Poly(ADP‐ribosyl)ation is a post‐translational modification occurring in the nucleus. The most abundant and best‐characterized enzyme catalyzing this reaction, poly(ADP‐ribose) polymerase 1 (PARP1), participates in fundamental nuclear events. The enzyme functions as molecular “nick sensor”. It binds with high affinity to DNA single‐strand breaks resulting in the initiation of its catalytic activity. Activated PARP1 promotes base excision repair. In addition, PARP1 modifies several transcription factors and thereby precludes their binding to DNA. We propose that a major function of PARP1 includes the (...) silencing of transcription preventing expression of damaged genes. Concomitant stimulation of DNA repair suggests that PARP1 acts as a switch between transcription and DNA repair. Another PARP‐type enzyme, tankyrase, is involved in the regulation of telomere elongation. Tankyrase modifies a telomere‐associated protein and thereby prevents it masking telomeric repeats providing access of telomerase for telomere elongation. Therefore, poly(ADP‐ribosyl)ation reactions may act as molecular switches in DNA metabolism. BioEssays 23:543–548, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

This essay reconstructs the place of utopia in realist political theory, by examining the ways in which the literary genre of critical utopias can productively unsettle ongoing discussions about “how to do political theory.” I start by analyzing two prominent accounts of the relationship between realism and utopia: “real utopia” and “dystopic liberalism”. Elaborating on Raymond Geuss’s recent reflections, the essay then claims that an engagement with literature can shift the focus of these accounts. Utopian fiction, I maintain, is useful (...) for comprehending what is and for contemplating what might be. Ursula K. Le Guin’s novel The Dispossessed deploys this double function in an exemplary fashion: through her dynamic and open-ended portrayal of an Anarchist community, Le Guin succeeds in imagining a utopia that negates the status quo, without striving to construct a perfect society. The book’s radical, yet ambiguous, narrative hence reveals a strategy for locating utopia within realist political theory that moves beyond the positions dominating the current debate. Reading The Dispossessed ultimately demonstrates that realism without utopia is status quo–affirming, while utopia without realism is wishful thinking. (shrink)

Standard economic theory teaches that trade benefits all countries involved, at least in the long run. While there are other reasons for trade liberalization, this insight, going back to Ricardo's 1817 Principles of Political Economy , continues to underlie international economics. Trade also raises fairness questions. First, suppose A trades with B while parts of A's population are oppressed. Do the oppressed in A have a complaint in fairness against B? Should B cease to trade? Second, suppose because of oppression (...) or lower social standards, A's products are cheaper than B's. Can industries in B legitimately insist that their government take measures to help them compete? The Pauper-Labor Argument makes that case, and many economists enjoy dismissing it in undergraduate classes. Third, suppose A subsidizes its industries. If this lowers world market prices, does B have a fairness complaint against A? Ought countries to consider how trade policies affect others? This article is the first of two, which together develop a view that is meant to serve as a reference point for moral assessments of international trade policies. I develop this view by way of offering affirmative answers to these three questions. Since this discussion is organized around these three questions, the two studies can be read independently of each other. Key Words: the state • World Trade Organization • development • oppression • exploitation. (shrink)

Left-libertarian theories of justice hold that agents are full self-owners and that natural resources are owned in some egalitarian manner. Some philosophers find left-libertarianism promising because it seems that it coherently underwrites both some demands of material equality and some limits on the permissible means of promoting such equality. However, the main goal of this article is to argue that, as far as coherence is concerned, at least one formulation of left-libertarianism is in trouble. This formulation is that of Michael (...) Otsuka, who published it first in a 1998 article, and now in his thought-provoking book Libertarianism Without Inequality . In a nutshell, my objection is that the set of reasons that support egalitarian ownership of natural resources as Otsuka understands it stand in a deep tension with the set of reasons that would prompt one to endorse Otsuka’s right to self-ownership. In light of their underlying commitments, a defender of either of the views that left-libertarianism combines would actually have to reject the other. This incoherence, it seems, can only be remedied either by an approach that renders left-libertarianism incomplete in a way that can only be fixed by endorsing more commitments than most left-libertarians would want to or by an approach that leaves left-libertarianism a philosophically shallow theory. Key Words: equality • left-libertarianism • libertarianism • original appropriation • property • self-ownership. (shrink)

Mathias Frisch provides the first sustained philosophical discussion of conceptual problems in classical particle-field theories. Part of the book focuses on the problem of a satisfactory equation of motion for charged particles interacting with electromagnetic fields. As Frisch shows, the standard equation of motion results in a mathematically inconsistent theory, yet there is no fully consistent and conceptually unproblematic alternative theory. Frisch describes in detail how the search for a fundamental equation of motion is partly driven by pragmatic considerations (...) (like simplicity and mathematical tractability) that can override the aim for full consistency. The book also offers a comprehensive review and criticism of both the physical and philosophical literature on the temporal asymmetry exhibited by electromagnetic radiation fields, including Einstein's discussion of the asymmetry and Wheeler and Feynman's influential absorber theory of radiation. Frisch argues that attempts to derive the asymmetry from thermodynamic or cosmological considerations fail and proposes that we should understand the asymmetry as due to a fundamental causal constraint. The book's overarching philosophical thesis is that standard philosophical accounts that strictly identify scientific theories with a mathematical formalism and a mapping function specifying the theory's ontology are inadequate, since they permit neither inconsistent yet genuinely successful theories nor thick causal notions to be part of fundamental physics. (shrink)

Phillips argues that blindsight is due to response criterion artefacts under degraded conscious vision. His view provides alternative explanations for some studies, but may not work well when one considers several key findings in conjunction. Empirically, not all criterion effects are decidedly non-perceptual. Awareness is not completely abolished for some stimuli, in some patients. But in other cases, it was clearly impaired relative to the corresponding visual sensitivity. This relative dissociation is what makes blindsight so important and interesting.

Much has been written on the role of causal notions and causal reasoning in the so-called 'special sciences' and in common sense. But does causal reasoning also play a role in physics? Mathias Frisch argues that, contrary to what influential philosophical arguments purport to show, the answer is yes. Time-asymmetric causal structures are as integral a part of the representational toolkit of physics as a theory's dynamical equations. Frisch develops his argument partly through a critique of anti-causal arguments and (...) partly through a detailed examination of actual examples of causal notions in physics, including causal principles invoked in linear response theory and in representations of radiation phenomena. Offering a new perspective on the nature of scientific theories and causal reasoning, this book will be of interest to professional philosophers, graduate students, and anyone interested in the role of causal thinking in science. (shrink)

This paper provides a survey of several philosophical issues arising in classical electrodynamics arguing that there is a philosophically rich set of problems in theories of classical physics that have not yet received the attention by philosophers that they deserve. One issue, which is connected to the philosophy of causation, concerns the temporal asymmetry exhibited by radiation fields in the presence of wave sources. Physicists and philosophers disagree on whether this asymmetry reflects a fundamental causal asymmetry or is due to (...) statistical or thermodynamic considerations. I suggest that an explanation appealing to the asymmetry of causation is more promising. Another issue concerns the conceptual structure of the theory. Despite its empirical success, classical electrodynamics faces serious foundational problems. Models of charged particles involve what by the theory's own lights are idealizations, I maintain, and this is a feature that is not readily captured by traditional philosophical accounts of scientific theories. Other issues I discuss concern (i) the relation between Lorentz's theory of the electron and Einstein's Theory of Special Relativity; (ii) the notion of the domain of a theory, the question of theory reduction, and the relation between classical and more fundamental quantum theories; and (iii) the role of locality constraints, their relation to the concept of causation; and the status of locality conditions in the semi-classical theory of the Aharanov-Bohm effect. (shrink)

The associative theory of creativity states that creativity is associated with differences in the structure of semantic memory, whereas the executive theory of creativity emphasises the role of top-down control for creative thought. For a powerful test of these accounts, individual semantic memory structure was modelled with a novel method based on semantic relatedness judgements and different criteria for network filtering were compared. The executive account was supported by a correlation between creative ability and broad retrieval ability. The associative account (...) was independently supported, when network filtering was based on a relatedness threshold, but not when it was based on a fixed edge number or on the analysis of weighted networks. In the former case, creative ability was associated with shorter average path lengths and higher clustering of the network, suggesting that the semantic networks of creative people show higher small-worldness. (shrink)

David Albert and Barry Loewer have argued that the temporal asymmetry of our concept of causal influence or control is grounded in the statistical mechanical assumption of a low-entropy past. In this paper I critically examine Albert's and Loewer 's accounts.

Priority setting in health care is ubiquitous and health authorities are increasingly recognising the need for priority setting guidelines to ensure efficient, fair, and equitable resource allocation. While cost-effectiveness concerns seem to dominate many policies, the tension between utilitarian and deontological concerns is salient to many, and various severity criteria appear to fill this gap. Severity, then, must be subjected to rigorous ethical and philosophical analysis. Here we first give a brief history of the path to today’s severity criteria in (...) Norway and Sweden. The Scandinavian perspective on severity might be conducive to the international discussion, given its long-standing use as a priority setting criterion, despite having reached rather different conclusions so far. We then argue that severity can be viewed as a multidimensional concept, drawing on accounts of need, urgency, fairness, duty to save lives, and human dignity. Such concerns will often be relative to local mores, and the weighting placed on the various dimensions cannot be expected to be fixed. Thirdly, we present what we think are the most pertinent questions to answer about severity in order to facilitate decision making in the coming years of increased scarcity, and to further the understanding of underlying assumptions and values that go into these decisions. We conclude that severity is poorly understood, and that the topic needs substantial further inquiry; thus we hope this article may set a challenging and important research agenda. (shrink)

In legal academia it is highly controversial how to ‘be original’ in legal research. This article will try to maintain an attitude of tolerance in not promoting or discrediting one particular methodology. Instead, it will identify four different ways of ‘being original’. Perhaps the most common approach is to deal with ‘micro-legal questions’. Many legal academics also pursue research in ‘macro-legal questions’. Less common but growing is the importance of ‘scientific legal research’ and research in ‘non-legal topics’.

Research on preference reversals has demonstrated a disproportionate influence of outcome probability on choices between monetary gambles. The aim was to investigate the hypothesis that this is a prominence effect originally demonstrated for riskless choice. Another aim was to test the structure compatibility hypothesis as an explanation of the effect. The hypothesis implies that probability should be the prominent attribute when compared with value attributes both in a choice and a preference rating procedure. In Experiment 1, two groups of undergraduates (...) were presented with medical treatments described by two value attributes (effectiveness and pain-relief). All participants performed both a matching task and made preference ratings. In the latter task, outcome probabilities were added to the descriptions of the medical treatments for one of the groups. In line with the hypothesis, this reduced the prominence effect on the preference ratings observed for effectiveness. In Experiment 2, a matching task was used to demonstrate that probability was considered more important by a group of participating undergraduates than the value attributes. Furthermore, in both choices and preference ratings the expected prominence effect was found for probability. (shrink)

This volume contains five articles by prominent scholars of French literature and political philosophy that examine the relation between Montaigne's Essays, one ...

I criticize two accounts of the temporal asymmetry of electromagnetic radiation - that of Huw Price, whose account centrally involves a reinterpretation of Wheeler and Feynman's infinite absorber theory, and that of Dieter Zeh. I then offer some reasons for thinking that the purported puzzle of the arrow of radiation does not present a genuine puzzle in need of a solution.

This book provides a formal ontology of senses and the belief-relation that grounds the distinction between de dicto, de re, and de se beliefs as well as the opacity of belief reports. According to this ontology, the relata of the belief-relation are an agent and a special sort of object-dependent sense (a "thought-content"), the latter being an "abstract" property encoding various syntactic and semantic constraints on sentences of a language of thought. One bears the belief-relation to a thought-content T just (...) in case one (is disposed as one who) inwardly affirms a certain sentence S of one’s language of thought that satisfies what T encodes, which in turn requires that S’s non-logical parts stand in appropriate semantical relations to items specified by T. Since these items may include other senses as well as ordinary objects, beliefs of arbitrary complexity are automatically accommodated. Within the framework of the formal ontology, a context-dependent compositional semantics is then provided for a fragment of regimented English capable of formulating ascriptions of belief—a semantics that treats substitutional opacity as a genuine semantic datum. Finally, the resulting picture of belief and its attribution is defended by showing how it solves standard puzzles, avoids objections to rival accounts, and satisfies certain adequacy conditions not fulfilled by traditional theories. Along the way, clarification and defense is offered for the ingredient conception of object-dependent senses, and it is shown how adoption of the language of thought hypothesis permits Bertrand Russell’s obscure doctrine of logical forms to be understood in a way that not only vindicates his Multiple Relation theory of de re belief but also reveals the connection between these logical forms and thought-contents. (shrink)

I show that the standard approach to modeling phenomena involving microscopic classical electrodynamics is mathematically inconsistent. I argue that there is no conceptually unproblematic and consistent theory covering the same phenomena to which this inconsistent theory can be thought of as an approximation; and I propose a set of conditions for the acceptability of inconsistent theories.

Volume 52, Issue 6, June - July 2020, Page 602-612.

This paper sheds light on the main issue of this book by affording a side look at a discipline other than economics, namely political theory. It is argued that the contemporary debate in political theory hinges on the question of 'realism'. Through a discussion of Raymond Geuss's work, the paper seeks to show that political theory remains caught between the conflicting requirements of deep contextual analysis and radically critical engagement with the world 'as it is'. Finally, the idea of a (...) 'division of labour' between contextualist and critical approaches to political theory is introduced. (shrink)

ALTHOUGH majority rule finds ready acceptance whenever groups make decisions, there are surprisingly few philosophically interesting arguments in support of it.1 Jeremy Waldron’s The Dignity of Legislation contains the most interesting recent defense of majority rule. Waldron combines his own argument from respect with May’s influential characterization of majority rule, tying both to a reinterpretation of a well-known passage from Locke’s Second Treatise (“the body moves into the direction determined by the majority of forces”). Despite its impressive resourcefulness, Waldron’s defense (...) is deficient, and one goal of this essay is to show how. Yet our main concern is not to criticize Waldron, but to demonstrate general deficiencies of arguments for majority rule and to suggest a strategy for a more adequate and more complete defense. Such arguments tend to have one of two weaknesses: Either they assume that collective decisionmaking is done in terms of ranking options and thus neglect both aggregation methods using more information than the relative standing of options in rankings (such as so-called positional methods) and rules that are not aggregation methods at all (such as fair-division procedures); or they also constitute arguments for other decision rules. In the first case, the argument is too narrow, in the second it is too broad. The narrowness problem is bigger than stated so far because arguments for majority rule tend to assume not only that decisions are made by ranking options, but also that only two options are to be ranked. Both problems arise for Waldron’s defense and leave it incomplete. Yet such incompleteness also characterizes the state of the art in arguing for majority rule. So in addition to.. (shrink)

In Frisch 2004 and 2005 I showed that the standard ways of modeling particle-field interactions in classical electrodynamics, which exclude the interactions of a particle with its own field, results in a formal inconsistency, and I argued that attempts to include the self-field lead to numerous conceptual problems. In this paper I respond to criticism of my account in Belot 2007 and Muller 2007. I concede that this inconsistency in itself is less telling than I suggested earlier but argue that (...) existing solutions to the theory's foundational problems do not support the kind of traditional philosophical conception of scientific theorizing defended by Muller and Belot. *Received January 2007; revised October 2007. †To contact the author, please write to: Department of Philosophy, University of Maryland, Skinner Building, College Park, MD 20742; e-mail: [email protected]. (shrink)

Volume 20, Issue 7, July 2020, Page W17-W19.

As the record-breaking heat of 2016 continues into 2017, making it likely that 2017 will be the second hottest year on record just behind the El Niño year 2016, and as Arctic heat waves pushing the sea ice extent to record lows are mirrored by large scale sheets of meltwater and even rain in Antarctica—the Trump administration is taking dramatic steps to undo the Obama administration’s climate legacy.In its final years, the Obama administration pursued two principal strategies toward climate policy. (...) First, by signing the Paris Accord it committed the U.S. to contribute to global efforts to hold “the increase in the global average temperature to well below 2°C above pre-industrial levels and to pursue efforts to... (shrink)

The practical goal of preventing premature death seems uncontroversial. But the term ‘premature death’ is vague with several, sometimes conflicting definitions. This ambiguity results in several conceptions with which not all will agree. Moreover, the normative rationale behind the goal of preventing premature deaths is masked by the operational definition of existing measures. In this article, we argue that ‘premature death’ should be recognized as a normative concept. We propose that normative theories should be used to justify measures of premature (...) death to provide them with normative validity and public legitimacy. (shrink)

Working in Z + KP, we give a new proof that the class of hereditarily finite sets cannot be proved to be a set in Zermelo set theory, extend the method to establish other failures of replacement, and exhibit a formula Φ(λ, a) such that for any sequence $\langle A_{\lambda} \mid \lambda \text{a limit ordinal} \rangle$ where for each $\lambda, A_{\lambda} \subseteq ^{\lambda}2$ , there is a supertransitive inner model of Zermelo containing all ordinals in which for every λ A (...) λ = {α ∣Φ(λ, a)}. (shrink)

La traduction de la métaphore théâtrale goffmanienne en France a induit un déplacement théorique au coeur de son œuvre. Elle a exagéré le caractère dramaturgique des interactions, laissant de côté certaines nuances initiales. Une relecture du texte anglais remet la métaphore à sa place et en fait un instrument analytique pour les sciences sociales. Nous proposons de repenser cet instrument à partir de l’étude de l’improvisation théâtrale, dont pourrait découler un modèle qui tient compte de l’indétermination dans la dynamique des (...) interactions. (shrink)

This article highlights the continuing relevance of a classic bioethical text, “Bioethics as a Discipline,” published by the Hastings Center’s cofounder Daniel Callahan in 1973. Connecting the text’s programmatic recommendations with later reflections and interventions Callahan wrote about the development of bioethics illuminates how the vision Callahan established and the reality this vision helped create were interrelated—just not in the way Callahan had hoped for. Although this portrait relies on an individual perception of the development of bioethics, it might nevertheless, (...) through its unique linkage of different bioethical temporalities, contribute to a broader reassessment of what bioethics became and why. (shrink)

One of the core tenets of cognitive metaphor theory is the claim that metaphors ground abstract knowledge in concrete, first-hand experience. In this paper, I argue that this grounding hypothesis contains some problematic conceptual ambiguities and, under many reasonable interpretations, empirical difficulties. I present evidence that there are foundational obstacles to defining a coherent and cognitively valid concept of “metaphor” and “concrete meaning,” and some general problems with singling out certain domains of experience as more immediate than others. I conclude (...) from these considerations that whatever the facts are about the comprehension of individual metaphors, the available evidence is incompatible with the notion of an underlying conceptual structure organized according to the immediacy of experience. (shrink)

Sequences of numbers representing prior resource size were presented to participants in a common-pool resource dilemma. The numbers were sampled from uniform probability distributions with either a low variance (low resource uncertainty) or a high variance (high resource uncertainty). Presentations were both sequential and simultaneous. Three groups of 16 undergraduates either estimated the size of the resource when it did not represent value to them; requested an amount from the resource, identified with a sum of money, when the outcome of (...) the requests only depended on resource size; or requested from the resource (sum of money) when the outcome of the requests depended on both resource size and how much others in a group requested. In support of an individual outcome-desirability bias due to selective recall of the number sequences, after sequential presentation larger requests were observed when resource uncertainty was high than when it was low. No effects of resource uncertainty or presentation were found on the estimates of resource size. Whether or not the outcome of the requests depended on others' requests made little difference. (shrink)

After critical appraisal of mathematical and biological characteristics of the model, we discuss how a classical hippocampal neural network expresses functions similar to those of the chaotic model, and then present an alternative stimulus-driven chaotic random recurrent neural network (RRNN) that learns patterns as well as sequences, and controls the navigation of a mobile robot.

After accounting for the festival as a philosophical theme across Heidegger’s early to later writings, this article summarizes the 1943 “Andenken” essay on Hölderlin’s “wedding festival” and 1959 “Hölderlin’s Earth and Heaven” essay on the “round dance.” It then explores how these motifs of the wedding festival and its round dance are in play in the 1936–1937 Contributions to Philosophy: Of the Event manuscript, especially in its philosophy of attunement, and notion of the “celebration of the last god.”.