Methylation of DNA plays an important role in the control of gene expression in higher eukaryotes. This is largely achieved by the packaging of methylated DNA into chromatin structures that are inaccessible to transcription factors and other proteins. Methylation involves the addition of a methyl group to the 5‐position of the cytosine base in DNA, a reaction catalysed by a DNA (cytosine‐5) methyltransferase. This reaction occurs in nuclear replication foci where the chromatin structure is loosened for replication, thereby allowing access (...) to methyltransferases. Partly as a result of their recognising the presence of a methylcytosine on the parental strand following replication, these large enzymes are able to maintain the distribution of methyl groups along the DNA of somatic cells and, thereby, maintain tissue‐specific patterns of gene expression. (shrink)

This article critically evaluates the Medicines and Healthcare products Regulatory Agency’s announcement, in March 2008, that GlaxoSmithKline would not face prosecution for deliberately withholding trial data, which revealed not only that Seroxat was ineffective at treating childhood depression but also that it increased the risk of suicidal behaviour in this patient group. The decision not to prosecute followed a four and a half year investigation and was taken on the grounds that the law at the relevant time was insufficiently clear. (...) This article assesses the existence of significant gaps in the duty of candour which had been assumed to exist between drugs companies and the regulator, and reflects upon what this episode tells us about the robustness, or otherwise, of the UK’s regulation of medicines. (shrink)

Several essays, articles, and papers have appeared during the last fifteen years which have shed light on the place and function of science in the intellectual life of eighteenth-century Scotland. Some have concentrated on ideological factors such as the increasing concerns with polite culture, improvement, and the reaction of the Scottish élite to the Act of Union. Others have noted the roles of Jacobites and Whigs in the production of a culture which was unique to Scotland. The generalist educational ideals (...) held by Scots have been explored, as have their philosophical, methodological, and mathematical traditions. Another set of papers has fruitfully examined ‘the social role of knowledge’ and has attempted through studies of the politics of Scottish science and a consideration of its audience to show how the characteristics of local provincial society could influence if not ‘determine scientific activity, its social organization or intellectual structure’. Concerns with the institutionalization of scientific activities and the acceptance of new values have also led to studies of the universities, medical corporations, and societies which provided focuses for scientific enquiry. All of these studies have emphasized the aspects of science north of the Tweed between about 1690 and 1830 which seem uniquely Scottish. No one would deny the value of these works but perhaps it is now time to redress the balance and to notice how typical much of the scientific work of the Scots was, and how easily it and the institutions through which it was pursued can be fitted into the wider context of the European Enlightenment. (shrink)

The Philosophical Society of Edinburgh which had flourished for a few years after 1738 was as good as dead in 1748. Lord Morton, its President, now lived most of the time in London whence he wrote to Sir John Clerk in 1747 that he regarded the Society as ‘annihilated’, apparently thinking that the death of Colin MacLaurin in 1746 and the temporary retirement to the countryside of its other Secretary, Andrew Plummer, had put an end to it. Sir John had (...) hoped to revive it through association with the Royal Society of London, but Morton did not encourage him in this scheme, about which he had ‘great doubts’. The Society needed a mathematician and an experimenter who could carry on the consulting work which MacLaurin had done, but Morton glumly wondered if ‘the new professor of Mathematics [Matthew Stewart] will be as zealous as MacLaurin had been.’ The Society's other officers, Dr John Clerk and Alexander Lind, are not known to have tried to revive the Society. Perhaps they were discouraged by the fact that ten of the members of the Society were dead, and that six more had left the kingdom. At least three others were likely to have been habitually absent from meetings because they lived some distance from Edinburgh. Of the remaining forty-five known members in 1748, nine were over sixty-one years of age with four being between seventy-one and seventy-six. In 1737 the average age of thirty-eight of the founders had been 46.0, but by 1748 it had risen to 53.9 for the thirty-three men for whom it can be calculated. Disruption, death, and age had diminished enthusiasm for the Society and jeopardized its survival. Only two meetings are known to have been held in 1746. Sir John's letter to Morton about affiliation with the Royal Society is the only clear sign of life in 1747. We may well ask why this floundering body survived, to whom and to what it owed its revival? The answers to these questions tell us something about the intellectual needs and interests of the Edinburgh intelligentsia of the mid-eighteenth century. (shrink)

This paper shows that in late seventeenth-century Scotland there existed a sizeable virtuoso community whose leaders were abreast of European developments in philosophy, history and science. Moreover, by c. 1700, Sir Robert Sibbald was attempting to organize a learned society modelled upon those he knew in Europe and upon London's Royal Society. The interests of the virtuosi and their attempts to institutionalize their pursuits laid much of the ground work for the Scottish Enlightenment. The Royal Society of Scotland which Sir (...) Robert hoped to found never became a reality, but the academic ideals which he propounded came to fruition in the Philosophical Society of Edinburgh and later bodies such as the Royal Society of Edinburgh and the Society of Antiquaries of Scotland. The intellectual inquiries and achievements of Sir Robert and his friends, particularly those in medicine and natural history, continued to be of interest to later Scots. They, thanks in part to the influence of the Newtonian physician Archibald Pitcaire, improved upon Sibbald's naïve Baconianism, but to a surprising degree their concerns had also been his. (shrink)

The story of the end of the Philosophical Society of Edinburgh in 1783, is linked with that of the founding of the Society of Antiquaries of Scotland and the Royal Society of Edinburgh , both of which were given Royal Charters sealed on 6 May 1783. It is a story which has been admirably told by Steven Shapin. He persuasively argued that the P.S.E. was a casualty of bitter quarrels rooted in local Edinburgh politics, in personal animosities and in disputes (...) about the control of cultural property and intellectual leadership. In all this he was surely correct just as he was in finding the principal actors in this controversy to be: David Erskine, 11th Earl of Buchan; the Reverend Dr John Walker, Professor of Natural History in Edinburgh University; Dr William Cullen, Professor of the Theory and Practice of Medicine and Vice-President of the P.S.E.; Mr William Smellie, Printer to the Society of Antiquaries; Henry Home, Lord Kames, S.C.J. and President of the P.S.E.; Sir George Clerk-Maxwell, Vice-President of the P.S.E.; John Robison, Professor of Natural Philosophy and Secretary to the P.S.E.; Edinburgh University's Principal, William Robertson; the Curators of the Advocates Library: Ilay Campbell, Robert Blair, Alexander Abercromby, Alexander Fraser Tytler, Professor of Public Law; Henry Dundas, Lord Advocate and M.P. for Midlothian. In a peripheral way, the Royal Colleges of Physicians and Surgeons were probably also involved; so too were Lord Buchan's brothers, Henry and Thomas Erskine, Foxite Whigs who opposed Dundas politically. Henry Erskine displaced Dundas as Lord Advocate in August 1783. After the change of ministry on 18 December 1783 he was ousted, but became Dean of the Faculty of Advocates in 1785. National as well as burgh politics touched these disputes and gave the parties of the Erskines and Dundas and his friends some leverage in London. (shrink)

The Philosophical Society of Edinburgh Throughout the years 1768–1783 looked to the outside world like a flourishing and important body. By 1771 it had sponsored the publication of five volumes of papers which had gone through several printings and translations. It had a distinguished foreign membership which assured its recognition abroad as one of the important academic bodies in the cosmopolitan Republic of Letters. From its foundation in 1737 until his death in 1768, its President had been the Earl of (...) Morton, better known as the President of the Royal Society of London and as an astronomer who had been active in the practical work of the London society. Another member, Sir John Pringle, became President of the Royal Society in 1772. It was also known abroad that among the Edinburgh philosophers were to be found the most important professors of the town's university, not only those of its distinguished medical faculty but also men like William Robertson, Adam Ferguson and later John Robison. David Hume had been at one time a Secretary of the Society and probably remained a member to the end of his life in 1776. In the British colonies, the Society could point to members in Pennsylvania, South Carolina, Jamaica and other West Indian islands and it had contacts in a far-flung network reaching from China and Siberia in the east to places less remote in Europe and America. Within Britain, the Society had members in London and in provincial towns of whom William Brownrigg was the most important. From these men and from others scattered in Scotland, the Society drew information and projected its image as a successful learned society. These appearances, however, are far clearer than the Society's record of accomplishment during its last years. It is not accidental that so little pertaining to its work survives. The Society in reality had a career far from brilliant and by 1778 hardly deserved the reputation it had acquired. During its last five years it revived but even then it probably did not reach the level of activity seen in the early and mid 1750s. (shrink)

L'analyse d'une cinétique de croissance y est conduite à partir du modèle logistique généralisé de Richards-Nelder. On distingue 2 types de processus dits mono- et multi-logistique. Dans le cas mono-logistique, le phénomène est correctement décrit par une seule fonction logistique. La cinétique de croissance est alors caractérisée par lea propriétés de chacune des phases G 1 à G 4, délimitées par les points singuliers Γmax, V max et Γmin. On appelle structure de croissance la contribution relative de ces différentes phases (...) à l'expression de la croissance totale. Cette distribution temporelle de l'activité de croissance est une représentation discrétisée de la trajectoire y 0 → y max. On appelle processus multi-logistique toute cinétique de croissance correspondant à une somme de 2 ou plusieurs logistiques généralisées. II existe alors un plus grand nombre de points singuliers et donc un plus grand nombre de phases G i que dans le cas monologistique. La structure de croissance définit avec précision la cinetique du phénomène, ainsi que l'importance relative des différentes composantes logistiques au cours du temps. Une application en est donnée avec le grandissement des cellules pleuridiophores de l'Algue Antithamnion plumula. L'allongement de ces cellules est toujours de type bi-logistique. Les caractéristiques de la structure de croissance permettent une discrimination nette du sporophyte et des gametophytes mâle et femelle. Tandis que la composante 1 est pen différente, la composante 2 varie fortement selon la ploïdie du thalle. En revanche, il y a pen de différences entre les deux gamétophytes. Cette notion de structure de croissance est ainsi susceptible d'apporter des résultats originaux. Audelà de cet example, cette approche est proposée comme une méthode de caractérisation simple mais précise de toute cinétique de croissance basée sur lea variations temporelles de l'activité de croissance [couple ]. (shrink)

It is in the Corinthian letters that the all-important evidence for a Christian interpretation of King Lear lies; for the major theme is love.

Amateur scientists were important in the science of the eighteenth century as patrons, investors in talent and new equipment, as the maintainers of gardens and libraries, and, occasionally, as men who could and did make discoveries or significant innovations. The article shows that the 3rd Duke of Argyll was one of these men. He was also much more. Ilay's interests in science, because of his important political position in Scotland, touched not only his immediate friends but helped to reshape Scottish (...) culture itself. This essay looks at his scientific interests, his political career, and his patronage to argue that the results of his long career in politics were to institutionalize a new set of modern values in most Scottish institutions. (shrink)

The world in which the Scottish Enlightenment took shape -- Archibald Campbell, 3rd Duke of Argyll (1682-1761) : patronage and the creation of the Scottish Enlightenment -- How many Scots were enlightened? -- What did eighteenth-century Scottish students read? -- Our excellent and never to be forgotten friend : David Hume (26 April 1711- 25 August 1776) -- Hume's intellectual development : part II, 1711-1762 -- Hume's histories -- Hume's economics -- Numbering the medics -- Numbers and money -- Who (...) were they? -- The émigrés as they appear in the American sample. (shrink)

Prior research indicates that managers’ dark personality traits increase their tendency to engage in disruptive and unethical organizational behaviors including accounting earnings management. Other research suggests that the prevalence of dark personalities in management may represent an accidental byproduct of selecting managers with accompanying desirable attributes that fit the stereotype of a “strong leader.” Our paper posits that organizations may hire some managers who have dark personality traits because their willingness to push ethical boundaries aligns with organizational objectives, particularly in (...) the accounting context where ethical considerations are especially important. Using several validation studies and experiments, we find that experienced executives and recruiting professionals favor hiring a candidate with dark personality traits into an accounting management position over an otherwise better-qualified candidate when the hiring organization faces pressure to manage earnings. Our results help to illuminate why individuals with dark personality traits may effectively compete for high-level accounting positions. (shrink)

Roger L. Taylor; V—Sexual Experiences, Proceedings of the Aristotelian Society, Volume 68, Issue 1, 1 June 1968, Pages 87–104, https://doi.org/10.1093/aristotel.

Roger L. Taylor; V—Sexual Experiences, Proceedings of the Aristotelian Society, Volume 68, Issue 1, 1 June 1968, Pages 87–104, https://doi.org/10.1093/aristotel.