increasingly prescribed to women of reproductive age. We have previously shown that exposure of placental tissue to statins inhibits the action of insulin-like growth factors (IGF)-I and -II which are key regulators of trophoblast proliferation and placental development. N-linked glycans in the IGF receptor, IGF1R, influence its presentation at the cell surface. This study aimed to determine whether statins, which are known to affect N-glycosylation, modulate IGF1R function in placenta. Treatment of first trimester villous tissue explants with statins (pravastatin or cerivastatin) or inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin or castanospermine) altered receptor distribution in trophoblast and attenuated proliferation induced by IGF-I or IGF-II (Ki67; P <0.05, n = 5). Decreased binding of Phaseolus vulgaris lectin and phytohaemagglutinin to IGF1R immunoprecipitated from treated explants demonstrated reduced levels of complex N-linked glycans. Co-incubation of tissue explants with statins and farnesyl pyrophosphate (which increases the supply of dolichol intermediates), prevented statin-mediated disruption of IGF1R localization and reversed the negative effect on IGF-mediated trophoblast proliferation. These data suggest that statins attenuate IGF actions in the placenta by inhibiting N-linked glycosylation and subsequent expression of mature IGF1R at the placental cell surface
Biogenic nano-magnetite and nano-zero valent iron treatment of alkaline Cr(VI) leachate and chromite ore processing residue
No full textHighly reactive nano-scale biogenic magnetite (BnM), synthesized by the Fe(III)-reducing bacterium Geobacter sulfurreducens, was tested for the potential to remediate alkaline Cr(VI) contaminated waters associated with chromite ore processing residue (COPR). The performance of this biomaterial, targeting aqueous Cr(VI) removal, was compared to a synthetic alternative, nano-scale zero valent iron (nZVI). Samples of highly contaminated alkaline groundwater and COPR solid waste were obtained from a contaminated site in Glasgow, UK. During batch reactivity tests, Cr(VI) removal from groundwater was inhibited by ∼25% (BnM) and ∼50% (nZVI) when compared to the treatment of less chemically complex model pH 12 Cr(VI) solutions. In both the model Cr(VI) solutions and contaminated groundwater experiments the surface of the nanoparticles became passivated, preventing complete coupling of their available electrons to Cr(VI) reduction. To investigate this process, the surfaces of the reacted samples were analyzed by TEM-EDX, XAS and XPS, confirming Cr(VI) reduction to the less soluble Cr(III) on the nanoparticle surface. In groundwater reacted samples the presence of Ca, Si and S was also noted on the surface of the nanoparticles, and is likely responsible for earlier onset of passivation. Treatment of the solid COPR material in contact with water, by addition of increasing weight % of the nanoparticles, resulted in a decrease in aqueous Cr(VI) concentrations to below detection limits, via the addition of ⩾5% w/w BnM or ⩾1% w/w nZVI. XANES analysis of the Cr K edge, showed that the % Cr(VI) in the COPR dropped from 26% to a minimum of 4–7% by the addition of 5% w/w BnM or 2% w/w nZVI, with higher additions unable to reduce the remaining Cr(VI). The treated materials exhibited minimal re-mobilization of soluble Cr(VI) by re-equilibration with atmospheric oxygen, with the bulk of the Cr remaining in the solid fraction. Both nanoparticles exhibited a considerable capacity for the remediation of COPR related Cr(VI) contamination, with the synthetic nZVI demonstrating greater reactivity than the BnM. However, the biosynthesized BnM was also capable of significant Cr(VI) reduction and demonstrated a greater efficiency for the coupling of its electrons towards Cr(VI) reduction than the nZVI
Breast Cancer Resistance Protein (ABCG2) in Clinical Pharmacokinetics and Drug Interactions: Practical Recommendations for Clinical Victim and Perpetrator Drug-Drug Interaction Study Design
No full textCriminal Law and Religion in England and Wales
No full textEl Derecho Penal de Inglaterra y Gales es un ejemplo paradigmatico de la forma en que el sistema legal britanico se ocupa de la religion. Es incuestionable que en la actualidad Inglaterra y Gales son mas diversas, tanto cultural como ideologicamente, de lo que fueron en previas generaciones, de la misma manera que la fe anglicana no disfruta de una posicion de dominio, tal y como sucedio en el pasado. Sin embargo, esto no ha llevado a una disminucion del valor de la religion en el ambito legal britanico, ni a la defensa de valores seculares, potencialmente universales en detrimento de los espirituales
Overweight and obesity may lead to under-diagnosis of airflow limitation: findings from the Copenhagen City Heart Study.
No full textBACKGROUND: The prevalence of obesity has increased during the last decades and varies from 10-20% in most European countries to approximately 32% in the United States. However, data on how obesity affects the presence of airflow limitation (AFL) defined as a reduced ratio between forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) are scarce. METHODS: Data was derived from the third examination of the Copenhagen City Heart Study from 1991 until 1994 (n = 10,135). We examine the impact of different adiposity markers (weight, body mass index (BMI), waist circumference, waist-hip ratio, and abdominal height) on AFL. AFL was defined in four ways: FEV1/FVC ratio <0.70, FEV1/FVC ratio <lower limit of normal (LLN), FEV1/FVC rati
A LOFAR census of non-recycled pulsars: average profiles, dispersion measures, flux densities, and spectra:average profiles, dispersion measures, flux densities, and spectra
No full textWe present first results from a LOFAR census of non-recycled pulsars. The census includes almost all such pulsars known (194 sources) at declinations {\rm Dec}> 8^\circ and Galactic latitudes |{\rm Gb}| > 3^\circ, regardless of their expected flux densities and scattering times. Each pulsar was observed for minutes in the contiguous frequency range of 110--188 MHz. Full-Stokes data were recorded. We present the dispersion measures, flux densities, and calibrated total intensity profiles for the 158 pulsars detected in the sample. The median uncertainty in census dispersion measures ( pc cm) is ten times smaller, on average, than in the ATNF pulsar catalogue. We combined census flux densities with those in the literature and fitted the resulting broadband spectra with single or broken power-law functions. For 48 census pulsars such fits are being published for the first time. Typically, the choice between single and broken power-laws, as well as the location of the spectral break, were highly influenced by the spectral coverage of the available flux density measurements. In particular, the inclusion of measurements below 100 MHz appears essential for investigating the low-frequency turnover in the spectra for most of the census pulsars. For several pulsars, we compared the spectral indices from different works and found the typical spread of values to be within 0.5--1.5, suggesting a prevailing underestimation of spectral index errors in the literature. The census observations yielded some unexpected individual source results, as we describe in the paper. Lastly, we will provide this unique sample of wide-band, low-frequency pulse profiles via the European Pulsar Network Database
Group Aggregation of Pairwise Comparisons using Multi-Objective Optimization
No full textIn group decision making, multiple decision makers (DMs) aim to reach a consensus ranking of alternatives in a decision problem. The differing expertise, experience and, potentially conflicting, interests of the DMs will result in the need for some form of conciliation to achieve consensus. Pairwise comparisons are commonly used to elicit values of preference of a DM. The aggregation of the preferences of multiple DMs must additionally consider potential conflict between DMs and how these conflicts may result in a need for compromise to reach group consensus. We present an approach to aggregating the preferences of multiple DMs, utilizing multi-objective optimization, to derive and highlight underlying conflict between the DMs when seeking to achieve consensus. Extracting knowledge of conflict facilitates both traceability and transparency of the trade-offs involved when reaching a group consensus. Further, the approach incorporates inconsistency reduction during the aggregation process to seek to diminish adverse effects upon decision outcomes. The approach can determine a single final solution based on either global compromise information or through utilizing weights of importance of the DMs. Within multi-criteria decision making, we present a case study within the Analytical Hierarchy Process from which we derive a richer final ranking of the decision alternatives
Access and non-access site bleeding after percutaneous coronary intervention and risk of subsequent mortality and major adverse cardiovascular events: systematic review and meta-analysis.
No full textBACKGROUND: The prognostic impact of site-specific major bleeding complications after percutaneous coronary intervention (PCI) has yielded conflicting data. The aim of this study is to provide an overview of site-specific major bleeding events in contemporary PCI and study their impact on mortality and major adverse cardiovascular event outcomes. METHODS AND RESULTS: We conducted a meta-analysis of PCI studies that evaluated site-specific periprocedural bleeding complications and their impact on major adverse cardiovascular events and mortality outcomes. A systematic search of MEDLINE and Embase was conducted to identify relevant studies and random effects meta-analysis was used to estimate the risk of adverse outcomes with site-specific bleeding complications. Twenty-five relevant studies including 2,400,645 patients that underwent PCI were identified. Both non-access site (risk ratio [RR], 4.06; 95% confidence interval [CI], 3.21-5.14) and access site (RR, 1.71; 95% CI, 1.37-2.13) related bleeding complications were independently associated with an increased risk of periprocedural mortality. The prognostic impact of non-access site-related bleeding events on mortality related to the source of anatomic bleeding, for example, gastrointestinal RR, 2.78; 95% CI, 1.25 to 6.18; retroperitoneal RR, 5.87; 95% CI, 1.63 to 21.12; and intracranial RR, 22.71; 95% CI, 12.53 to 41.15. CONCLUSIONS: The prognostic impact of bleeding complications after PCI varies according to anatomic source and severity. Non-access site-related bleeding complications have a similar prevalence to those from the access site but are associated with a significantly worse prognosis partly related to the severity of the bleed. Clinicians should minimize the risk of major bleeding complications during PCI through judicious use of bleeding avoidance strategies irrespective of the access site used
A Photoelectron Spectroscopy Study of Stoichiometric and Reduced Anatase TiO2 (101) Surfaces: The Effect of Subsurface Defects on Water Adsorption at Near-Ambient Pressures
No full textX-ray photoelectron (XPS) experiments at normal and grazing emission are performed, demonstrating the labile nature of the anatase TiO2(101) surface after argon cluster ion sputtering and the propensity of oxygen vacancies to migrate subsurface at room temperature. Near-ambient XPS (NAP-XPS) shows that molecular water adsorbs on the anatase TiO2(101) surface at pressures of 0.6 mbar and above, at room temperature, in a mixed molecular and dissociated state. Water adsorbs in a similar fashion on both sputtered and stoichiometric surfaces and reaches a saturation point between 0.6 and 1.8 mbar at room temperature. This means there is little difference in reactivity with regards to water adsorption on both sputtered and stoichiometric surfaces, giving credence to the theory that anatase has superior photocatalytic activity over rutile due to the tendency of oxygen vacancies to lie subsurface, therefore being able to contribute to photocatalysis without being quenched by adsorbates