In mice, dosage compensation of X‐linked gene expression is achieved through the inactivation of one of the two X‐chromosomes in XX female cells. The complex epigenetic process leading to X‐inactivation is largely controlled by Xist and Tsix, two non‐coding genes of opposing function. Xist RNA triggers X‐inactivation by coating the inactive X, while Tsix is critical for the designation of the active X‐chromosome through cis‐repression of Xist RNA accumulation. Recently, a plethora of trans‐acting factors and cis‐regulating elements have been suggested (...) to act as key regulators of either Xist, Tsix or both; these include ubiquitous factors such as Yy1 and Ctcf, developmental proteins such as Nanog, Oct4 and Sox2, and X‐linked regulators such as Rnf12. In this paper we summarise recent advances in our knowledge of the regulation of Xist and Tsix in embryonic stem (ES) and differentiating ES cells. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Reviewed by:A Historical Commentary on Arrian’s History of Alexander. Vol. II. Commentary on Books IV–VPhilip A. StadterBosworth, A. B. A Historical Commentary on Arrian’s History of Alexander. Vol. II. Commentary on Books IV–V. Oxford: Clarendon Press, 1995.In books 1–3, Arrian’s Alexander rushed from the Hellespont to Babylon, Susa, and Persepolis. In books IV and V the story changes: Alexander finds himself on the frontier, and beyond. No longer is (...) he confronting the enormous armies of the Persian king in set battles, but pushing beyond the frontiers of empire, seizing impregnable heights, and most important, struggling with his own Macedonians while defining himself.Bosworth, continuing his commentary after a fifteen-year interval, brings an exceptional background of historical, source critical, and literary studies. B. notes that his evaluation is “perhaps more sympathetic” than in his first volume, in part because the quality of the work “improves as it progresses” (v). The thoroughness [End Page 140] of the discussion (360 pages on the two books) is justified by the importance and complexity of the material. The reader is well served by an excellent subject index, a Greek index, ten maps, and four figures. An appendix on Nearchus suggests that that author may have reported much more than the journey from the Indus to the Persian Gulf found in the Indike, and may be a significant source for Arrian in the last four books of the Alexander history. Like the first volume, the commentary has Greek lemmata, translated only when there is a specific difficulty, but even Greekless readers can use it with the help of Brunt’s new Loeb text.Although the commentary deals frequently with textual questions, it focuses on elucidating the historical, geographical, stylistic, and interpretative problems of the text. B. ably notes the constant verbal reminiscences of Herodotus, Thucydides, and Xenophon, especially in the more elaborate passages, e.g., the speeches at the Hyphasis. Still more are undoubtedly to be found, such as the echo of Thucydides (1.110.1, 3.112.8, 87.87.6) in 5.27.6, ¹l¼goi ¨k poll©n. His elucidation of Arrian’s use of Megasthenes, Nearchus, and Eratosthenes in the digressions at the beginning of book 5 is a model of clarity and precision. Here as elsewhere he stresses Arrian’s purposeful blending of his sources: e.g., on 5.6.3–8: “It is an elaborately contrived passage, and the source material is carefully selected to fit the scheme of the argument. Arrian is not merely rewriting a passage of Eratosthenes.” Throughout, his comments on sources are precise and thoughtful.B.’s notes follow wherever the text leads, but he devotes special attention to the major focuses of Arrian’s attention: the great digression on Alexander’s orientalism, the murder of Cleitus, proskunesis, and the page’s conspiracy (4.7.4–14.4 5 45–101), the march to the Indus, with the siege of Massaga and the capture of Aornus (4.22.3–30.9 5 141–96), the series of digressions which begin book 5, (5.1.1–8.1 5 197–259), the battle on the Hydaspes against Porus (5.8.4–19.4 5 262–311), and the mutiny on the Hyphasis (5.24.8–29.5 5 337–60).Bosworth’s commentary on book 5 encompasses the multiple levels of the narrative: the reworking of Eratosthenes, Megasthenes, and Nearchus in the preliminary section; the topographical and tactical problems of the battle with Porus, and the rhetorical and stylistic subtleties of the debate at the Hyphasis. Throughout the book, Arrian shows Alexander going beyond his predecessors. By crossing the Indus he passes the limits of the Persian Empire. At Nysa he surpasses the mythical conquests of Dionysus (5.2.1). The digression on the Indus bridges recalls the bridges (and defeats) of Xerxes and Darius, as well as Roman imperial engineering (5.7.1–2). The crossing of the Hydaspes and great battle contrast with Cyrus’ disastrous battle with the Massagetae in Herodotus 1.204–14 (cf. 5.4.5). The description of the river systems of the Punjab (5.4.1–2) evokes Herodotus’ account... (shrink)

There is a view, expressed by some research ethics committees and health care professionals, that research should not, under any circumstance, be performed on dying patients. This paper begins to explore current attitudes towards palliative care research, although it becomes clear that the issues discussed apply to all fields of bio-medical research. Indeed the underlying principles of autonomy, non-maleficence, beneficence and justice should apply to all groups of human subjects involved across all areas of research. The ethical principles should apply (...) equally to healthy individuals as well as to those suffering from ill health, whether this be inherited or acquired, curable or terminal. (shrink)

In recent years, analytically trained philosophers have given extensive attention to various issues involved in the “culture wars,” including abortion, same-sex marriage, stem-cell research, and assisted suicide. There are, however, moral judgments that virtually no one questions. Defenses of adult-child sex, for example, are rare. There is also “conventional immorality”—the breach of conventional moral standards within roughly defined limits that at least limit the resulting damage to third parties and social institutions. These phenomena frame moral discussion even when, as often (...) happens, conventional people are in serious moral disagreement. In this essay I try to make sense of the phenomenon; in a subsequent essay I will show how conventional morality contains within itself the seeds of its collapse, and hence requires support from human nature, either rationally discovered or understood through revelation accepted in faith. (shrink)

Three experiments examine the effect of base rate consistency under direct experience. Base rate consistency was manipulated by blocking trials and setting base rate choice reinforcement to be either consistent or inconsistent across trial blocks. Experiment 1 shows that, contrary to the usual finding, participants use base rate information more than individuating information when it is consistent, but less when it is inconsistent. In Experiment 2, this effect was replicated, and transferred in verbal questions posed subsequently. Despite experience with consistent (...) base rates increasing sensitivity to base rates in word problems, verbal responses were far from normative. In Experiment 3, participants’ use of base rates was once again moderated by its consistency, but this effect was itself moderated by the diagnosticity of base rate information. Participants were highly accurate in estimating experienced base rates. These studies demonstrate that base rate usage is complex and a function of how base rates are presented (experienced versus summary statistics) and response format (choice proportions versus probability estimates). Knowledge of base rates was insufficient for proper usage in verbal word problems. Although choice proportions showed a sophisticated sensitivity to experienced base rate information, participants seemed unable to demonstrate a similar sophistication when given typical word problems indicating that base rate neglect is a function of information representation and not an inherent processing bias. (shrink)

In this book a non-realist philosophy of mathematics is presented. Two ideas are essential to its conception. These ideas are (i) that pure mathematics--taken in isolation from the use of mathematical signs in empirical judgement--is an activity for which a formalist account is roughly correct, and (ii) that mathematical signs nonetheless have a sense, but only in and through belonging to a system of signs with empirical application. This conception is argued by the two authors and is critically discussed by (...) three philosophers of mathematics. (shrink)

This thesis is concerned with Immanuel Kant's mature philosophy as a whole. My aim is to show the systematic relationship among Kant's three Critiques, and the continuity of these with the Inaugral Dissertation. I use recent interpretations of Kant's projects in the Critique of Pure Reason and I offer my own interpretation of the Critique of Judgment, in which I highlight the importance of the final Appendix in that work, to argue that the goal of these three works taken together (...) is to replace traditional metaphysics with a new approach entirely. In place of the traditional approach in which the principles of metaphysics are supposed to be principles of the objective order of things quite apart from the way they appear to us, Kant argues in favour of a system of subjective principles that he believes will nevertheless allow us to achieve the goals of metaphysics. The new metaphysics will not be knowledge-based, as traditional metaphysics had been. Rather Kant's system is primarily ethics-based. That is, the primary principles of Kant's metaphysical system are those of his rational ethics, which have the function of regulating our activity in, and organization of, the world. Instead of knowledge, ethics, and theology being uneasily coordinated parts of philosophy, as they are in traditional metaphysical systems, all three become integrated within an ethical, and essentially teleological, framework in Kant's system. Showing the role of the Critique of Judgment in bringing about this change, as well as showing the importance of teleology for Kant's philosophy, are both important goals of the thesis. (shrink)

New media are increasingly providing spaces and opportunities for media houses and activist groups engaged in socio-political reform in Africa. In Nigeria, social media are becoming platforms for communicating messages of resistance against oppressive political and exploitative economic power structures. This study analyzed Ogas at the top (OATT), an online puppetry series by Buni TV, as a way of examining new platforms and message content in Nigeria’s rapidly changing media sphere. Relying on semiotics and critical discourse analysis perspectives, the study (...) analyzed select episodes of the series, to gauge how producers constructed powerful visual and linguistic messages to boldly satirize social injustices perpetrated by Nigeria’s political elites. (shrink)

This article analyzes the phrase "corporate rule" and related expressions as they occur in the discourse of globalization. It argues that the cognitive dimension of conceptual figures depends substantially on the figures' rhetoricity. The analysis has three parts: conceptual metaphor analysis that considers metonymy, primary metaphors, and rhetoricity; rhetorical analysis that considers intensity, responsiveness, and the role of the utterer; and analysis of "licensing stories" that are formed through conceptual blending of The Developed World and The Developing World. This article (...) claims that rhetorical analysis is an important method for metaphor studies because it allows us to see connections between metaphoric expressions and relevant discourse and to recognize the patterns of variation that attend figurative expressions. (shrink)

Surveys the types of changes in mathematics that are of epistemological interest.