Ribonucleotide reductase (RNR) catalyzes the rate limiting step in the production of deoxyribonucleotides needed for DNA synthesis. In addition to the well documented allosteric regulation, the synthesis of the enzyme is also tightly regulated at the level of transcription. mRNAs for both subunits are cell cycle regulated and inducible by DNA damage in all organisms examined, including E. coli, S. cerevisiae and H. sapiens. This DNA damage regulation is thought to provide a metabolic state that facilitates DNA replicational repair processes. (...) S. cerevisiae also encodes a second large subunit gene, RNR3, that is expressed only in the presence of DNA damage. Genetic analysis of the DNA damage response in S. cerevisiae has shown that RNR expression is under both positive and negative control. Among mutants constitutive for RNR expression are the general transcriptional repression genes, SSN6 and TUP1. Mutations in POL1 and POL3 also activate RNR expression, indicating that the DNA damage sensory network may respond directly to blocks in DNA synthesis. A protein kinase, Dun1, has been identified that controls inducibility of RNR1, RNR2 and RNR3 in response to DNA damage and replication blocks. This result suggests that the RNR genes in S. cerevisiae form a regulon that is coordinately regulated by protein phosphorylation in response to DNA damage. (shrink)

The tumor suppressor protein p53 is intimately involved in the cellular response to DNA damage, controlling cell cycle arrest, apoptosis and the transcriptional induction of DNA damage inducible genes. A transcriptional target of p53, Gadd45, was recently found to bind to PCNA, a component of DNA replication/repair complexes, thereby implicating Gadd45 in DNA metabolism(1). Using biochemical assays, a role for Gadd45 in excision repair in vitro has been demonstrated(1). Antisense experiments have also indicated an in vivo role for the GADD45 (...) gene in UV‐irradiation survival. These discoveries establish a link between p53 and DNA repair through Gadd45. (shrink)

1 Introducing Monsieur Foucault Stephen J. Ball Michel Foucault is an enigma, a massively influential intellectual who steadfastly refused to align himself ...

In 1937, just as Dobzhansky published the book that later generations would laud as the foundation of the modern synthesis, the American Naturnlist published a symposium on "supraspecific variation in nature and in classification." Alfred C. Kinsey, who later became one of America's most controversial intellectuals for his study of basic behaviors in another sort of WASP,1 led off the symposium with a summary of his extensive work on a family of gall wasps, the Cynipidae. In his article, Kinsey strongly (...) advocated the central theme of the developing synthesis: Evolution at all scales, particularly macroevolution, could be explained by the genetic mechanisms observed in laboratories and local populations. He first complained that some geneticists and naturalists were still impeding a synthesis with their insistence upon causal separation of levels: "Just as some of the geneticists have insisted that the laboratory genetics may explain the nature and origin of Mendelian races, but not of natural species, so others indicate that the qualities of higher categories must be explained on bases other than those involved in species" (1937, p. 208). He then defended the central postulate. (shrink)

Foucault, Power, and Education invites internationally renowned scholar Stephen J. Ball to reflect on the importance and influence of Foucault on his work in educational policy.

According to a natural view of instrumental normativity, if you ought to do φ, and doing ψ is a necessary means for you to do φ, then you ought to do ψ. In “Instrumental Normativity: In Defense of the Transmission Principle,” Benjamin Kiesewetter defends this principle against certain actualist-inspired counterexamples. In this article I argue that Kiesewetter’s defense of the transmission principle fails. His arguments rely on certain principles—Joint Satisfiability and Reason Transmission—which we should not accept in the unqualified forms (...) needed to establish his conclusion. (shrink)

Are predictions about how one will freely and intentionally behave in the future ever relevant to how one ought to behave? There is good reason to think they are. As imperfect agents, we have responsibilities of self-management, which seem to require that we take account of the predictable ways we're liable to go wrong. I defend this conclusion against certain objections to the effect that incorporating predictions concerning one's voluntary conduct into one's practical reasoning amounts to evading responsibility for that (...) conduct. There is, however, some truth to this sort of objection. To understand the legitimate role of self-prediction in practical reasoning, we need to distinguish instances of coping responsibly with an anticipated failure to behave as one ought, on the one hand, from mere acquiescence in one's flaws, on the other. I argue that, to draw this distinction, we must recognize certain limits on the use of self-prediction as a ground of choice. (shrink)

There is a wide-spread belief amongst theorists of mind and language. This is that in order to understand the relation between language, thought, and reality we need a theory of meaning and content, that is, a normative, formal science of meaning, which is an extension and theoretical deepening of folk ideas about meaning. This book argues that this is false, offering an alternative idea: The form of a theory that illuminates the relation of language, thought, and reality is a theory (...) of language agency. In a nutshell, the theory of language agency is a theory of competence, without being a theory of understanding or grasping rules. It is a theory of cognitive structure and language production. This theory distils all there is to say about language, thought, and reality. It does not supplement a theory of truth-conditions or semantic norms. It is not the explanation of how a speaker, qua cognitive system causally embedded in a larger reality, is able to use a language with some pre-existing semantic characterization. There is no pre-existing semantic characterization. Nevertheless, there are facts of meaning, as good as any other facts. The dissolution of the theory of meaning is accompanied by another disappearance. That is the disappearance of metaphysical questions in a number of domains. Once we complete the theory of language agency, then just as theoretical questions about meaning disappear, certain theoretical questions about existence disappear. Having provided a theory of the language agency for talk of meaning, fact, property, relation, and proposition, there is no question left over about what meanings, facts, properties, relations, and propositions are. There is no theory to be given of their natures. This is not because they have primitive irreducible natures. Rather it is because, in a sense to be clarified in this work, they lack natures. I call this approach to language agency Global Expressivism. That is because it generalizes some of the insights brought to the study of value-language by expressivists. However, it removes these insights from the clouding affects of attempting to make expressivism a semantic theory. Expressivism about value fails as a semantic theory of value talk. However, global expressivism can succeed as a theory of all talk because it is not a semantic theory but a theory of language agency, wherein the theory of meaning is replaced by a theory of talk about meaning. (shrink)

This article proposes 3 principles and 3 imperatives as the philosophical foundations of a global journalism ethics. The central claim is that the globalization of news media requires a radical rethinking of the principles and standards of journalism ethics, through the adoption of a cosmopolitan attitude. The article explains how and why ethicists should construct a global journalism ethics, using a contractualist approach. It then formulates 3 "claims" or principles: the claims of credibility, justifiable consequence, and humanity. The claim of (...) humanity is developed further by the formulation of 3 imperatives: to act as a global agent, to serve world citizens, and to enhance nonparochial understandings. The article concludes by considering some implications of a cosmopolitan attitude for the practice of journalism. (shrink)

The current system of ethical oversight in the United States is based on Institutional Review Board (IRB) review. The system was established in response to well-known and egregious mistreatment of subjects in both biomedical and social and behavioral research. In the decades since the research regulations were enacted, reaction to the burden of IRB oversight has led the system to focus on compliance and limit its active oversight disproportionately to studies that could present the risk of physical harm. At the (...) same time, the characteristics of the research enterprise have changed and methodologies now present novel risks that were not envisioned in the regulations. We convened a group of IRB professionals, academic leaders, and others to discuss limitations of the current system, how that system could be changed to recognize evolving risks and an increasing focus on participant and community voice, and how it could better serve the needs of researchers and support the societal project of science as a public good. Recommendations included a call to reexamine the academic incentive structure, to develop a system to support consideration of ethical principles from the time of study design, and to explicitly provide different ethical support and oversight for high-risk interventional trials and lower risk biomedical and social behavioral research. (shrink)

This essay responds to Hirstein, Sifferd and Fagan’s book, Responsible Brains, which claims that executive function is the guiding mechanism that supports both responsible agency and the necessity for some excuses. In contrast, I suggest that executive function is not the universal acid and the neuroscience at present contributes almost nothing to the necessary psychological level of explanation and analysis. To the extent neuroscience can be useful, it is virtually entirely dependent on well-validated psychology to correlate with the neuroscientific variables (...) under investigation. The essay considers what executive function is and what the neuroscience adds to our understanding of it. Then it addresses moral and legal responsibility generally, and specific doctrines. Executive function is seldom found to be the most perspicuous approach to any of the general or specific moral and legal questions. (shrink)

How, if at all, does one's intention to realize an end bear on the justification for taking the means to that end? Theories that allow that intending an end directly provides a reason to take the means are subject to a well-known "bootstrapping" objection. On the other hand, "anti-psychologistic" accounts—which seek to derive instrumental reasons directly from the reasons that support adopting the end itself—have unacceptable implications where an agent faces multiple rationally permissible options. An alternative, predictive, role for intention (...) in means-end reasoning is considered and rejected. A new proposal is then developed, according to which instrumental reasons are not merely reasons to perform an act necessary for a given end, but to perform the act for the sake of that end. (shrink)

War metaphors are ubiquitous in discussions of everything from political campaigns to battles with cancer to wars against crime, drugs, poverty, and even salad. Why are warfare metaphors so common, and what are the potential benefits and costs to using them to frame important social and political issues? We address these questions in a detailed case study by reviewing the empirical literature on the subject and by advancing our own theoretical account of the structure and function of war metaphors in (...) public discourse. We argue that war metaphors are omnipresent because they draw on basic and widely shared schematic knowledge that efficiently structures our ability to reason and communicate about many different types of situations, and they reliably express an urgent, negatively valenced emotional tone that captures attention and motivates action. Nevertheless, we find that the meaning of war metaphors is intimately tied to the context in which they are used, which may result in either positive or negative outcomes, depending on the situation. Thus, blanket statements about whether or not a war frame is useful are misguided or overly constraining. Here we situate our case study results in relation to popular theories of metaphoric representation and processing and offer some guidelines for using a war framing effectively. This work helps illuminate the complex, dynamic, and nuanced functions of metaphor in cognition in general, and in public discourse in particular. (shrink)

A comprehensive theory ofeven if needs to account for consequent ‘entailing’even ifs and in particular those of theif-focused variety. This is where the theory ofeven if ceases to be neutral between conditional theories. I have argued thatif-focusedeven ifs,especially if andonly if can only be accounted for through the suppositional theory ofif. Furthermore, a particular interpretation of this theory — the conditional assertion theory — is needed to account foronly if and a type of metalinguistic negation ofQ if P. We therefore (...) have evidence that the currently accepted approaches to conditionals are basically wrong about the semantic forms they attribute toif P, Q.11. (shrink)

Provides guiding principles and values for practising responsible global media ethics.

Recognizing that students are fundamentally engaged in a process of learning and self-development, ethical review of sub-doctoral student research should be proportionate to that objective. A student's tutor has the pedagogical role and an ethics committee should not interfere with that relationship other than to seek to avoid harms unforeseen by either the student or tutor. Underpowered or other statistically or methodologically flawed sub-doctoral research should not however, in general, be regarded as ethically concerning. With the proviso that no subject (...) is harmed the student can be allowed to learn such lessons as their mistakes may afford them. (shrink)

This paper discusses some problems with the field of educational studies and considers the role of post-structuralist theory in shifting the study of education away from a 'technical rationalist' approach towards an 'intellectual intelligence' stance that stresses contingency, disidentification and risk-taking.

According to the view Rik Peels defends in Responsible Belief, one is responsible for believing something only if that belief was the result of choices one made voluntarily, and for which one may be held responsible. Here, I argue against this voluntarist account of doxastic responsibility and in favor of the rationalist position that a person is responsible for her beliefs insofar as they are under the influence of her reason. In particular, I argue that the latter yields a more (...) plausible account of the conditions under which ignorance may serve as an excuse for wrongdoing. (shrink)

The publication of Michel Foucault’s lectures at the Collège de France in the late 1970s has provided new insight into crucial developments in his late work, including the return to an analysis of the state and the introduction of biopolitics as a central theme. According to one dominant interpretation, these shifts did not entail a fundamental methodological break; the approach Foucault developed in his work on knowledge/power was simply applied to new objects. The present article argues that this reading — (...) which is colored by the overwhelming privilege afforded to Discipline and Punish in secondary literature — obscures an important modification in Foucault’s method and diagnostic style that occurred between the introduction of biopolitics in 1976 (in Society Must Be Defended) and the lectures of 1978 ( Security, Territory, Population) and 1979 ( Birth of Biopolitics). Foucault’s initial analysis of biopolitics was couched in surprisingly epochal and totalizing claims about the characteristic forms of power in modernity. The later lectures, by contrast, suggest what I propose to call a ‘topological’ analysis that examines the ‘patterns of correlation’ in which heterogeneous elements — techniques, material forms, institutional structures and technologies of power — are configured, as well as the redeployments through which these patterns are transformed. I also indicate how attention to the topological dimension of Foucault’s analysis might change our understanding of key themes in his late work: biopolitics, the analysis of thinking, and the concept of governmentality. (shrink)

It is usually maintained by biologists and philosophers alike that essentialism is incompatible with evolutionary biology, and that abandoning essentialism was a precondition of progress being made in the biological sciences. These claims pose a problem for anyone familiar with both evolutionary biology and current metaphysics. Very few current scientific theories enjoy the prestige of evolutionary biology. But essentialism – long in the bad books amongst both biologists and philosophers – has been enjoying a strong resurgence of late amongst analytical (...) philosophers with a taste for metaphysics. Indeed, to impartial observers it is likely to appear that both evolutionary biology and essentialism are as well supported in their respective domains as could reasonably be expected. There is thus at least a prima facie tension here between evolutionary biology, metaphysics and, as we shall see, pre-theoretical common sense. (shrink)

People regularly encounter metaphors in a variety of different communicative settings, but most studies of metaphor framing have relied exclusively on written materials. Across three experiments (N...

Recently in these pages it has been argued that a relatively straightforward version of an old argument based on evolutionary biology and psychology can be employed to support the view that innate ideas are a naturalistic source of metaphysical knowledge. While sympathetic to the view that the “evolutionary argument” is pregnant with philosophical implications, I show in this paper how it needs to be developed and deployed in order to avoid serious philosophical difficulties and unnecessary complications. I sketch a revised (...) version of the evolutionary argument, place it in a new context, and show that this version in this context is not vulnerable to the standard criticisms levelled against arguments of this general type. The philosophical import of this version of the argument lies not in any metaphysical conclusions it sanctions directly, but in the support it lends to the metaphilosophy of commonsense. (shrink)

In this clearly written undergraduate textbook, Stephen Laumakis explains the origin and development of Buddhist ideas and concepts, focusing on the philosophical ideas and arguments presented and defended by selected thinkers and sutras from various traditions. He starts with a sketch of the Buddha and the Dharma, and highlights the origins of Buddhism in India. He then considers specific details of the Dharma with special attention to Buddhist metaphysics and epistemology, and examines the development of Buddhism in China, Japan, (...) and Tibet, concluding with the ideas of the Dalai Lama and Thich Nhat Hanh. In each chapter he includes explanations of key terms and teachings, excerpts from primary source materials, and presentations of the arguments for each position. His book will be an invaluable guide for all who are interested in this rich and vibrant philosophy. (shrink)

This chapter provide an introductory portrait of global media ethics as an evolving discipline in broad strokes—its motivating questions, its distinct concerns and methods, how the discipline is related to other forms of ethics, and why we need a global media ethics. Since our global world is linked by many forms of media, the chapter argues that we need an accompanying global media ethics that challenges the use of media to promote racism, xenophobia, extreme nationalism, and the denial of human (...) rights. The chapter explores the types of research and writing that comprise global media ethics and concludes with an outline of how a global media ethics can be realized in practice. (shrink)

We address a previous finding in the business ethics literature in which accounting professionals in higher rank levels, i.e., “manager” or “partner” of auditing firms, appear to have lower moral reasoning ability than their junior counterparts. Prior investigations have relied upon a similar methodology for estimating ethical beliefs, namely testing “moral reasoning ability” using either the Moral Judgment Interview or Defining Issues Test. In the present study, we use a multiple vignettes approach to test for the existence of the inverse (...) rank-ethical beliefs effect. With only 2 of the 30 vignettes resulting in both managers and partners being more accepting of the ethically charged behaviors, the results presented here using this alternative methodology are generally not supportive of the inverse rank-ethical beliefs phenomenon. We also use a multivariate analysis in order to control for demographic characteristics. Our results suggest that the most robust predictor of ethical attitudes among accounting practitioners is age, not rank within a firm. (shrink)

This article addresses the question of the relevance of brain imaging to legal criteria that are behavioral, that is, that require evaluation of a defendant's actions or mental states. It begins with the legal standard for the admissibility of scientific and technical evidence. Then it considers the relevance of imaging to behavioral legal criteria. The problem is translating mechanistic neuroscience data into the law's folk psychological standards. It uses examples from the criminal law, but the analysis generalizes to behavioral criteria (...) in the civil law. The central question is, “How, precisely, does the proffered scan or data based on scanning answer the specific legal question it supposedly helps answer?” I conclude that, at present, brain imaging has little relevance to behavioral legal criteria. The final section takes note of a rampant disorder, brain overclaim syndrome, and offers a remedy, cognitive jurotherapy. (shrink)

This book reports recent landmark developments and the state of the art in NDS science in psychological theory and research.

We survey students at two Southern United States universities (one public and one private, religiously affiliated). Using a survey instrument that includes 25 vignettes, we test two important hypotheses: whether ethical attitudes are affected by religiosity (H1) and whether ethical attitudes are affected by courses in ethics, religion or theology (H2). Using a definition of religiosity based on behavior (church attendance), our results indicate that religiosity is a statistically significant predictor of responses in a number of ethical scenarios. In seven (...) of the eight vignettes for which religiosity is significant, the effect is negative, implying that it reduces the acceptability of ethically-charged scenarios. Completion of ethics or religion classes, however, was a significant predictor of ethical attitudes in only two of the 25 vignettes (and in the expected direction). We also find that males and younger respondents appear to be more accepting of the ethically-questionable vignettes. We conclude that factors outside of the educational system may be more influential in shaping responses to ethical vignettes than are ethics and religion courses. (shrink)

John Laumakis has offered a thought-provoking, but ultimately unpersuasive argument in favor of playing to your opponent’s strength instead of playing to their weakness. In the course of this reply, we hope to show that the idea of PTS not only undermines the real goal of athletic competition, but it also rests upon a confusion between matters of morality and the aims of sports, as well as equivocations on the kind of ‘excellence’ one pursues, and the nature of the ‘challenge’ (...) involved in sport. We also plan to raise a serious objection against the logical consistency of PTS and note its incompatibility with real-world game smarts and tactics. Finally, we offer our own explanation for why ‘it is improbable that many coaches and athletes will shift their strategy from PTW to PTS.’. (shrink)

Maurice Merleau-Ponty’s ‘flesh of the world’ speaks to an embodied connection to the spaces we inhabit deeply, primally, elementally. Flesh suggests water and its circulations, air and its respirations, earth and its conformations, fire and its inspirations. Flesh speaks to our bodily relations with the elements of a more-than-human world. This paper explores the felt imperative to these relations where, as Merleau-Ponty put it, ‘all distance is traversed’ and wherein movement arises not specifically in the body, but in the nexus (...) and intertwining of bodily engagement with the world. There is a primacy to movement that registers in the living body in its carnal ties to the elements of the world’s flesh. The ‘radical reflection’ on the ‘flesh of the world’ to which this analysis aspires in turn bears upon the general field of gestural reciprocities and connections, providing the insight that intimate gestures of the flesh, such as the embrace, are primordial attunements, motions of rhythm and reciprocity, that emanate from the world in identification with it. The embrace is fundamentally, elementally, a gesture of landscape dwelling. A phenomenology of elemental motions provides the textual reminder that to be at home in various landscapes means to know what it is to be embraced corporeally, sensually, within the human and especially the more-than-human folds of the world. Indo-Pacific Journal of Phenomenology , Volume 6, Edition 1 May 2006. (shrink)