509 research outputs found

    Non-covalent dimerisation of a bicyclic aromatic oligomer via loop–loop interlocking in the solid state

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    A macrobicyclic ether-ketone oligomer containing twenty aromatic rings has been isolated from the products of nucleophilic condensation between 4,40-(9-fluorenylidene)diphenol and 1,3,5- tris(40-fluorobenzoyl)benzene. Reduction of all six carbonyl groups to methylene units yields a derivative which exhibits non-covalent dimerisation in the crystalline state via shape-complementary interlocking of fluorenylidene-containing ‘‘ loop ’’ regions

    Openings of the rat recombinant alpha1 homomeric glycine receptor as a function of the number of sgonist molecules bound

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    The functional properties of rat homomeric {alpha}1 glycine receptors were investigated using whole-cell and outside-out recording from human embryonic kidney cells transfected with rat {alpha}1 subunit cDNA. Whole-cell dose-response curves gave EC50 estimates between 30 and 120 µM and a Hill slope of ~3.3. Single channel recordings were obtained by steady-state application of glycine (0.3, 1, or 10 µM) to outside-out patches. Single channel conductances were mostly 60–90 pS, but smaller conductances of ~40 pS were also seen (10% of the events) with a relative frequency that did not depend on agonist concentration. The time constants of the apparent open time distributions did not vary with agonist concentration, but short events were more frequent at low glycine concentrations. There was also evidence of a previously missed short-lived open state that was more common at lower glycine concentrations. The time constants for the different components of the burst length distributions were found to have similar values at different concentrations. Nevertheless, the mean burst length increased with increasing glycine. This was because the relative area of each burst-length component was concentration dependent and short bursts were favored at lower glycine concentrations. Durations of adjacent open and shut times were found to be strongly (negatively) correlated. Additionally, long bursts were made up of longer than average openings separated by short gaps, whereas short bursts usually consisted of single isolated short openings. The most plausible explanation for these findings is that long bursts are generated when a higher proportion of the five potential agonist binding sites on the receptor is occupied by glycine. On the basis of the concentration dependence and the intraburst structure we provide a preliminary kinetic scheme for the activation of the homomeric glycine receptor, in which any number of glycine molecules from one to five can open the channel, although not with equal efficiency

    Pressure groups and government policy on education, 1800 - 1839.

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    This study examines the roles of the principal groups and individuals, who, during the years 1800-1839, promoted the education of the poor and pressurised governments with the notion that the state ought to ac ept responsibility for the formation of a nationa1 system. Their m tives were primarily religious, philanthropic or political with a degree of self-interest in the desire to preserve order in society. The religious interests are examined mainly through the work of the British and Foreign Sch ol Society, which served the Dissenter traditi ns, and the Nati nal S ciety which defended the prerogative of the Establi h d Church t superintend the education of the people. The tilitarians and Radicals were imp rtant for the practica1 expression f their philos phical and political ideas led them to make a considerable c ntributi n to the provision schools. They also had the inspiration and organising ability of Jam s Mill and Francis Place. The ideas of Robert Owen are considered because he was a pressure figure for a few years, but his work also sowed the seeds of Co-operation and w rking-cla s movements, which made an impact during the 1830's. As the populati n slowly improved in standard of learning, the development of Mechanics' Institutes, the Society for the Difflision of Useful Knowledge and the foundation of University College are viewed as part of a strategy for the general promotion of adult education1 The dominant personality of Henry Brougham is evident in much of this study. He instituted the Charity Commissions in 1819, was spokesman (iv) for education in Parliament for many years, anj was a link between the different groups because of his involvement in so many. During the 1830's the new science of statistics emerged and the Statistical Societies were important for their presentation of data on education1 The existence of a National Board of Education in Ireland after 1831 placed the province ahead of England and the influences from this experiment, mediated to Parliament by Thomas Wyse and others, all helped to pressurise the governments of the day, whose policy had been to encourage voluntary effort and to avoid the imposition of central administrative control

    How to Impose Microscopic Reversibility in Complex Reaction Mechanisms

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    Most, but not all, ion channels appear to obey the law of microscopic reversibility (or detailed balance). During the fitting of reaction mechanisms it is therefore often required that cycles in the mechanism should obey microscopic reversibility at all times. In complex reaction mechanisms, especially those that contain cubic arrangements of states, it may not be obvious how to achieve this. Three general methods for imposing microscopic reversibility are described. The first method works by setting the ‘obvious’ four-state cycles in the correct order. The second method, based on the idea of a spanning tree, works by finding independent cycles (which will often have more than four states) such that the order in which they are set does not matter. The third method uses linear algebra to solve for constrained rates

    Studies of NMDA receptor function and stoichiometry with truncated and tandem subunits

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    The subunits that compose eukaryotic glutamate ion channel receptors have three transmembrane domains (TMs) and terminate with intracellular tails that are important for controlling channel expression and localization. Truncation of NMDA receptor subunits before the final TM showed that this TM and intracellular tail region are necessary to form functional channels. However, it is shown here that these truncated subunits may be partially rescued by coexpressing the final TM and tail as a separate protein. The whole-cell currents so produced are somewhat lower than with full-length subunits, and they do not show the sag characteristic of currents from channels containing NR1 and NR2A subunits in the continued presence of an agonist. In addition, these truncated subunits were joined to full-length subunits to generate tandems. The functional expression of these tandems confirmed the tetrameric structure of NMDA receptors and also suggested that the subunits making up NMDA receptors are arranged as a dimer of dimers in the receptors with a 1-1-2-2 orientation of the subunits in the channel, and not in an alternating pattern of subunits around the pore. These results may redirect future studies into the mechanism of binding and gating in these receptors toward schemes including dimers, and may also be relevant to studies of glutamate receptor ion channels in general

    Group of students, National Gallery Art School, Melbourne 1887 [picture].

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    Assumed to be the original of the ill. in: The story of Australian art / by William Moore.; P329. Names listed on reverse: J. Llewellyn Jones, Alexander Colquhoun, E. Phillips Fox, Frederick McCubbin, John Longstaff, Tudor St. George Tucker, J. J. Gibbs, A. Altson, David Davies, Fred M. Williams

    Jüri Okas’ ‘specific objects’: diverging discourses in Estonian Art in the 1970s.

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    Previously in the University eprints HAIRST pilot service at http://eprints.st-andrews.ac.uk/archive/00000367/Article 3 of 6 in issue devoted to the visual culture of the Scandinavian and Baltic region.This article will look at the early works of Estonian architect and artist Jüri Okas and will try to work between diverging languages and interpretations, reading works by Okas against the background of Anglo-american conceptualism and minimalism of the same period. The first part of the paper will analyse a print by Jüri Okas that paraphrases works by the American artist Donald Judd and will try to show how Okas’ concept of minimalism differed from the Western one and the reasons behind it. The second part of the paper will focus on a conceptual book by Jüri Okas, consisting of a series of photographs of everyday and banal architectural objects, and compare it to Rober Venturi’s book on Complexity and Contradiction in Architecture. Finally, a comparison will be made with works of Robert Smithson in the context of concepts of waste, excess and the remainders of industrial civilisationPostprin

    16S sequencing and functional analysis of the fecal microbiome during treatment of newly diagnosed pediatric inflammatory bowel disease

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    JJA is funded by a National Institute of Health Research Academic Clinical Fellowship and has received an Action Medical Research training fellowship. TC is funded by a Crohn’s in Childhood research association fellowship. CMC received a PhD studentship from SULSA Spirit industrial studentship. The NGS analysis was made possible by the award of a grant from the Source Bioscience 110th year anniversary promotion to CMC. The Rowett Institute receives funding from the Scottish Government (RESAS).Peer reviewe

    Dietary intervention to lower serum cholesterol

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    Background: Dietary intervention to lower serum LDL- cholesterol (LDL-C) is effective, yet underutilised in general practice. Objective: This report summarises the findings of an expert roundtable convened to review the evidence relating to dietary interventions to lower serum LDL-C. Discussion: Interventions that lower LDL-C lower the risk of cardiovascular disease. Comprehensive dietary intervention is indicated in all patients with an absolute 5 year risk for coronary disease of 10% or greater. Short term trials indicate that these interventions have the potential to lower LDL-C by approximately 20%. A year long trial has shown mean LDL-C lowering of 13%, with about one-third of subjects achieving a reduction greater than 20%, highlighting the importance of adherence to dietary advice. The most effective dietary strategies are replacing saturated and trans fatty acids with poly- and monounsaturated fats and increasing intake of plant sterols. Losing weight and increasing soluble fibre and soy protein intake can also lower serum cholesterol and may be considered when recommending a nutritionally balanced, cholesterol lowering diet. Motivational interviewing by general practitioners can improve the effectiveness of brief, behaviour orientated advice and dietary counselling to lower serum cholesterol.Peter Clifton, David Colquhoun, Claire Hewat, Peter Jones, John Litt, Manny Noakes, Richard O'Brien, Bill Shrapnel, Murray Skeaffhttp://www.racgp.org.au/scriptcontent/search/afpsearchresults.cfm?cx=000337812831128799297%3Acwnpztvg-0a§ion=Australian_Family_Phys&cof=FORID%3A11&searchterm=Dietary+intervention+to+lower+serum+cholesterol&x=67&y=1

    Lipid-modifying therapy in the elderly

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    Ian Hamilton-Craig,1,2 David Colquhoun,3,4 Karam Kostner,4,5 Stan Woodhouse,4,6 Michael d'Emden4,7 1Griffith University School of Medicine, Griffith Health Institute, Gold Coast, QLD, Australia; 2Flinders University School of Medicine, Adelaide, SA, Australia, 3Wesley Medical Centre, Auchenflower, QLD, Australia; 4University of Queensland, Brisbane, QLD, Australia; 5Department of Cardiology, Mater Hospital, Woolloongabba, QLD, Australia; 6Taylor Medical Centre, Woolloongabba, QLD, Australia; 7Department of Endocrinology, Royal Brisbane Hospital, Herston, QLD, AustraliaAbstract: Cardiovascular disease (CVD) mortality and morbidity increases with increasing age, largely as a result of increased lifetime exposure as well as increased prevalence of CVD risk factors. Hospitalization for CVD increases by a factor of over 18× for those aged 85+ years versus those aged <30 years. In spite of this, life expectancy continues to increase, and in Australia for people reaching the age of 65 years, it is now 84 years in men and 87 years in women. The number of people for whom lipid management is potentially indicated therefore increases with aging. This is especially the case for secondary prevention and for people aged 65–75 years for whom there is also evidence of benefit from primary prevention. Many people in this age group are not treated with lipid-lowering drugs, however. Even those with CVD may be suboptimally treated, with one study showing treatment rates to fall from ~60% in those aged <50 years to <15% for those aged 85+ years. Treatment of the most elderly patient groups remains controversial partly from the lack of randomized trial intervention data and partly from the potential for adverse effects of lipid therapy. There are many complex issues involved in the decision to introduce effective lipid-lowering therapy and, unfortunately, in many instances there is not adequate data to make evidence-based decisions regarding management. This review summarizes the current state of knowledge of the management of lipid disorders in the elderly and proposes guidelines for management.Keywords: lipid management, elderly, statin
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