In normal human cells, a protein with a molecular weight of about 53,000 (p53) is present at a low level, detectable only by sensitive assays. When the cells are infected with some DNA tumour viruses or transformed by the same viruses, the amount of this protein increases dramatically, and much of it is found in a physical association with the virus‐coded protein that causes the transformation. The increase in amount and, incidentally, stability of p53 is not peculiar to virus‐transformed cells, (...) but also occurs in cells transformed by chemicals or radiation where there is no sign of any virus being involved (reviewed by Crawford).1 Cells in culture are not the same as cells in a patient, but these observations do raise questions about the possible involvement of p53 in human tumours. (shrink)

Numerous clinical, epidemiological and molecular findings link some types of Human Papillomaviruses (HPV) with cancer of the genital tract. They share a common pathway of transformation with a number of DNA tumour viruses, such as Adenovirus and SV40. Although all these viruses are termed ‘DNA tumour viruses’ and have similar in vitro transforming activities, Human Papillomavirus is the only one so far clearly involved in human cancer. Extensive studies on HPV E6 and E7 proteins have demonstrated their involvement in malignant (...) transformation. E6 and E7 bind the products of tumour suppressor genes, p53 and Rb1, respectively, modifying or inactivating their normal functions. The Rb1 and p53 genes are deleted or mutated in several cancers and both proteins regulate the transcription of genes involved in cell cycle progression control. The E6/p53 and E7/Rb1 interactions result in a deregulation of the cell cycle with loss of control of crucial cellular events, such as DNA replication, DNA repair and apoptosis. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:The Puzzle of Fanny PriceJoyce L. JenkinsIt is common to open a work regarding the merits of Mansfield Park by noting that Fanny Price is very difficult to like. Nietzsche might have described her as a "moral tarantula." 1 She sits, making negative moral judgments about the actions of others, while doing nothing herself. Fanny spends most of her time, literally, sitting or lying down. Austen describes her character (...) as "supine." Comparing Fanny with her sister Susan, Austen says that "Susan was only acting on the same truths, and pursuing the same system, which her [Fanny's] own judgment acknowledged, but which her more supine and yielding temper would have shrunk from asserting. Susan tried to be useful, where she could only have gone away and cried" (MP, p. 395). 2 And Fanny cries all of the time. She cries at least thirteen times over the course of the novel. So, there are two questions about the novel that need to be answered. Why did Austen create a heroine who is so clearly distasteful? Why do some critics and philosophers see Fanny as a moral ideal or cultural icon? Some (Alasdair MacIntyre, Gilbert Ryle, Lionel Trilling) argue that Fanny is so unappealing just because Austen wants to be didactic 3 and force us to focus on virtue. According to Lionel Trilling, for example, Mansfield Park has a different moral message from Pride and Prejudice. "Its praise is not for social freedom, but for social stasis. It takes full notice of spiritedness, vivacity, celerity and lightness, but only to reject them as having nothing to do with virtue and happiness, as being, indeed, deterrents to the good life." 4 Others think that the infelicities of the novel and its heroine make it a parody of traditional feminine values and conservative moral thought in general. 5 Here, I shall argue that a path between these two extreme ways of reading the novel is correct. I shall argue, using Alasdair MacIntyre's discussion as a starting [End Page 346] point, that Austen does not cast Fanny as a moral ideal. If Austen is Aristotelian (a common view among philosophers) Fanny cannot be an ideal. And, although I agree with Johnson's view that those who have read the novel as morally conservative are wrong, I do not think that the novel exhibits global skepticism about traditional standards for the beautiful/feminine. Austen condemns the idea that women should be passive dolls who do not think for themselves, but she does not parody the traditional idea that women should be sweet, gentle, and caring. In my view, Fanny's character constitutes a criticism of passivity, and of rigid adherence to moral rules.Alasdair MacIntyre's view is that Austen is an Aristotelian moralist with a Christian slant on the make-up of the virtues. He describes Fanny's character as an ideal of virtue. He argues that Fanny is pretty much lacking in charm just because Austen wanted to focus on the nature of virtue, which charm can obscure and which Fanny is meant to epitomize.For charm is the characteristically modern quality which those who lack or simulate the virtues use to get by in situations of characteristically modern social life... And the charm of an Elizabeth Bennett... may mislead us... Fanny is charmless; she has only the virtues, the genuine virtues to protect her... and when she disobeys her guardian, Sir Thomas Bertram, and refuses marriage to Henry Crawford it can only be because of what constancy requires. In so refusing she places the danger of losing her soul before the reward of gaining what for her would be a whole world. She pursues virtue for the sake of a certain kind of happiness and not for its utility. 6So, MacIntyre thinks that Fanny Price is meant to be a stripped down model of virtue, with constancy being the keystone virtue that she exhibits. "Constancy is crucial in at least two novels, Mansfield Park and Persuasion, in each of which it is a central virtue of the heroine... And without constancy all the other virtues to some degree lose their point" (AV, p. 242).But when constancy is discussed... (shrink)

Evidence of observed negative impacts on natural and human systems from anthropogenic climate change is increasing. However, human systems in particular are dynamic and influenced by multiple drivers and hence identifying an anthropogenic climate signal is challenging. Here we analyze the case of lake Palcacocha in the Andes of Peru, which offers a representative model for other glacier lakes and related risks around the world because it features a dynamic evolution of flood risk driven by physical and socioeconomic factors and (...) processes. Furthermore, it is the object of a prominent climate litigation case, wherein a local Peruvian citizen sued a large German energy producer over risk of flooding from lake Palcacocha. Adopting a conceptual model of cascading impacts and multiple drivers of risk, we first study climatic and other geophysical drivers of flood risk. We find that an anthropogenic signal from flood risk to greenhouse gas emissions is traceable. In parallel, flood risk has been strongly shaped (and increased) by interacting socioeconomic, institutional and cultural processes over the past few decades. The case raises important questions about the differentiation of responsibilities relating to flood risk of both global and local agents, which are, however, difficult to address in cases like Palcacocha, where we reveal a complex network of interlinked global, national and local drivers. Following from this, we outline a normative framework with a differentiated perspective on responsibility, implying that global emitters commit to support strengthening capacities in affected regions and localities and that local institutions and societies engage in local risk reduction measures and policies in collaboration with and driven by local communities. (shrink)

A decade in the making, the _Handbook i_s the definitive contemporary exposition of interpersonal psychoanalysis. It provides an authoritative overview of development, psychopathology, and treatment as conceptualized from the interpersonal viewpoint.

This book, collecting his most important papers in the form in which they were originally published, can be seen as a companion to that one.

There are growing discontinuities between the research practices of data science and established tools of research ethics regulation. Some of the core commitments of existing research ethics regulations, such as the distinction between research and practice, cannot be cleanly exported from biomedical research to data science research. Such discontinuities have led some data science practitioners and researchers to move toward rejecting ethics regulations outright. These shifts occur at the same time as a proposal for major revisions to the Common Rule—the (...) primary regulation governing human-subjects research in the USA—is under consideration for the first time in decades. We contextualize these revisions in long-running complaints about regulation of social science research and argue data science should be understood as continuous with social sciences in this regard. The proposed regulations are more flexible and scalable to the methods of non-biomedical research, yet problematically largely exclude data science methods from human-subjects regulation, particularly uses of public datasets. The ethical frameworks for Big Data research are highly contested and in flux, and the potential harms of data science research are unpredictable. We examine several contentious cases of research harms in data science, including the 2014 Facebook emotional contagion study and the 2016 use of geographical data techniques to identify the pseudonymous artist Banksy. To address disputes about application of human-subjects research ethics in data science, critical data studies should offer a historically nuanced theory of “data subjectivity” responsive to the epistemic methods, harms and benefits of data science and commerce. (shrink)

Deflationists about truth seek to undermine debates about the nature of truth by arguing that the truth predicate is merely a device that allows us to express a certain kind of generality. I argue that a parallel approach is available in the case of logical consequence. Just as deflationism about truth offers an alternative to accounts of truth's nature in terms of correspondence or justification, deflationism about consequence promises an alternative to model-theoretic or proof-theoretic accounts of consequence's nature. I then (...) argue, against considerations put forward by Field and Beall, that Curry's paradox no more rules out deflationism about consequence than the liar paradox rules out deflationism about truth. (shrink)

The general attributes of ecosystems are examined and a naturally occurring reference ecosystem is established, comparable with the isolated system of classical thermodynamics. Such an autonomous system with a stable, periodic input of energy is shown to assume certain structural characteristics that have an identifiable thermodynamic basis. Individual species tend to assume a state of least dissipation; this is most clearly evident in the dominant species (the species with the best integration of energy acquisition and conservation). It is concluded that (...) ecosystem structure results from the antagonistic interaction of two nearly equal forces. These forces have their origin in the Principle of Most Action (least dissipation or least entropy production) and the universal Principle of Least Action. Most action is contingent on the equipartitioning of the energy available, through uniform interaction of similar individuals. The trend to Least action is contingent on increased dissipation attained through increasing diversity and increasing complexity. These principles exhibit a basic asymmetry. Given the operation of these opposing principles over evolutionary time, it is argued that ecosystems originated in the vicinity of thermodynamic equilibrium through the resonant amplification of reversible fluctuations. On account of the basic asymmetry the system was able to evolve away from thermodynamic equilibrium provided that it remained within the vicinity of ergodynamic equilibrium (equilibrium maintained by internal work, where the opposing forces are equal and opposite).At the highest level of generalization there appear to be three principles operating: i) maximum association of free-energy and materials; ii) energy conservation (deceleration of the energy flow) through symmetric interaction and increased homogeneity; and iii) the principle of least action which induces acceleration of the energy flow through asymmetrical interaction. The opposition and asymmetry of the two forces give rise to natural selection and evolution. (shrink)

Surveys Western literature and thought to reveal the evolution of the ideals of sincerity and authenticity.

It has long been said that legislation ought to be knowable: accessible, comprehensible, and so forth. This is often described as an essential element of the rule of law. But in many legal systems, legislation has become so voluminous and complex that few people know its content. Rather than admit that the rule of law has been compromised, some scholars take legislative complexity as a provocation to rethink what the rule of law requires—and conclude that, for various reasons, the rule (...) of law can prevail even if legislation is not reasonably knowable to the people. This article responds to this line of scholarship and defends the orthodox position that the public ought to be able to understand legislation, or at least reasonably so. That is necessary to enable people to plan their lives in a way that properly reflects the role of legislation in contemporary administrative states. (shrink)

The central dispute between evidentialists and pragmatists about reasons for belief concerns whether or not non-evidential considerations can be reasons for belief. In recent work, some pragmatists about reasons for belief have made their case for pragmatism by appealing, in part, to a broad range of cases in which facts about one’s relationships with significant others (friends, romantic partners, and the like) appear to give one non-evidential reasons to have beliefs skewed in their favor. This chapter explores whether and how (...) such relationships might provide non-evidential reasons for belief. After first making the case against the evidentialist’s claim that there cannot be non-evidential reasons for belief, this chapter turns to examine different accounts of how our personal relationships might ground reasons for doxastic partiality. These are accounts on which reasons for doxastic partiality are grounded in facts about what attitudes are partly constitutive of being a good significant other to someone, and accounts on which reasons for doxastic partiality are grounded in reasons, more broadly, to benefit one’s significant others. This chapter argues that our personal relationships do not provide non-evidential reasons for belief, even if the pragmatist is right that there can be non-evidential reasons for belief. (shrink)

In _Real Natures and Familiar Objects_ Crawford Elder defends, with qualifications, the ontology of common sense. He argues that we exist -- that no gloss is necessary for the statement "human beings exist" to show that it is true of the world as it really is -- and that we are surrounded by many of the medium-sized objects in which common sense believes. He argues further that these familiar medium-sized objects not only exist, but have essential properties, which we (...) are often able to determine by observation. The starting point of his argument is that ontology should operate under empirical load -- that is, it should give special weight to the objects and properties that we treat as real in our best predictions and explanations of what happens in the world. Elder calls this presumption "mildly controversial" because it entails that arguments are needed for certain widely assumed positions such as "mereological universalism". Elder begins by defending realism about essentialness. He then defends this view of familiar objects against causal exclusion arguments and worries about vagueness. Finally, he argues that many of the objects in which common sense believes really exist, including artifacts and biological devices shaped by natural selection, and that we too exist, as products of natural selection. (shrink)

Sean Crawford; Discussions: In Defence of Object-Dependent Thoughts, Proceedings of the Aristotelian Society, Volume 98, Issue 1, 1 June 1998, Pages 201–210, ht.

This paper aims to call into question the customary division of logically revisionary responses to the truth-theoretic paradoxes into those that are “substructural” and those that are “ structural.” I proceed by examining, as a case study, Beall’s recent proposal based on the paraconsistent logic LP. Beall formulates his response to paradox in terms of a consequence relation that obeys all standard structural rules, though at the price of the language’s lacking a detaching conditional. I argue that the same response (...) to paradox can be given using a consequence relation that preserves detachment rules for a conditional, though at the price of restricting structural rules. The question “Is paradox being blocked by invoking a substructural consequence relation?” is thus ill-posed. The lesson of this example, I conclude, is that there is no useful explication of the idea of a substructural approach to paradox. (shrink)

Even if its constituent members still define particular positions and pursue at times somewhat independent policies, the EU acts increasingly in important areas as the unified federal state many have long wanted it to be. It may have come into being in response to practical problems, and pragmatic considerations are likely to ensure its continued consolidation, but its most committed champions have also presented it as the realization of an idea, as a longstanding project finally fulfilled. What is the idea (...) that a federal European state can claim to embody or represent or be animated by? How well do the various versions of the idea that have been articulated so far fit the current and emerging reality of the EU? Attention in the article focuses especially on the pan-European movement that emerged after the unprecedented destruction of World War I. (shrink)

This paper argues that typical biological species are natural kinds, on a familiar realist understanding of natural kinds—classes of individuals across which certain properties cluster together, in virtue of the causal workings of the world. But the clustering is far from exceptionless. Virtually no properties, or property-combinations, characterize every last member of a typical species—unless they can also appear outside the species. This motivates some to hold that what ties together the members of a species is the ability to interbreed, (...) others that it is common descent. Yet others hold that species are scattered individuals,of which organisms are parts rather than members. But not one of these views absolves us of the need to posit a typical phenotypic profile. Vagueness is here to stay. Some seek to explain the vagueness by saying species are united by “homeostatic property clusters”; but this view collapses into the more familiar realist picture. (shrink)

Innocence is a notion that can prove controversial. Claims of innocence typically support not imposing burdens on the innocent when their conduct is relevantly unobjectionable. This paper examines innocence in the context of violent conflict between states or groups. Many thinkers about the morality of such violence want to establish a principle that would protect innocent civilians. Yet the common view in just war theory does not affirm the moral innocence of civilians. Similarly, the common view that soldiers have an (...) equal right to kill does not affirm their equal moral culpability. (shrink)

According to commitment accounts of assertion, asserting is committing oneself to something’s being the case, where such commitment is understood in terms of norms governing a social practice. I elaborate and compare two version of such accounts, liability accounts (associated with C.S. Peirce) and dialectical norm accounts (associated with Robert Brandom), concluding that the latter are more defensible. I argue that both versions of commitment account possess a potential advantage over rival normative accounts of assertion in that they needn’t presuppose (...) any notion of an assertion’s correctness. Additionally, I show how dialectical norm accounts can explain relations between assertion and truth. After setting forth objections that have been raised against commitment accounts, I argue that responses are available on behalf of dialectical norm accounts. Finally, I propose that a liberalized dialectical norm account can illuminate phenomena sometimes seen as supporting truth relativism. (shrink)

This seminal work by political philosopher C.B. Macpherson was first published by the Clarendon Press in 1962, and remains of key importance to the study of liberal-democratic theory half-a-century later. In it, Macpherson argues that the chief difficulty of the notion of individualism that underpins classical liberalism lies in what he calls its "possessive quality" - "its conception of the individual as essentially the proprietor of his own person or capacities, owing nothing to society for them." Under such a conception, (...) the essence of humanity becomes freedom from dependence on the wills of others; society is little more than a system of economic relations; and political society becomes a means of safeguarding private property and the system of economic relations rooted in property. As the New Statesman declared: "It is rare for a book to change the intellectual landscape. It is even more unusual for this to happen when the subject is one that has been thoroughly investigated by generations of historians.... Until the appearance of Professor Macpherson's book, it seemed unlikely that anything radically new could be said about so well-worn a topic. The unexpected has happened, and the shock waves are still being absorbed." A new introduction by Frank Cunningham puts the work in a twenty-first-century context. (shrink)

What is it for a _belief_ to wrong someone? Views that have largely shaped the recent literature on doxastic wronging maintain that beliefs that wrong do so in virtue of _what_ is believed. This paper offers some criticisms of these views, as well as a contractualist alternative. On the view I defend here, beliefs can wrong when they stem from inferences licensed by principles to which others would have sufficiently weighty objections. Doxastic wronging, on this account, is not (or is (...) not entirely) a matter of having beliefs with certain kinds of objectionable representational content, but rather a matter of our being unable to _morally justify_ our beliefs to others. (shrink)

Most contemporary metaphysicians are sceptical about the reality of familiar objects such as dogs and trees, people and desks, cells and stars. They prefer an ontology of the spatially tiny or temporally tiny. Tiny microparticles 'dog-wise arranged' explain the appearance, they say, that there are dogs; microparticles obeying microphysics collectively cause anything that a baseball appears to cause; temporal stages collectively sustain the illusion of enduring objects that persist across changes. Crawford L. Elder argues that all such attempts to (...) 'explain away' familiar objects project downwards, onto the tiny entities, structures and features of familiar objects themselves. He contends that sceptical metaphysicians are thus employing shadows of familiar objects, while denying that the entities which cast those shadows really exist. He argues that the shadows are indeed really there, because their sources - familiar objects - are mind-independently real. (shrink)

Common sense believes in objects which, if real, routinely lose component parts or particles. Statues get chipped, people undergo haircuts and amputations, and ships have planks replaced. Sometimes philosophers argue that in addition to these objects, there are others which could not possibly lose any of their parts or particles, nor have new ones added to them--objects which could not possibly have been bigger or smaller, at any time, than how they actually were.1 (Sometimes the restriction on size is argued (...) independently of the restriction on switches of parts.2) If these other objects are real at all, they are alarmingly abundant. Exactly where the statue sits, there sits a parcel or piece of clay which would cease to be itself, and hence cease to exist, were even so small a part as the statue's nose removed.3 In exactly the place where the recently reconditioned ship is found, there is a mass of wood which never contained, and never could contain, any particles of wood--or bits of wood-stuff--other than those it now has.4 Moreover, since masses of matter (or "aggregates") can continue to exist even if divided into separate parts, while parcels cannot, the abundance is two-fold: where every parcel is found, there is also a mass.5 But how can there be room for all these additional objects if, at any time, two different objects cannot occupy exactly the same place? Or, worse, if even some of these additional objects are real, how can room remain for familiar objects? Recent treatments of this ancient puzzle have urged that we retain both "the principle of one object to a place" and the other ontological assumptions which make that principle seem to force a choice between affirming the reality of familiar objects, and that of the strangely brittle intruders.6 But all the recent treatments have left standing the reality of at least some of these brittle objects.7 By doing so they have passed up what is, perhaps, the simplest and safest response to the ancient puzzle.. (shrink)

Abstract According to Russellianism, the content of a Russellian thought, in which a person ascribes a monadic property to an object, can be represented as an ordered couple of the object and the property. A consequence of this is that it is not possible for a person to believe that a is F and not to believe b is F, when a=b. Many critics of Russellianism suppose that this is possible and thus that Russellianism is false. Several arguments for this (...) claim are criticized and it is argued that Russellians need not appeal to representational notions in order to defeat them. Contrary to popular opinion, the prospects for a pure Russellianism, a Russellianism without representations, are in fact very good. (shrink)

Based on specific documentary evidence, historian Lionel Jensen reveals how 16th- and 17th-century Western missionaries used translations of the ancient RU ...

En affirmant que "tout philosophe a deux philosophies : la sienne et celle de Spinoza", Bergson exprime avant tout que le philosophe se doit de rompre avec une pensée dogmatique qui n'a plus lieu d'être et que Spinoza incarne tout particulièrement. Le spinozisme manifeste la pente de l'intelligence lorsqu'elle suit sa logique propre sans être rectifiée par le recours à l'expérience. Or, c'est cette démarche systématique que la philosophie doit désormais abandonner. Bergson est néanmoins hanté par la pensée de Spinoza (...) et le rapport qu'il entretient avec lui, en particulier dans ses cours au Collège de France, met en évidence un lien bien plus complexe et subtil qu'un simple rapport d'opposition. Contre la tendance à la clôture et à la systématicité, Bergson va alors privilégier chez Spinoza la tendance à l'ouverture et au mysticisme. En mettant en lumière cet aspect, cet ouvrage montre la sympathie intellectuelle qui réunit ces penseurs autour des notions de joie et de liberté. C'est pourquoi la figure du Christ va constituer un modèle non seulement éthique mais ontologique. Le terme de mysticisme, chez ces deux auteurs, ne désigne ni le refus de l'expérience ni celui des sciences positives mais renvoie à un rationalisme élargi jusqu'à l'amour du réel."--Page 4 of cover. (shrink)

Dans cet article, nous analysons comment et dans quelle mesure les changements dans les modalités d’allocation des financements publics génèrent des transformations dans les pratiques, les temporalités et l’organisation de la recherche en histoire. Face aux deux thèses qui s’affrontent autour de cette problématique, l’une soutenant l’hypothèse de la déprofessionnalisation et de la perte d’autonomie des chercheurs, et l’autre celle d’une recomposition de la profession académique, le travail d’enquête réalisé dans trois laboratoires d’histoire en France montre qu’il n’y a pas (...) de modèle unique d’adaptation des équipes et des chercheurs par rapport à la montée en puissance des financements sur projet (FSP). La prise en compte du niveau organisationnel, avec ses spécificités contextuelles, se révèle essentielle pour saisir les modalités d’ajustement des laboratoires et des chercheurs face au renforcement des mécanismes de contractualisation. Par ailleurs, contrairement aux disciplines nécessitant des dispositifs expérimentaux coûteux, le niveau plus modeste des ressources mobilisées pour la conduite des recherches en histoire permet plus facilement aux historiens d’adopter une position de repli face aux FSP. Cette posture est également renforcée par le système de reconnaissance de la qualité académique propre au champ historiographique qui accorde une importance particulière au travail individuel et à l’investissement de longue durée. (shrink)