Histone deacetylase inhibitors (HDACi) are in clinical trials against a variety of cancers. Despite early successes, results against the more common solid tumors have been mixed. How is it that so many cancers, and most normal cells, tolerate the disruption caused by HDACi‐induced protein hyperacetylation? And why are a few cancers so sensitive? Here we discuss recent results showing that human cells mount a coordinated transcriptional response to HDACi that mitigates their toxic effects. We present a hypothetical signaling system that (...) could trigger and mediate this response. To account for the existence of such a response, we note that HDACi of various chemical types are made by a variety of organisms to kill or suppress competitors. We suggest that the resistance response in human cells is a necessary evolutionary consequence of exposure to environmental HDACi. We speculate that cancers sensitive to HDACi are those in which the resistance response has been compromised by mutation. Identifying such mutations will allow targeting of HDACi therapy to potentially susceptible cancers. (shrink)

Part I. Gnosticism and other religious movements of antiquity -- part II. Crossing boundaries : Gnosticism and Platonism.

Al-Maʾmūn, the Inquisition, and the Quest for Caliphal Authority. By John Abdallah Nawas. Resources in Arabic and Islamic Studies, vol. 4. Atlanta: Lockwood Press, 2015. Pp. xvi + 340. $45.

The 1981 book Genes, Mind and Culture by Edward O. Wilson and Charles J. Lumsden attempts to offer a comprehensive theory of the linkage between biological and cultural evolution. In the following 21 May 1982 radio broadcast, produced by Julian Brown under the auspices of the British Broadcasting Corporation, Wilson is joined by a philosopher, a geneticist, and a religion scholar in a discussion of “gene culture co‐evolution” and of other issues raised by sociobiology. The discussion is introduced and chaired (...) by the editor of Nature, John Maddox. (shrink)

In order to defend the regress argument for foundationalism against Post’s objection that relevant forms of inferential justification are not transitive, Lydia McGrew and Timothy McGrew define a relation E of positive evidence, which, they contend, has the following features: It is a necessary condition for any inferential justification; it is transitive and irreflexive; and it enables both a strengthened regress argument proof against Post’s objection and an argument that nothing can ever appear in its own justificational ancestry. In reply, (...) we construct in their own terms both a counterexample to the would-be transitivity of E, and a related objection to their never-in-its-own-ancestry argument. We also rebut their rejection of certain counterexamples to the would-be transitivity of some forms of inferential justification. By doing so, and by questioning their transitivity claim for E, we aim to further the project of undermining the circularity arguments advanced by a zoo of skeptics, relativists, antirealists and internalists against realism and externalism. (shrink)

John Post has argued that the traditional regress argument against nonfoundational justificatory structures does not go through because it depends on the false assumption that “justifies” is in general transitive. But, says Post, many significant justificatory relations are not transitive. The authors counter that there is an evidential relation essential to all inferential justification, regardless of specific inference form or degree of carried-over justificatory force, which is in general transitive. They respond to attempted counterexamples to transitivity brought by Watkins (...) and Salmon as well as to Post’s, arguing that none of these counterexamples apply to the relation they are describing. Given the revived transitivity assumption using this relation, the regress argument does indeed demonstrate the need for foundational stopping points in inferential justification. (shrink)

The Occupy Wall Street movement of 2011 and its corollaries, Occupy Sandy and Occupy Debt, have been largely understood as secular movements. In spite of this, religious actors not only participated, but in some cases played an integral role within the movement, lending material support, organizing expertise, and public statements of support. We rely on interviews with faith leaders in New York and Oakland, and engage in an analysis of print and online media to explore the role of religious actors (...) and groups in Occupy Wall Street. Religious participants were often long-time veterans of progressive political struggles and drew inspiration from their faith traditions. Nonetheless, religious commitments were secondary to political objectives shared by themselves and their secular counterparts. Religious leaders believed they offered symbolic authority to the movement and highlighted this in their engagement in the hope of giving it greater moral weight. Current discussions on postsecularism and public religions are considered. (shrink)

Introduction: ethical exigency -- Influence and escape -- Positioning -- Upon transcendence -- Ethical optics -- From stranger to neighbor -- This strange mission -- Waging peace -- Conclusion: the least of these.

The fusion of law and equity in common law systems was a crucial moment in the development of the modern law. In this volume leading scholars assess the significance of the fusion of law and equity from comparative, doctrinal, historical and theoretical perspectives.

The article reviews several books about philosophical isuuses including "Against Coherence: Truth, Probability, and Justification," by Olsson Erik J., "Fixing Frege," by Burgess John, "Events and Semantic Architecture," by Pietroski Paul M.

In modern evolutionary theory, selection acts on particular genes and assemblages of genes that operate through phenotypes expressed in environments. This view, however, overlooks the fact that organisms often alter their environments in pursuit of fitness needs and thus modify some environmental selection pressures. Niche construction theory introduces a reciprocal causal process that modifies natural selection relative to three general kinds of environmental components: abiota, biota (other organisms), and artifacts. The ways in which niche-constructing organisms can construct or modify the (...) components differ. Modification of abiota, for example, may have different consequences from the construction of artifacts. Some changes in abiota may simply be caused by the by-products of metabolisms and activities of organisms. Alternatively, artifacts may be “extended phenotypes” that demonstrate obvious prior “design” and “construction” by organisms in the service of fitness needs. Nevertheless, adaptation should always account for the reciprocity between constructed niches and the living agents that construct them. Looking to well-adapted nature for inspiration for human-built artifacts must account for this reciprocity between phenotype and constructed environment as well as the novel features of human architecture, including frank intentionality of design and novel culturally acquired knowledge. (shrink)

In his book on Nietzsche, Gilles Deleuze puts forth an idiosyncratic interpretation of the eternal return: “However far they go, however deep the becoming-reactive of forces, reactive forces will not return. The small, petty, reactive man will not return.”1 The idea of eternal return is particularly suited to James Joyce’s Ulysses. This is because Joyce’s book concerns the return of the hero Ulysses in the person of Leopold Bloom. One way that the hero wanders is by incarnating as the unlikely (...) Bloom. What is to be the nature of Bloom’s relation to Ulysses? Joyce’s vision of an interpenetration of present and past corresponds to the terms Deleuze lays down. There is to be a return but not verbatim. Thus, Joyce .. (shrink)

This book explores the intimate connections, conflicts and discontinuities between religion and philosophy in the Platonic and Neoplatonic traditions from Antiquity to the early Medieval period. It presents a broader comparative view of Platonism by examining the strong Platonist resonances among different philosophical/religious traditions, primarily Jewish, Christian, Islamic and Hindu, and suggests many new ways of thinking about the relation between these two fields or disciplines that have in modern times become such distinct and, at times, entirely separate domains.

Collapse is a term that has attracted much attention in social science literature in recent years, but there remain substantial areas of disagreement about how it should be understood in historical contexts. More specifically, the use of the term collapse often merely serves to dramatize long-past events, to push human actors into the background, and to mystify the past intellectually. At the same time, since human societies are complex systems, the alternative involves grasping the challenges that a holistic analysis presents, (...) taking account of the many different levels and paces at which societies function, and developing appropriate methods that help to integrate science and history. Often neglected elements in considerations of collapse are the perceptions and beliefs of a historical society and how a given society deals with change; an important facet of this, almost entirely ignored in the discussion, is the understanding of time held by the individuals and social groups affected by change; and from this perspective ‘collapse’ depends very much on perception, including the perceptions of the modern commentator. With this in mind, this article challenges simplistic notions of ‘collapse’ in an effort to encourage a more nuanced understanding of the impact and process of both social and environmental change on past human societies. (shrink)

v. 1. From Plato and the old academy to middle platonism -- v. 2. Middle platonic and gnostic texts.

This book examines six plays by Shakespeare (Love's Labour's Lost, Hamlet, As You Like It, Twelfth Night, The Winter's Tale, and The Tempest) as dramatizations of the Renaissance court in its developing history - a history searched by Shakespeare to disclose its most characteristic gains and losses. For these plays do not simply celebrate Tudor and Stuart rule: they scrutinize it too, in the centre of its institutional theatre of power, the court. This book shows how, if the plays came (...) into the court, the court also came into the plays, with its most salient features - its competitiveness, its inner tensions and its contradictions, its language, its cultural life and its entertainments - exposed to the scrutiny of an art-form that proved itself to be a new mode of historical understanding. (shrink)

Sustainability and sustainable development have become key phrases of the politics of the environment. They are at the centre of much environmental discourse and indeed of the series of which this collection is a part. This volume brings together a number of recent papers that address the ethical and political assumptions that underlie different uses of those concepts.

This article examines a post-war generation of academics in the United States and in Britain, who, coming from lower-class families without any previous experience of university education, became internationally famous but nevertheless continued to feel out of place in the academic world. Pierre Bourdieu’s framework of habitus, field and doxa is useful in studying the world of such outsiders and exiles who shaped post-war sociology. Without an established canon of sociology, these students typically developed critical and creative perspectives on society. (...) In Britain the post-war welfare state was the foundation of this new breed of academics. John O’Neill is the classic example. In America ‘The Disobedient Generation’ were influenced by race, the Vietnam War, and the draft. William Connolly and Stephen Turner provide two case studies of highly successful academics who were often subjectively outsiders. ‘Event’ and ‘hazard’ imply that successful careers are in fact merely accidental. Neoliberalism may have closed off such accidental careers. (shrink)

A comprehensive draft overview of John Stuart Mill's public life and philosophy, including discussion of: 1. A System of Logic. – 2. The Greatest Happiness Principle. – 3. Progress, Liberty, and Democracy. – 4. Equality. – 5. India and Empire. – 6. Distribution, Socialism, and Sustainability.

By questioning the modern categories of Plato and Platonism, this book offers new ways of reading the Platonic dialogues and the many traditions that resonate ...