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)

We recently examined gene expression during Xenopus tadpole tail appendage regeneration and found that carbohydrate regulatory genes were dramatically altered during the regeneration process. In this essay, we speculate that these changes in gene expression play an essential role during regeneration by stimulating the anabolic pathways required for the reconstruction of a new appendage. We hypothesize that during regeneration, cells use leptin, slc2a3, proinsulin, g6pd, hif1α expression, receptor tyrosine kinase (RTK) signaling, and the production of reactive oxygen species (ROS) to (...) promote glucose entry into glycolysis and the pentose phosphate pathway (PPP), thus stimulating macromolecular biosynthesis. We suggest that this metabolic shift is integral to the appendage regeneration program and that the Xenopus model is a powerful experimental system to further explore this phenomenon.Also watch the Video Abstract. (shrink)

Juros, H. Die "Objektschwäche" der Moraltheologie.--Nossol, A. Christsein als radikale Proexistenz.--Styczen', T. Personaler Glaube im Spannungsfeld von religiöser Autorität und Gewissensautonomie.--Piegsa, J. Die "Sache Jesu" und die Reformmarxisten.--Szostek, A. Zur gegenwärtigen Diskussion über den Utilitarismus.--Pryszmont, J. Die Wiederherstellung der gefallenen menschlichen Natur.--Theiner, J. Gedanken zur Sündenlehre Abaelards in seinem Werk "Ethica seu Scito teipsum".--Sikorski, T. Die Aporie des gemeinschaftlichen Lebens.--Kleber, K.-H. Der Christ und die Armut.--Wojtyła, K. Die menschliche Person im Kontext der ehelichen Hingabe und Elternschaft.--Tischner, J. Überlegungen zur Arbeitsethik.--Zeimentz, (...) H. Toleranz-Freiheit-Wahrheit. (shrink)

Zwischen den Schriften "Was ist Metaphysik?", " Vom Wesen des Grundes", "Kant und das Problem der Metaphysik", 1929, und "Platons Lehre von der Wahrheit", 1942, hat Heidegger nichts publiziert außer zwei kurzen Hölderlin-Vorträgen und seiner Rektoratsrede von 1933. In diesen dreizehn Jahren hat sowohl Heideggers Denkansatz als auch seine Denkhaltung eine Veränderung erfahren; es ist die in der Heidegger-Forschung so genannte "Kehre". Seit der 1976 aus dem Nachlaß begonnenen Herausgabe von Heideggers Vorlesungen fällt von Mal zu Mal mehr Licht auf (...) seinen Denkweg in besagter Zeitspanne. Zu Recht wurde die Vorlesung als die "Heideggers philosophisches Schaffen zentral prägende Darstellungsform" bezeichnet. Studiert man die Vorlesungen, so wird klar, wie es dazu kommt, daß Heideggers Denkwege in dieser Zeit oft "jäh im Unbegangenen aufhören"; so das Motto des Buches "Holzwege", das, 1950 erschienen, Vorträge und Aufsätze aus der Zeit von 1935 bis 1946 enthält.Die These der Autorin lautet: Der Grund für Heideggers gewandeltes Denken am Ende der genannten Zeitspanne besteht in Erfahrungen, die er im Gespräch mit Hölderlin seit der Vorlesung von 1934/35 gemacht hat. Was sich zwischen 1934/35 und der Heraklit-Vorlesung von 1944 abspielt und als "Kehre" angesprochen wird, bereitet Heideggers Denken vor, wie es in "Vorträge und Aufsätze", "Unterwegs zur Sprache" und in allen späteren Schriften zum Ausdruck kommt.Die Vorlesungen ab 1934/35 zeigen drei Schwerpunkte: die Auseinandersetzung mit Hölderlin, mit Nietzsche und mit den griechischen Denkern am Anfang der abendländischen Geschichte. Während die Philosophie Nietzsches in Heideggers Augen die Vollendung des mit Platon beginnenden Zeitalters der Metaphysik artikuliert, kündigt sich in der Dichtung Hölderlins der Anfang einer anderen Geschichte an. Diesen anderen Geschichtsanfang sieht Heidegger in einem Spannungsverhältnis zu dem, was die griechischen anfänglichen Denker gesagt haben. Ihre Gedanken legt er als ein Sprechen aus dem Erfahrungsbereich der Ἀλήθεια aus. Hölderlin und die Ἀλήθεια stehen also, in je verschiedener, jedoch aufeinander bezogener Weise, für den Anfang von Geschichte. Es ist Heideggers Überzeugung, daß sich Geschichte aus ihrem Anfang bleibend bestimmt. In der Untersuchung wird die Herkunft dieser Überzeugung aufgespürt, was auch irn Hinblick auf die unveröffentlichte Abhandlung von 1941 "Über den Anfang" von Bedeutung ist.Die Verfasserin legt den Boden frei, aus dem das Denken von Heideggers Spätschriften erwächst. Dazu analysiert sie die Freiburger Vorlesungen zwischen 1934/35 und 1944. Es geht ihr darum, die zentralen Gedanken Heideggers in statu nascendi und in ihrer Entfaltung, in ihrer Kontinuität und Veränderung zu verfolgen. Eine solche Verfahrensweise ist um so mehr geboten, als in vielen bisherigen Forschungsarbeiten der Wegcharakter von Heideggers Denken nicht ernst genommen wird und frühere Positionen mit späteren unachtsam vermischt werden. Beachtet man dagegen das Weghafte dieses Denkens, so kann eine Reihe gängiger Forschungsmeinungen korrigiert werden. Zum Beispiel tritt die Zeit-Thematik in Heideggers Spätphilosophie keineswegs "deutlich in den Hintergrund", sie hält sich vielmehr unter gewandelten Namen bis ans Ende seines Denkweges durch. (shrink)

Antoine Berman became well known for his contribution to translation studies with his ’thirteen deformation tendencies’, recognized as his major work and published in 1985. This article sustains that in 1983, in the text Bildung et Bildungsroman, Berman found the fundamentals for his theory in the German Bildung. The cultural formation of mankind as the emergence to humankind and the translation as one of its principal agents, therefore, manifests its centrality for Berman ́s proposal of translation as a shelter of (...) the far-away (l ́auberge du lointain). (shrink)

This work has been selected by scholars as being culturally important, and is part of the knowledge base of civilization as we know it. This work was reproduced from the original artifact, and remains as true to the original work as possible. Therefore, you will see the original copyright references, library stamps (as most of these works have been housed in our most important libraries around the world), and other notations in the work. This work is in the public domain (...) in the United States of America, and possibly other nations. Within the United States, you may freely copy and distribute this work, as no entity (individual or corporate) has a copyright on the body of the work. As a reproduction of a historical artifact, this work may contain missing or blurred pages, poor pictures, errant marks, etc. Scholars believe, and we concur, that this work is important enough to be preserved, reproduced, and made generally available to the public. We appreciate your support of the preservation process, and thank you for being an important part of keeping this knowledge alive and relevant. (shrink)

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)

The grounds of justice -- "Un pouvoir ordinaire": shared membership in a state as a ground of -- Justice -- Internationalism versus statism and globalism: contemporary debates -- What follows from our common humanity? : the institutional stance, human rights, and nonrelationism -- Hugo Grotius revisited : collective ownership of the Earth and global public reason -- "Our sole habitation" : a contemporary approach to collective ownership of the earth -- Toward a contingent derivation of human rights -- Proportionate use (...) : immigration and original ownership of the Earth -- "But the earth abideth for ever" : obligations to future generations -- Climate change and ownership of the atmosphere -- Human rights as membership rights in the global order -- Arguing for human rights : essential pharmaceuticals -- Arguing for human rights : labor rights as human rights -- Justice and trade -- The way we live now -- "Imagine there's no countries" : a reply to John Lennon -- Justice and accountability : the state -- Justice and accountability : the World Trade Organization. (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.

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)

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)

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)

Speech planning is a sophisticated process. In dialog, it regularly starts in overlap with an incoming turn by a conversation partner. We show that planning spoken responses in overlap with incoming turns is associated with higher processing load than planning in silence. In a dialogic experiment, participants took turns with a confederate describing lists of objects. The confederate’s utterances (to which participants responded) were pre‐recorded and varied in whether they ended in a verb or an object noun and whether this (...) ending was predictable or not. We found that response planning in overlap with sentence‐final verbs evokes larger task‐evoked pupillary responses, while end predictability had no effect. This finding indicates that planning in overlap leads to higher processing load for next speakers in dialog and that next speakers do not proactively modulate the time course of their response planning based on their predictions of turn endings. The turn‐taking system exerts pressure on the language processing system by pushing speakers to plan in overlap despite the ensuing increase in processing load. (shrink)

The creativity literature is replete with dualistic constructs, suggesting shared mechanisms but also tempting overinterpretation of their interrelations. An explicit list of relevant concept associations indicates substantial commonality, yet also exposes certain inconsistencies. Dual-process accounts (A and B is relevant) hold promise in resolving discrepancies to the extent that we understand the relative contributions and conditions of A and B.

Aratus has been notorious for his wordplay since the first decades of his reception. Hellenistic readers such as Callimachus, Leonidas, or ‘King Ptolemy’ seem to have picked up on the pun on the author's own name atPhaenomena2, as well as on the famous λεπτή acrostic atPhaen.783–6 that will be revisited here. Three carefully placed occurrences of the adjective have so far been uncovered in the passage, but for a full appreciation of its elegance we must note that Aratus has set (...) his readers up to notice a fourth. (shrink)

In a recent extended essay, philosopher Daniel Hausman goes a long way towards dismissing severity as a morally relevant attribute in the context of priority setting in healthcare. In this response, we argue that although Hausman certainly points to real problems with how severity is often interpreted and operationalised within the priority setting context, the conclusion that severity does not contain plausible ethical content is too hasty. Rather than abandonment, our proposal is to take severity seriously by carefully mapping the (...) possibly multiple underlying accounts to well-established ethical theories, in a way that is both morally defensible and aligned with the term’s colloquial uses. (shrink)

Evolutionary or biocultural theorizing about horror films has been slow to gain traction in film studies, but the field has seen two recent book publications, Mastering Fear by Rikke Schubart and Primal Roots of Horror Cinema by Carrol L. Fry. Unfortunately, neither book is poised to make a substantial impact on evolutionary horror film theory. Mastering Fear ultimately undermines its own engagement with evolutionary social science, and Primal Roots of Horror Cinema stops short of contributing substantially to the field beyond (...) its compelling argument for the relevance of evolutionary social science to film studies. Plenty of work remains to be done at the fertile junction between evolutionary psychology and horror film. (shrink)

We argue that the two temporal cognition systems are conceptually too confined to be helpful in understanding the evolution of temporal cognition. In fact, we doubt there are two systems. In relation to this, we question that the authors did not describe the results of our planning study on ravens correctly, as this is of consequence to their theory.

This article outlines different attempts to define integrity, and argues, with reference to the theory of moral particularism, that definitions acquire universal applicability at the expense of their informative value. The article then proceeds to more delimitating definitions that emphasise the social aspect, and argues that their ideas of the concept, like courage, require certain situations in order to unfold. Since not every person is challenged to act with integrity, the delimitation requires a distinction between manifest integrity and dormant integrity, (...) or dormant lack of integrity. Persons of influence, like politicians and managers, on the other hand, are challenged on a regular basis because their position requires communication of values in a public space, against which the public can evaluate their actions. A delimitating definition therefore ties the question of integrity to people in leading positions. (shrink)

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.”.

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)

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)

We have benefited from conversations with Archon Fung, Brian Jacob, Todd Pittinsky, Peter Schuck, Ani Satz, Andrew Williams, and students in a joint class on statistics and ethics at the John F. Kennedy School of Government in October 2002. We are also grateful to our audience at the conference “The Priority of Practice,” organized by Jonathan Wolff at University College London in September 2003, and to Arthur Applbaum, Miriam Avins, Frances Kamm, Simon Keller, Frederick Schauer, Alan Wertheimer, and the Editors (...) of Phi- losophy & Public Affairs for insightful comments. We have benefited from prepublication reading of Schauer’s work on profiling, Profiles, Probabilities, and Stereotypes (Cambridge, Mass: Harvard University Press, 2003). We thank Avedis Koutoujian for research assistance. (shrink)

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

For its elliptical style, What is Philosophy? appears to be fragmentary and inscrutable, and its reception has been correspondingly contentious. Following an intimation by Gilles Deleuze himself, this article proposes that his final book, written in collaboration with Félix Guattari, contains a philosophy of nature. To address this proposition, the article begins by outlining the comprehensive system of nature set out in What is Philosophy?, defining it as an open system in motion that conjoins philosophy with the historical preconditions and (...) intersects it with science and art. The article then addresses the precise method whereby the philosopher as an individual subject, emerging from nature, can succeed in becoming creative – that is, in creating concepts to bring forth new events. Finally, the brain turns out to be the pivot between the system and this method. What is Philosophy? thus presents an account of the brain based on a theory of the three specific planes of philosophy, science and art, and uses it to expand upon the idea of assemblage for a philosophy of nature. (shrink)

Risse is concerned with humanity's common ownership of the earth, which has implications for a range of global problems. In particular, it helps illuminate the moral claims to international aid of small island nations whose existence is threatened by global climate change--such as Kiribati.

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)

The paper by Dupras and Bunnik is a useful addition to the literature on privacy in regards to datasets of human tissue/materials. In particular, the paper addresses import...

Philosophy emerged for the first time in ancient Greece and, according to Gilles Deleuze and Félix Guattari, it arose decisively with Plato through a triple transformation. Even today, the thought and creation of philosophy still require a triple transformation, despite the fact that the historical preconditions under which a philosopher pursues his or her task have changed since Greek antiquity. In this article, I introduce the concept of the triple transformation, which ensues from my examination of What is Philosophy?, the (...) last jointly authored book of Deleuze and Guattari. Therein they define philosophy as the activity that consists of creating concepts in order to bring forth new events... (shrink)

Are incorrect judgments on false belief tasks better explained within the framework of a conceptual change theory or a bias theory? Conceptual change theory posits a change in the form of reasoning from 3 to 4 years old while bias theory posits that processing factors are responsible for errors among younger children. The results from three experiments showed that children who failed a test of false belief took as long to respond as those who passed, and both groups of children (...) took longer to respond to belief questions than to questions about prior states of reality. These results seem to support the bias theory. (shrink)

This essay defends an account of the duties to the global poor that is informed by the empirical question of what makes countries rich or poor, and that tends to be broadly in agreement with John Rawlss account in The Law of Peoples. I begin by introducing the debate about the sources of growth and explore its implications for duties towards the poor. Next I explore whether (and deny that) there are any further-reaching duties towards the poor. Finally, I ask (...) about the moral foundations for the duties to the poor of the sort that earlier parts argue there are. (shrink)

This paper argues for a theory of memory that I have coined “the theory of causal memory processes”. The central claim of the paper is that it is more empirically sound to construct theories of memory in accordance with the theory of causal processes rather than in accordance with causality as regulation. In order to put this claim forward I will, first, describe what kind of function causality serves in philosophical theories of memory. Secondly, I will show that regularity theories (...) of causation is dominant in the causal theories of memory. Thirdly, I will account for the theory of causal processes. Lastly, I will sketch a definition of the theory of causal memory processes. (shrink)