Promyelocytic leukaemia nuclear bodies (PML NBs) are generally present in all mammalian cells, and their integrity correlates with normal differentiation of promyelocytes. Mice that lack PML NBs have impaired immune function, exhibit chromosome instability and are sensitive to carcinogens. Although their direct role in nuclear activity is unclear, PML NBs are implicated in the regulation of transcription, apoptosis, tumour suppression and the anti‐viral response. An emerging view is that they represent sites where multi‐subunit complexes form and where post‐translational modification of (...) regulatory factors, such as p53, occurs in response to cellular stress. Following DNA damage, several repair factors transit through PML NBs in a temporally regulated manner implicating these bodies in DNA repair. We propose that PML NBs are dynamic sensors of cellular stress, which rapidly disassemble following DNA damage into large supramolecular complexes, dispersing associated repair factors to sites of damage. The dramatically increased total surface area available would enhance interactions between PML‐associated factors regulating DNA repair and apoptosis. BioEssays 26:963–977, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

It has recently been shown that stem and progenitor cells undergo population self‐renewal to maintain epithelial homeostasis. The fate of individual cells is stochastic but the production of proliferating and differentiating cells is balanced across the population. This new paradigm, originating in mouse epidermis and since extended to mouse oesophagus and mouse and Drosophila intestine, is in contrast to the long held model of epithelial maintenance by exclusively asymmetric division of stem cells. Recent lineage tracing studies have now shown that (...) wound responses vary between tissues, and that a stem cell reserve is not essential as cycling progenitors and even differentiating cells contribute to regeneration. (shrink)

PurposeTo evaluate the relationship between intraocular straylight perception and: (i) contrast sensitivity (CS), (ii) halo size, and (iii) hazard recognition distance, in the presence and absence of glare.Subjects and methodsParticipants were 15 (5 female) ophthalmologically healthy adults, aged 54.6–80.6 (median: 67.2) years. Intraocular straylight (log s) was measured using a straylight meter (C-Quant; Oculus GmbH, Wetzlar, Germany). CS with glare was measured clinically using the Optovist I device (Vistec Inc., Olching, Germany) and also within a driving simulator using Landolt Cs. (...) These were presented under both static or dynamic viewing conditions, and either with or without glare. Hazard detection distance was measured for simulated obstacles of varying contrast. For this, the participant was required to maintain a speed of 60 km/h within a custom-built nighttime driving simulator. Glare was simulated by LED arrays, moved by cable robots to mimic an oncoming car’s headlights. Halo size (“halometry”) was measured by moving Landolt Cs outward originating from the center of a static glare source. The outcome measure from “halometry” was the radius of the halo (angular extent, in degrees visual angle).ResultsThe correlation between intraocular straylight perception, log s, and hazard recognition distance under glare was poor for the low contrast obstacles (leading/subdominant eye: r = 0.27/r = 0.34). Conversely, log CS measured with glare strongly predicted hazard recognition distances under glare. This was true both when log CS was measured using a clinical device (Optovist I: r = 0.93) and within the driving simulator, under static (r = 0.69) and dynamic (r = 0.61) conditions, and also with “halometry” (r = 0.70). Glare reduced log CS and hazard recognition distance for almost all visual function parameters.ConclusionIntraocular straylight was a poor predictor of visual function and driving performance within this experiment. Conversely, CS was a strong predictor of both hazard recognition and halo extent. The presence of glare and motion lead to a degradation of CS in a driving simulator. Future studies are necessary to evaluate the effectiveness of all above-mentioned vision-related parameters for predicting fitness to drive under real-life conditions. (shrink)

This is a biography of the works of Richard Price, 1723-1791, one of the leading radical intellectuals of the late-18th century. By profession a dissenting minister, he was also a mathematician, a political pamphleteer, particularly on the American and French Revolutions, and a moral philosopher.

This is the first book to offer the best essays, articles, and speeches on ethics and intelligence that demonstrate the complex moral dilemmas in intelligence collection, analysis, and operations. Some are recently declassified and never before published, and all are written by authors whose backgrounds are as varied as their insights, including Robert M. Gates, former Director of the Central Intelligence Agency; John P. Langan, the Joseph Cardinal Bernardin Professor of Catholic Social Thought at the Kennedy Institute of Ethics, Georgetown (...) University; and Loch K. Johnson, Regents Professor of Political Science at the University of Georgia and recipient of the Owens Award for contributions to the understanding of U.S. intelligence activities. Creating the foundation for the study of ethics and intelligence by filling in the gap between warfare and philosophy, this is a valuable collection of literature for building an ethical code that is not dependent on any specific agency, department, or country. (shrink)

ABSTRACT:A wide range of research uses patterns of genetic variation to infer genetic similarity between individuals, typically referred to as genetic ancestry. This research includes inference of human demographic history, understanding the genetic architecture of traits, and predicting disease risk. Researchers are not just structuring an intellectual inquiry when using genetic ancestry, they are also creating analytical frameworks with broader societal ramifications. This essay presents an ethics framework in the spirit of virtue ethics for these researchers: rather than focus on (...) rule following, the framework is designed to build researchers’ capacities to react to the ethical dimensions of their work. The authors identify one overarching principle of intellectual freedom and responsibility, noting that freedom in all its guises comes with responsibility, and they identify and define four principles that collectively uphold researchers’ intellectual responsibility: truthfulness, justice and fairness, anti-racism, and public beneficence. Researchers should bring their practices into alignment with these principles, and to aid this, the authors name three common ways research practices infringe these principles, suggest a step-by-step process for aligning research choices with the principles, provide rules of thumb for achieving alignment, and give a worked case. The essay concludes by identifying support needed by researchers to act in accord with the proposed framework. (shrink)

At the time of writing, a British Member of Parliament has just been suspended from his Party for posting a Tweet in which he compared the level of serious adverse events after vaccination for COVI...

Slippery slope arguments have been important in the euthanasia debate for at least half a century. In 1957 the Cambridge legal scholar Glanville Williams wrote a controversial book, The Sanctity of Life and the Criminal Law, in which he presented the decriminalizing of euthanasia as a modern liberal proposal taking its rightful place alongside proposals to decriminalize contraception, sterilization, abortion, and attempted suicide (all of which the book also advocated).1 Opposition to these reforms was in turn presented as exclusively religious (...) and particularly Roman Catholic. Thus Williams asserted that "euthanasia can be condemned only according to religious opinion" (1957, p. 312).The following year, in .. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Reviewed by:Intimacy or Integrity: Philosophy and Cultural DifferenceDavid Jones and John A. SweeneyIntimacy or Integrity: Philosophy and Cultural Difference. By Thomas P. Kasulis. Honolulu: University of Hawai'i Press, 2002. Pp. xii + 183. Paper $14.95.Back in the early days of cross-cultural inquiry, scholars gained some territory in the understanding of cultural difference by focusing their attention on the distinction between the individualistic and the collective. Asians, especially East (...) Asians, were seen as motivated by collectivism, whereas Westerners were firmly rooted in individuality. This distinction afforded some comprehension of cultural difference and served a limited purpose in those early days of trying to understand Asia as a whole and the vast reach of difference among various Asian groups. However, we quickly outgrew our dependence on this distinction, although we continued to insist on making use of it. Thomas Kasulis offers us a new heuristic in his recent book Intimacy or Integrity: Philosophy and Cultural Difference, which is based on his 1998 Gilbert Ryle Lectures at Trent University.The book begins with a series of anecdotes, which is most fitting for what the author has in mind. These seemingly simple stories of cultural misunderstanding actually point to profound differences between Asian and Western cultural perspectives. Kasulis, however, rightly extends the boundaries of his discussion to traverse not only Asian/Western differences but also variations between cultures and subcultures as well. The thesis of the book addresses the too simplistic notion that Asians are simply more collectivist than their Western counterparts, and this thesis applies as well to differences within the structure of any culture's grand narrative. Put directly, the thesis is that there are recursive cultural patterns that orient themselves in two basic ways: "intimacy" and "integrity." These patterns reiterate themselves into complex theoretical manifestations through understandings of fact/value, what is and what should be (p. 11).Aware that he might easily fall into the old trap of a simplistic differentiating between "them and us," Kasulis is quick to point out that "it is unlikely that any culture is ever a perfect example of either an intimacy-dominant or integrity-dominant culture" (p. 11). In other words, "intimacy" and "integrity" (unlike collectivism and individualism) are both positive terms that continually, and recursively, foreground and background themselves in any given culture. For example, Americans, with their penchant for individuality and the benefits arising from it, such as the notion of rights, also value and understand intimacy as a feeling that is primary to one's being either a member of a family, a member of a group, or a citizen of a country. And to think that individuality has no value whatsoever in Asia or that there are no "individuals" in Asia is just being simpleminded. These two different ways of relating—intimacy and integrity—are explored in connection to the key relations of self/world, self/other, knower/known, thing/thing, and so forth (p. 13) throughout the book, as reflected in the chapter titles: "Cultural Orientations," "What Is Intimacy?" "What [End Page 603] Is Integrity?" "Intimacy and Integrity as Worldviews: Epistemology, Analysis and Argument, and Metaphysics," "The Normative Dimensions of Intimacy and Integrity: Aesthetics, Ethics, and Politics," and "Intercultural Conflict: When Intimacy and Integrity Collide."An important concern of this book, and an issue that is often overlooked by philosophers, is that philosophy is both a product and a producer of culture. If culture even becomes a matter of philosophical discussion, it is often cast in terms of a "philosophy of culture," that is, a part of our understanding of the role that culture plays in the more universal context of human existence (p. 13). Kasulis reminds us, however, of another (and perhaps more important) dimension of the study of what he calls "cultural philosophy," and that is that "philosophy itself is a cultural enterprise" (p. 14). By viewing philosophy in this way philosophers are able to check their tendency to believe erroneously that philosophy is a discipline that can achieve an understanding of, or even attempt to search for, universal, eternal, and transcultural truths. Kasulis points out that this too is a "tendency... related to cultural conditions" (p. 14); hence, "philosophy and... (shrink)

BackgroundThe ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines are widely endorsed but compliance is limited. We sought to determine whether journal-requested completion of an ARRIVE checklist improves full compliance with the guidelines.MethodsIn a randomised controlled trial, manuscripts reporting in vivo animal research submitted to PLOS ONE (March–June 2015) were randomly allocated to either requested completion of an ARRIVE checklist or current standard practice. Authors, academic editors, and peer reviewers were blinded to group allocation. Trained reviewers performed outcome adjudication (...) in duplicate by assessing manuscripts against an operationalised version of the ARRIVE guidelines that consists 108 items. Our primary outcome was the between-group differences in the proportion of manuscripts meeting all ARRIVE guideline checklist subitems.ResultsWe randomised 1689 manuscripts (control: n = 844, intervention: n = 845), of which 1269 were sent for peer review and 762 (control: n = 340; intervention: n = 332) accepted for publication. No manuscript in either group achieved full compliance with the ARRIVE checklist. Details of animal husbandry (ARRIVE subitem 9b) was the only subitem to show improvements in reporting, with the proportion of compliant manuscripts rising from 52.1 to 74.1% (X2 = 34.0, df = 1, p = 2.1 × 10−7) in the control and intervention groups, respectively.ConclusionsThese results suggest that altering the editorial process to include requests for a completed ARRIVE checklist is not enough to improve compliance with the ARRIVE guidelines. Other approaches, such as more stringent editorial policies or a targeted approach on key quality items, may promote improvements in reporting. (shrink)

Machine generated contents note: -- Preface -- Acknowledgements -- Notes on Contributors -- PART I: COMPLEXITY IN ANIMAL MINDS -- Introduction: M.McGonigle-Chalmers -- Relational and Absolute Discrimination Learning by Squirrel Monkeys: Establishing a Common Ground with Human Cognition; B.T.Jones -- Serial List Retention by Non-Human Primates: Complexity and Cognitive Continuity; F.R.Treichler -- The Use of Spatial Structure in Working Memory: A Comparative Standpoint; C.De Lillo -- The Emergence of Linear Sequencing in Children: A Continuity Account and a Formal Model; (...) M.McGonigle-Chalmers&I.Kusel -- Sensitivity to Quantity: What Counts Across Species?; S.T.Boysen&A.M.Yocom -- PART II: COMPLEXITY IN ROBOTS -- Editorial Introduction; D.McFarland -- Towards Cognitive Robotics: Robotics, Biology and Developmental Psychology; M.Lee, U.Nehmzow&M.Rodriguez -- Structuring Intelligence: The Role of Hierarchy, Modularity and Learning in Generating Intelligent Behaviour; J.J.Bryson -- Epistemology, Access, and Computational Models; G.Luger -- Reasoning About Representations in Autonomous Systems: What P´Olya and Lakatos Have To Say; A.Bundy -- PART III: LANGUAGE, EVOLUTION AND THE COMPLEX MIND -- Editorial Introduction; K.Stenning -- How to Qualify for a Cognitive Upgrade: Executive Control, Glass Ceilings, and the Limits of Simian Success; A.Clark -- Private Codes and Public Structures; C.Allen -- The Emergence of Complex Language; W.Hinzen -- Language Evolution: Enlarging the Picture; K.Stenning&M.Van Lambalgen -- Epilogue: Reminiscences of Brendan McGonigle -- Index. (shrink)

Keith Thomas: Gerald Edward Aylmer, 1926-2000 Adrian Hollis: William Spencer Barrett, 1914-2001 Bruce Williams: Charles Frederick Carter, 1919-2002 Malcolm Mackintosh: John Erickson, 1929-2002 J. H .R. Davis: Raymond William Firth, 1901-2002 F. M. L. Thompson: Hrothgar John Habakkuk, 1915-2002 A. W. Price: Richard Mervyn Hare, 1919-2002 Hugh Lloyd-Jones: Geoffrey Stephen Kirk, 1921-2003 Michael Lapidge and Peter Matthews: Vivien Anne Law, 1954-2002 Ann Moss: John Lough, 1913-2000 Terence Cave: Ian Dalrymple McFarlane, 1915-2002 Ludwig Paul: David Neil MacKenzie, 1926-2001 Peter (...) Birks: John Kieran Barry Moylan Nicholas, 1919-2002 Jonathan Shepard: Dimitri Dimitrievich Obolensky, 1918-2001 David Cannadine: John Harold Plumb, 1911-2001 Daniel Waley: Nicolai Rubinstein, 1911-2002 Ian Wood: John Michael Wallace-Hadrill, 1916-1985 R. G. M. Nisbet: William Smith Watt, 1913-2002 G. W. Bernard: Richard Bruce Wernham, 1906-1999. (shrink)

From a pre-publication review by the late Austrian economist, Don Lavoie, of George Mason University: -/- "The book's radical re-interpretation of property and contract is, I think, among the most powerful critiques of mainstream economics ever developed. It undermines the neoclassical way of thinking about property by articulating a theory of inalienable rights, and constructs out of this perspective a "labor theory of property" which is as different from Marx's labor theory of value as it is from neoclassicism. It traces (...) roots of such ideas in some fascinating and largely forgotten strands of the history of economics. It draws attention to the question of "responsibility" which neoclassicism has utterly lost sight of. It is startlingly fresh in its overall approach, and unusually well written in its presentation. ... It constitutes a better case for its economic democracy viewpoint than anything else in the literature." . (shrink)

Is morality rational? In this book Gauthier argues that moral principles are principles of rational choice. He proposes a principle whereby choice is made on an agreed basis of cooperation, rather than according to what would give an individual the greatest expectation of value. He shows that such a principle not only ensures mutual benefit and fairness, thus satisfying the standards of morality, but also that each person may actually expect greater utility by adhering to morality, even though the choice (...) did not have that end primarily in view. In resolving what may appear to be a paradox, the author establishes morals on the firm foundation of reason. Gauthier's argument includes an account of value, linking it to preference and utility; a discussion of the curcumstances in which morality is unnecessary; and an application of morals by agreement to relations between peoples at different levels of development and different generations. Finally, he reflects on the assumptions about individuality and community made by his account of rationality and morality. (shrink)

I THE NATURE OF MAN To understand morals and politics, understand man. Leviathan , 'that mortal god, to which we owe under the immortal God, our peace and ...

Dramatic changes or revolutions in a field of science are often made by outsiders or 'trespassers,' who are not limited by the established, 'expert' approaches. Each essay in this diverse collection shows the fruits of intellectual trespassing and poaching among fields such as economics, Kantian ethics, Platonic philosophy, category theory, double-entry accounting, arbitrage, algebraic logic, series-parallel duality, and financial arithmetic.

The Logic of Leviathan The Moral and Political Theory of Thomas Hobbes.

Instead of the half-century old foundational feud between set theory and category theory, this paper argues that they are theories about two different complementary types of universals. The set-theoretic antinomies forced naïve set theory to be reformulated using some iterative notion of a set so that a set would always have higher type or rank than its members. Then the universal u_{F}={x|F(x)} for a property F() could never be self-predicative in the sense of u_{F}∈u_{F}. But the mathematical theory of categories, (...) dating from the mid-twentieth century, includes a theory of always-self-predicative universals--which can be seen as forming the "other bookend" to the never-self-predicative universals of set theory. The self-predicative universals of category theory show that the problem in the antinomies was not self-predication per se, but negated self-predication. They also provide a model (in the Platonic Heaven of mathematics) for the self-predicative strand of Plato's Theory of Forms as well as for the idea of a "concrete universal" in Hegel and similar ideas of paradigmatic exemplars in ordinary thought. (shrink)

The Sociosexual Orientation Inventory (SOI; Simpson & Gangestad 1991) is a self-report measure of individual differences in human mating strategies. Low SOI scores signify that a person is sociosexually restricted, or follows a more monogamous mating strategy. High SOI scores indicate that an individual is unrestricted, or has a more promiscuous mating strategy. As part of the International Sexuality Description Project (ISDP), the SOI was translated from English into 25 additional languages and administered to a total sample of 14,059 people (...) across 48 nations. Responses to the SOI were used to address four main issues. First, the psychometric properties of the SOI were examined in cross-cultural perspective. The SOI possessed adequate reliability and validity both within and across a diverse range of modern cultures. Second, theories concerning the systematic distribution of sociosexuality across cultures were evaluated. Both operational sex ratios and reproductively demanding environments related in evolutionary-predicted ways to national levels of sociosexuality. Third, sex differences in sociosexuality were generally large and demonstrated cross-cultural universality across the 48 nations of the ISDP, confirming several evolutionary theories of human mating. Fourth, sex differences in sociosexuality were significantly larger when reproductive environments were demanding but were reduced to more moderate levels in cultures with more political and economic gender equality. Implications for evolutionary and social role theories of human sexuality are discussed. Key Words: culture; gender; mating; reproduction; sex differences; sex roles; sexual strategies; sociosexuality. (shrink)

Here a group of philosophers, economists and political theorists discuss the work of David Gauthier, which seeks to show that rational individuals would accept certain moral constraints on their choices. The possibilities and limitations of a contractarian approach to issues of justice is analyzed.

The principle of alternate possibilities (PAP), making the ability to do otherwise a necessary condition for moral responsibility, is supposed by Harry Frankfurt, John Fischer, and others to succumb to a peculiar kind of counterexample. The paper reviews the main problems with the counterexample that have surfaced over the years, and shows how most can be addressed within the terms of the current debate. But one problem seems ineliminable: because Frankfurt''s example relies on a counterfactual intervener to preclude alternatives to (...) the person''s action, it is not possible for it to preclude all alternatives (intervention that is contingent upon a trigger cannot bring it about that the trigger never occurred). This makes it possible for the determined PAPist to maintain that some pre-intervention deviation is always available to ground moral responsibility. In reply, the critic of PAP can examine all the candidate deviations and argue their irrelevance to moral responsibility (a daunting prospect); or the critic can dispense with counterfactual intervention altogether. The paper pursues the second of these strategies, developing three examples of noncounterfactual intervention in which (i) the agent has no alternatives (and a fortiori no morally relevant alternatives), yet (ii) there is just as much reason to think that the agent is morally responsible as there was in Frankfurt''s original example. The new counterexamples do suffer from one liability, but this is insufficient in the end to repair PAP''s conceptual connection between moral responsibility and alternate possibilities. (shrink)

Spirituality and storytelling can be resources in aging successfully and in dying well given the constraints of modern day Western culture. This paper explores the relationship of aging to time and the dynamic process of the life course and discusses issues related to confronting mortality, including suffering, finitude, spirituality, and spiritual closure in regard to death. And, finally, the role of narrative in this process is taken up.

The use of remember–know judgments to assess subjective experience associated with memory retrieval, or as measures of recollection and familiarity processes, has been controversial. In the current study we had participants think aloud during study and provide verbal reports at test for remember–know and confidence judgments. Results indicated that the vast majority of remember judgments for studied items were associated with recollection from study , but this correspondence was less likely for high-confidence judgments . Instead, high-confidence judgments were more likely (...) than remember judgments to be associated with incorrect recollection and a lack of recollection. Know judgments were typically associated with a lack of recollection , but still included recollection from the study context . Thus, although remember judgments provided fairly accurate assessments of retrieval including contextual details, know judgments did not provide accurate assessments of retrieval lacking contextual details. (shrink)

A science sutra -- Non-self (Anatman) -- Impermanence (Anitya) -- Connectedness (Pratitya-Samutpada) -- Engagement, part 1 (Dukkha) -- Engagement, part 2 (Karma) -- Meaning (existential Biobuddhism?).

Through a series of essays, the author discusses the conflict between cultural and biological evolution, covering intelligent design, gender differences, and the meaning of life while offering insight into the ethical aspects of civilization.

War has broken out in the technological global economy, principally in battles over intellectual property. A particularly fierce aspect ofthis battle sets people who guard proprietary software against hackers, who want information to be free. The key challenge today is to produce an adequate conceptual lens for seeing what ethically is at stake in this battle. Toward this end, this paper uses the just war tradition to analyze differences between proponents of Free Software and proponents of Open Source Software. This (...) paper’s use of three just war criteria—Just Cause, Right Intention, and Discrimination—illustrates how the just war tradition can raise the level of ethical awareness about the intellectual property wars that continue to rage in the technological global economy. (shrink)

War has broken out in the technological global economy, principally in battles over intellectual property. A particularly fierce aspect ofthis battle sets people who guard proprietary software against hackers, who want information to be free. The key challenge today is to produce an adequate conceptual lens for seeing what ethically is at stake in this battle. Toward this end, this paper uses the just war tradition to analyze differences between proponents of Free Software and proponents of Open Source Software. This (...) paper’s use of three just war criteria—Just Cause, Right Intention, and Discrimination—illustrates how the just war tradition can raise the level of ethical awareness about the intellectual property wars that continue to rage in the technological global economy. (shrink)