Histone acetylation has been recognized as an important post‐translational modification of core nucleosomal histones that changes access to the chromatin to allow gene transcription, DNA replication, and repair. Histone acetyltransferases were initially identified as co‐activators that link DNA‐binding transcription factors to the general transcriptional machinery. Over the years, more chromatin‐binding modes have been discovered suggesting direct interaction of histone acetyltransferases and their protein complex partners with histone proteins. While much progress has been made in characterizing histone acetyltransferase complexes biochemically, cell‐free (...) activity assay results are often at odds with in‐cell histone acetyltransferase activities. In‐cell studies suggest specific histone lysine targets, but broad recruitment modes, apparently not relying on specific DNA sequences, but on chromatin of a specific functional state. Here we review the evidence for general versus specific roles of individual nuclear lysine acetyltransferases in light of in vivo and in vitro data in the mammalian system. (shrink)

Acetylation of histones is an essential element regulating chromatin structure and transcription. MYST (Moz, Ybf2/Sas3, Sas2, Tip60) proteins form the largest family of histone acetyltransferases and are present in all eukaryotes. Surprisingly, until recently this protein family was poorly studied. However, in the last few years there has been a substantial increase in interest in the MYST proteins and a number of key studies have shown that these chromatin modifiers are required for a diverse range of cellular processes, both in (...) health and disease. Translocations affecting MYST histone acetyltransferases can lead to leukemia and solid tumors. Some members of the MYST family are required for the development and self‐renewal of stem cell populations; other members are essential for the prevention of inappropriate heterochromatin spreading and for the maintenance of adequate levels of gene expression. In this review we discuss the function of MYST proteins in vivo. (shrink)

Do individuals accept a moral point of view - if they are completely oriented towards their natural preferences and interests? The present article outlines the context of discussion concerning this question within moral philosophy and the social science. In addition it suggests a game-theoretical model with the help of which the question can be answered positively.

In this paper I will offer a comprehensive defense of the safety account of knowledge against counterexamples that have been recently put forward. In Sect. 2, I will discuss different versions of safety, arguing that a specific variant of method-relativized safety is the most plausible. I will then use this specific version of safety to respond to counterexamples in the recent literature. In Sect. 3, I will address alleged examples of safe beliefs that still constitute Gettier cases. In Sect. 4, (...) I will discuss alleged examples of unsafe knowledge. In Sect. 5, I will address alleged cases of safe belief that do not constitute knowledge for non-Gettier reasons. My overall goal is to show that there are no successful counterexamples to robust anti-luck epistemology and to highlight some major presuppositions of my reply. (shrink)

This book is a fiftieth anniversary republication of Thomas Nagel's "What Is It Like to Be a Bat?", a classic in the philosophy of mind. Through its argument for the irreducible subjectivity of consciousness, it played an essential role in making the study of consciousness a central part of philosophy, psychology, and neuroscience. It also spurred the now flourishing scientific attention to the consciousness of non-human creatures: mammals, birds, fish, mollusks, and insects. The book also includes a second essay (...) offering Nagel's more recent thoughts on the most promising positive response to the mind-body problem, as posed in the original essay. (shrink)

Formal principals are isolated to reveal a structure embedded in a wide range of studies, each of which partitions a domain of individuals into types and categories. It is thought that any reasonable theory of types should include these principles.

Descartes's epistemology, morals, and metaphysics – each offer reason to look on real life as a spectator looks on a theater production. The meditator seeking certainty watches his body move as in a dream and employs an entirely passive faculty of knowledge. In order to act firmly and yet not risk disappointment, the moral subject confines action to the soul, refusing to count bodily activities as actions, and cultivates a desire free from passion. After the Meditations, the metaphysician abandons the (...) thesis that soul and body constitute a human being, consequently limiting human goods to goods of the soul alone and devaluing embodied life in the world. (shrink)

CHAPTER Meta-View BRIDGES When I was a child, I lived in an area renowned for its many wooden covered bridges. Sometimes my family would take a Sunday drive ...

Separability is roughly the principle that, in comparing the value of two outcomes, one can ignore any people whose existence and welfare are unaffected. Separability is both antecedently plausible, at least as a principle of beneficence, and surprisingly powerful; it is the key to some of the best positive arguments in population ethics. This chapter surveys the motivations for and consequences of separability. In particular, it presents an ‘additivity theorem’ which explains how separability leads to total utilitarianism and closely related (...) axiological views. It then examines systematically how this family of views can avoid the Repugnant Conclusion by incorporating lexicality, a critical level, or a neutral range. (shrink)

v. 1. Editorial introduction -- v. 2. The English and Latin texts (i) -- v. 3. The English and Latin texts (ii).

Death.--The absurd.--Moral luck.--Sexual perversion.--War and massacre.--Ruthlessness in public life.--The policy of preference.--Equality.--The fragmentation of value.--Ethics without biology.--Brain bisection and the unity of consciousness.--What is it like to be a bat?--Panpsychism.--Subjective and objective.

In lieu of an abstract, here is a brief excerpt of the content:Journal of the History of Ideas 63.3 (2002) 371-397 [Access article in PDF] How the "New Science" of Cannons Shook up the Aristotelian Cosmos Mary J. Henninger-Voss [Figures]Approximately halfway through the "Second Day" of Galileo's Dialogue Concerning the Two Chief World Systems Galileo's mouthpiece, the mathematician Salviati, scoffs at his Aristotelian colleague Simplicio: "I see that you have hitherto been of that herd who, in order to learn (...) how matters such as this [motion] take place, and in order to acquire a knowledge of natural effects, do not betake themselves to ships or crossbows or cannons, but retire to their studies... to see whether Aristotle has said anything about them."1 Silly, simple Simplicio! He has been searching for natural philosophical wisdom in the books of natural philosophers rather than in the world of docks and arsenals. Indeed this quotation appears near the outset of Day Two wherein Salviati offers cannonshot as proof for the opposing Aristotelian position that the experience of projectiles proves the motionless state of the earth. Obviously, if the earth rotates toward the east, cannonballs shot point-blank to the west ought to travel much further than to the east. And clearly this is not so. Simplicio agrees that the new arguments offered by the cannon are excellent, "and now I see with how many elegant experiments nature graciously wishes to aid us in coming to the recognition of the truth," Simplicio enthusiastically enjoins. "What a shame there were no cannons in Aristotle's time!" exclaims the third interlocutor, Sagredo. "With them he would indeed have battered down ignorance, and spoken without [End Page 371] [Begin Page 373] the least hesitation concerning the universe."2 The irony here is not only that Aristotle might have used cannons in order to explain the workings of the universe but also that Galileo does so in the following pages. His demonstrations with reference to artillery demolish the Aristotelian position, but he has had Simplicio open the door for him by recognizing this most violent of artifices as an elegant experiment provided by nature.3The cannon provides a primary referent for Galileo's new mathematical physics of motion from his very first dialogue to his very last. The early De Motu culminated in a series of questions about the shot of cannons, while the conversation in his final masterwork, Discourses Concerning Two New Sciences, was set in the Venetian arsenal, and to it Galileo appended a table of the parabolic paths that could be expected from cannons shot at various elevations.4 In some sense Galileo turned inside-out a much older problem, one that had haunted military engineers of sixteenth-century Italy—and Galileo had been trained, and trained others, in military engineering.5 State organizers of war and captain generals were less interested in the implications the arts of fortifications and artillery held for the existing science of natural motion than in the necessity to reduce to a science, that is, a coherent body of knowledge, the rules for manufacturing cannons, planting artillery battery, aiming guns, and fortifying camps, cities, and castles.What Galileo gives us is recognizable as early physics, as a sophisticated mechanical science, a neat triumph of mathematical method in natural philosophy. But the ways and means by which mathematics came together with natural philosophy to address problems of both technology and nature are by no means neat. My claim is that attention to the military sphere will help us sort out some of those ways and means. The curious thing about the historiography on the relationship between early modern science and warfare is that the fact of a connection seems to have been taken for granted, while the implications have seldom been investigated.6 This essay is an attempt to trace those implications by [End Page 373] looking at a mathematician who specifically tried to reduce to a mathematical science the military arts, Niccolò Tartaglia.7 Tartaglia's story shows how the minutia of Aristotelian philosophy was transmuted in early attempts to understand cannonshot... (shrink)

Thomas Reid, the Scottish natural and moral philosopher, was one of the founding members of the Aberdeen Philosophical Society and a significant figure in the Scottish Enlightenment. Reid believed that common sense should form the foundation of all philosophical inquiry. He criticised the sceptical philosophy propagated by his fellow Scot David Hume and the Anglo-Irish bishop George Berkeley, who asserted that the external world did not exist outside the human mind. Reid was also critical of the theory of ideas (...) propagated by Locke and Descartes, arguing that it was incompatible with physical and experiential facts. For Reid, our senses demonstrate that the external world must exist, and this work is organised in chapters examining each of the senses in turn. The book, based on his lectures, was first published in 1764 when Reid was a regent professor at King's College, Aberdeen, and was reissued in 1818. (shrink)

Reprint of the ed. published by Viking Press, New York.

Issues of reliability are claiming center-stage in the epistemology of machine learning. This paper unifies different branches in the literature and points to promising research directions, whilst also providing an accessible introduction to key concepts in statistics and machine learning – as far as they are concerned with reliability.

Die Musik in den christlichen Gottesdiensten hat die Menschen zu allen Zeiten fasziniert und sie in Tiefen erreicht, die dem gesprochenen Wort verwehrt bleibt. Das II. Vatikanische Konzil hat diese Bedeutung der liturgischen Musik erkannt und ihren hohen Wert beschrieben. In der Fortführung dieser grundsätzlichen Würdigung stellt sich die vorliegende Arbeit den grundlegenden theologischen, spirituellen, und ästhetischen Fragen geeigneter gottesdienstlicher Musik. Im Gespräch mit der Religionsphilosophie Franz Rosenzweigs eröffnet sich nicht nur ein Blick in die Faszination jüdischen Denkens, gleichzeitig werden (...) die gemeinsamen liturgischen Wurzeln von Judentum und Christentum bewusst. Auf diesem Hintergrund können Kriterien entwickelt werden, die der Diskussion um eine angemessene, menschenzugewandte und traditionsverbundene Musik im Gottesdienst wertvolle Hilfe geben. (shrink)

The application of machine-learning technologies to medical practice promises to enhance the capabilities of healthcare professionals in the assessment, diagnosis, and treatment, of medical conditions. However, there is growing concern that algorithmic bias may perpetuate or exacerbate existing health inequalities. Hence, it matters that we make precise the different respects in which algorithmic bias can arise in medicine, and also make clear the normative relevance of these different kinds of algorithmic bias for broader questions about justice and fairness in healthcare. (...) In this paper, we provide the building blocks for an account of algorithmic bias and its normative relevance in medicine. (shrink)

The impassioned democratic voice of the Age of Revolution, Paine possessed a gift for stating complex ideas in concise language. This accessible collection of highlights from the social and political philosopher's best-known works includes lengthy selections from Common Sense , The American Crisis , The Rights of Man , and The Age of Reason.

Since Hilary Putnam offered multiple realization as an empirical hypothesis in the 1960s, philosophical consensus has turned against the idea that mental processes are identifiable with brain processes, and multiple realization has become the keystone of the 'antireductive consensus' across philosophy of science. Thomas W. Polger and Lawrence A. Shapiro offer the first book-length investigation of multiple realization, which serves as a starting point to a series of philosophically sophisticated and empirically informed arguments that cast doubt on the generality (...) of multiple realization in the cognitive sciences. They argue that mind-brain identities have played an important role in the growth and achievements of the cognitive sciences, and suggest that there is little prospect for multiple realization in an empirically-based theory of mind. This leads Polger and Shapiro to offer an alternative framework for understanding explanations in the cognitive sciences, as well as in chemistry, biology, and other non-basic sciences. (shrink)

This volume is a study of the influence of Timaeus on the development of Western cosmology in three axial periods of European culture: Late Antiquity, Middle Ages and Renaissance.

Thomas Reid saw the three subjects of logic, rhetoric, and the fine arts as closely cohering aspects of one endeavor that he called the culture of the mind. This was a topic on which Reid lectured for many years in Glasgow, and this volume presents as near a reconstruction of these lectures as is now possible. Though virtually unknown today, this material in fact relates closely to Reid's published works and in particular to the late Essays on the Intellectual (...) Powers of Man and Essays on the Active Powers of Man. When composing these works, Reid drew primarily on his lectures on "pneumatology," which presented a theory of the mental powers, broadly conceived. These lectures were basic to the course on the culture of the mind that explained the cultivation of the mental powers. Although the Essays also included some elements from the material on the culture of the mind, the bulk of the latter was left in manuscript form, and Alexander Broadie's edition restores this important extension of Reid's overall work. In addition, this volume continues the attractive combination of manuscript material and published work, in this case Reid's important and well-known essay on Aristotle's logic. This text was corrupted in earlier editions of Reid's works and is now restored to the state in which Reid left it. This volume underscores Reid's great and growing significance, viewed both as a historical figure and as a philosopher. At the same time, it is of great interdisciplinary importance. While the material emerges directly from the core of Reid's philosophy, as now understood, it will appeal widely to people in literary, cultural, historical, and communications studies. In this regard, the present volume is a true fruit of the Scottish Enlightenment. (shrink)

Thomas Reid , the Scottish natural and moral philosopher, was one of the founding members of the Aberdeen Philosophical Society and a significant figure in the Scottish Enlightenment. Reid believed that common sense should form the foundation of all philosophical inquiry. He criticised the sceptical philosophy propagated by his fellow Scot David Hume and the Anglo-Irish bishop George Berkeley, who asserted that the external world did not exist outside the human mind. Reid was also critical of the theory of (...) ideas propagated by Locke and Descartes, arguing that it was incompatible with physical and experiential facts. For Reid, our senses demonstrate that the external world must exist, and this work is organised in chapters examining each of the senses in turn. The book, based on his lectures, was first published in 1764 when Reid was a regent professor at King's College, Aberdeen, and was reissued in 1818. (shrink)

This paper gives a first theoretical formulation to a religious phenomenon which has not received much attention in philosophical discourse so far despite appearing in different highly heterogeneous religions. Vicarious religious ordinance refers to cases in which a living or deceased fully mature human being is knowingly or unknowingly assigned a religious affiliation without their consent or the consent of their dependents. I shall first offer three real-world examples of vicarious religious ordinance from Mormonism, Islam, and Shintoism and then raise (...) some normative concerns. I suggest (i) that vicarious religious ordinance does not fit neatly into current debates about religious epistemology, especially the recent debate on religious disagreement. I argue (ii) that normative questions as to why vicarious religious ordinance elicits indignation in its ‘victims’ is not easily explained through adducing similar examples. This paper aims to motivate further coordinated research on this topic. (shrink)

Thomas Reid is now recognized as one of the towering figures of the Enlightenment. Best known for his published writings on epistemology and moral theory, he was also an accomplished mathematician and natural philosopher, as an earlier volume of his manuscripts edited by Paul Wood for the Edinburgh Reid Edition, Thomas Reid on the Animate Creation, has shown. The Correspondence of Thomas Reid collects all of the known letters to and from Reid in a fully annotated form. (...) Letters already published by Sir William Hamilton and others have been reedited, and roughly half of the letters included appear in print for the first time. Writing in 1802, Reid's disciple and biographer Dugald Stewart doubted that Reid's correspondence &"would be generally interesting.&" This collection proves otherwise, for the letters illuminate virtually every aspect of Reid's life and career and, in some instances, provide us with invaluable evidence about activities otherwise undocumented in his manuscripts or published works. Through his correspondence we can trace Reid's relations with contemporaries such as David Hume and his colleagues at both King's College, Aberdeen, and the University of Glasgow, as well as his engagement with the most controversial philosophical, scientific, and political issues of his day. If anything, the letters assembled here serve as the starting point for understanding Reid and his place in the Enlightenment. (shrink)

In this book, T. M. Scanlon offers new answers to these questions, as they apply to the central part of morality that concerns what we owe to each other.

Cette étude essaye d’établir qu’il y a deux notions très différentes de « fondation » à l’œuvre dans les Recherches logiques de Husserl. Dans la IIIème Recherche, où le terme est formellement introduit, lorsqu’il se demande quels sont les contenus qui peuvent exister d’une manière autonome (indépendants) et lesquels peuvent exister uniquement en tant que moments d’autre chose (dépendants), Husserl suit ce que j’appelle un « modèle ontologique ». Selon ce modèle, le concret possède une priorité sur à l’abstrait qui (...) est fondé en lui. Dans la VIème Recherche, en revanche, Husserl s’oriente principalement sur un « modèle gnoséologique » qui voit le complexe comme fondé sur ce qui est relativement simple, étant donné que les expériences d’ordre supérieur (telles les perceptions de types d’objets plus complexes) sont « fondées sur » des expériences plus simples, bien qu’elles ne puissent pas y être réduites. L’exemple principal ici est celui des intuitions catégoriales : fondées sur les intuitions sensibles, elles n’y sont pas réductibles. Mais cette distinction entre deux sens différents du terme de « fondation » peut également nous aider à mieux comprendre de nombreuses thèses husserliennes plutôt controversées. Par exemple, elle peut nous permettre de mieux comprendre dans quelle mesure faire l’expérience d’un être humain comme un tout se fonde sur l’expérience d’un corps physique, et cela même si l’étant que nous rencontrons inclut à la fois des aspects corporels et des aspects spirituels – les deux étant vus, d’une manière essentielle, comme des moments de cette unique personne qui fait l’objet de notre expérience. (shrink)

In this essay, I exploit an ambiguity in the concept of self-determination. Self-de Green termination can mean to determine oneself in choices and actions or to determine one’s self. The second kind of self-determination leads to our capacity to imagine alternative selves of ourselves, which are to be actualized. This creates the basis for a normative conception of self-determination, i.e. a conception that incorporates the aspect of a right or good way to determine oneself. I defend a normative interpretation of (...) self-determination, which is illustrated by reference to three theorists: Harry Frankfurt, Thomas Hill Green and John Stuart Mill. (shrink)

Feeling good: four ways -- Finding that feeling -- The place of pleasure -- Knowing what's what -- Making things happen -- Being good -- Love and friendship -- Putting it together.

Metaphysical foundationalists argue that without fundamental facts, we cannot explain why there exist any dependent facts at all. Thus, metaphysical infinitism, the view that chains of ground can descend indefinitely without ever terminating in a level of fundamental facts, allegedly exhibits a kind of explanatory failure. I examine this argument and conclude that foundationalists have failed to show that infinitism exhibits explanatory failure. I argue that explaining the existence of dependent facts in terms of further dependent facts ad infinitum is (...) unproblematic by arguing for the plausibility of a ground-theoretic version of the Hume-Edwards Principle, which states that if each fact in a plurality of facts has a ground, then the plurality itself has a ground. (shrink)