Horizontal gene transfer in the form of long DNA fragments has changed our view of bacterial evolution. Recently, we discovered that such processes may also occur with the massive amounts of short and damaged DNA in the environment, and even with truly ancient DNA. Although it presently remains unclear how often it takes place in nature, horizontal gene transfer of short and damaged DNA opens up the possibility for genetic exchange across distinct species in both time and space. (...) In this essay, we speculate on the potential evolutionary consequences of this phenomenon. We argue that it may challenge basic assumptions in evolutionary theory; that it may have distant origins in life's history; and that horizontal gene transfer should be viewed as an evolutionary strategy not only preceding but causally underpinning the evolution of sexual reproduction. (shrink)

RNA polymerase II is recruited to DNA double‐strand breaks (DSBs), transcribes the sequences that flank the break and produces a novel RNA type that has been termed damage‐induced long non‐coding RNA (dilncRNA). DilncRNAs can be processed into short, miRNA‐like molecules or degraded by different ribonucleases. They can also form double‐stranded RNAs or DNA:RNA hybrids. The DNA:RNA hybrids formed at DSBs contribute to the recruitment of repair factors during the early steps of homologous recombination (HR) and, in this way, (...) contribute to the accuracy of the DNA repair. However, if not resolved, the DNA:RNA hybrids are highly mutagenic and prevent the recruitment of later HR factors. Here recent discoveries about the synthesis, processing, and degradation of dilncRNAs are revised. The focus is on RNA clearance, a necessary step for the successful repair of DSBs and the aim is to reconcile contradictory findings on the effects of dilncRNAs and DNA:RNA hybrids in HR. (shrink)

It is of fundamental importance to understand how the individual processes of gene expression, transcription, and translation, as well as mRNA and protein stability, act in concert to produce dynamic cellular proteomes. We use the concept of response times to illustrate the relation between degradation processes and responsiveness of the proteome to system changes and to provide supporting experimental evidence: proteins with short response times tend to be more strongly up‐regulated after 1 hour of TNFα stimulation than proteins with (...) longer response times. Furthermore, based on process‐dependent response times, we demonstrate that synthesis and degradation act in concert to enable rapid responses. Finally, by building on a previously published data set quantifying the mammalian gene expression cascade, we speculate on how combinations of stable and unstable mRNAs and proteins may be wired to transcriptional or translational regulation to support gene function. (shrink)

Fred Sanger, the inventor of the first protein, RNA and DNA sequencing methods, has traditionally been seen as a technical scientist, engaged in laboratory bench work and not interested at all in intellectual debates in biology. In his autobiography and commentaries by fellow researchers, he is portrayed as having a trajectory exclusively dependent on technological progress. The scarce historical scholarship on Sanger partially challenges these accounts by highlighting the importance of professional contacts, institutional and disciplinary moves in his career, spanning (...) from 1940 to 1983. This paper will complement such literature by focusing, for the first time, on the transition of Sanger’s sequencing strategies from degrading to copying the target molecule, which occurred in the late 1960s as he was shifting from protein and RNA to DNA sequencing, shortly after his move from the Department of Biochemistry to the Laboratory of Molecular Biology, both based in Cambridge (UK). Through a reinterpretation of Sanger’s papers and retrospective accounts and a pioneering investigation of his laboratory notebooks, I will claim that sequencing shifted from the working procedures of organic chemistry to those of the emergent molecular biology. I will also argue that sequencing deserves a history in its own right as a practice and not as a technique subordinated to the development of molecular biology or genomics. My proposed history of sequencing leads to a reappraisal of current STS debates on bioinformatics, biotechnology and biomedicine. (shrink)

Fred Sanger, the inventor of the first protein, RNA and DNA sequencing methods, has traditionally been seen as a technical scientist, engaged in laboratory bench work and not interested at all in intellectual debates in biology. In his autobiography and commentaries by fellow researchers, he is portrayed as having a trajectory exclusively dependent on technological progress. The scarce historical scholarship on Sanger partially challenges these accounts by highlighting the importance of professional contacts, institutional and disciplinary moves in his career, spanning (...) from 1940 to 1983. This paper will complement such literature by focusing, for the first time, on the transition of Sanger's sequencing strategies from degrading to copying the target molecule, which occurred in the late 1960s as he was shifting from protein and RNA to DNA sequencing, shortly after his move from the Department of Biochemistry to the Laboratory of Molecular Biology, both based in Cambridge (UK). Through a reinterpretation of Sanger's papers and retrospective accounts and a pioneering investigation of his laboratory notebooks, I will claim that sequencing shifted from the working procedures of organic chemistry to those of the emergent molecular biology. I will also argue that sequencing deserves a history in its own right as a practice and not as a technique subordinated to the development of molecular biology or genomics. My proposed history of sequencing leads to a reappraisal of current STS debates on bioinformatics, biotechnology and biomedicine. (shrink)

During the evolution of aerobic life, antioxidant defence systems developed that either directly prevent oxidative modifications of the cellular constituents or remove the modified components. An example of the latter is the proteasome, which removes cytosolic oxidised proteins. Recently, a novel mechanism of activation of the nuclear 20S proteasome was discovered: automodified poly‐(ADP‐ribose) polymerase‐1 (PARP‐1) activates the proteasome to facilitate selective degradation of oxidatively damaged histones. Since activation of the PARP‐1 itself is induced by DNA damage and is supposed to (...) play a role in DNA repair, these new results suggest a joint role of PARP‐1 in the removal of oxidised nucleoproteins and in DNA repair. We hypothesise that PARP‐1 could provide a co‐ordinative link between two nuclear antioxidant defence systems, whose concerted activation would produce a fast and efficient restoration of the native chromatin structure following oxidative stress. BioEssays 24:1060–1065, 2002. © 2002 Wiley‐Periodicals, Inc. (shrink)

In this book, T. L. Short corrects widespread misconceptions of Peirce's theory of signs and demonstrates its relevance to contemporary analytic philosophy of language, mind and science. Peirce's theory of mind, naturalistic but nonreductive, bears on debates of Fodor and Millikan, among others. His theory of inquiry avoids foundationalism and subjectivism, while his account of reference anticipated views of Kripke and Putnam. Peirce's realism falls between 'internal' and 'metaphysical' realism and is more satisfactory than either. His pragmatism is not (...) verificationism; rather, it identifies meaning with potential growth of knowledge. Short distinguishes Peirce's mature theory of signs from his better-known but paradoxical early theory. He develops the mature theory systematically on the basis of Peirce's phenomenological categories and concept of final causation. The latter is distinguished from recent and similar views, such as Brandon's, and is shown to be grounded in forms of explanation adopted in modern science. (shrink)

This article aims to examine journalists' adversarial challenges within the Australian political news interview. Within the Australian context, journalists tend to challenge interviewees: by challenging the content of the prior turn, by `interrupting' the prior turn, and by initially presenting their challenge as a freestanding assertion, not attributed to a third party. As a result, journalists could be interpreted as expressing their own perspective on the topic at hand, rather than maintaining a neutralistic stance. Although the challenging nature of journalistic (...) questions has been previously noted within the Australian context, there have been few analyses of such challenges. Using the framework of conversation analysis, the aim of the following article is to examine adversarial challenges in more detail. In particular, the article will focus on how interviewers and interviewees collaboratively produce the political news interview in such a way as to avoid accusations of bias or non-neutrality. First, the article will focus on the challenging nature of the IR's turn, by examining the various techniques used by journalists to ensure that they maintain a neutralistic stance. Second, it will examine the way in which IEs respond to such adversarial challenges. It will show how although politicians do not overtly accuse IRs of bias or impartiality, they clearly orient to the challenging nature of the journalists' turn. (shrink)

In this book, T. L. Short places the notorious difficulties of Peirce's important writings in a more productive light, arguing that he wrote philosophy as a scientist, by framing conjectures intended to be refined or superseded in the inquiries they initiate. He argues also that Peirce held that the methods and metaphysics of modern science are amended as inquiry progresses, making metaphysics a branch of empirical knowledge. Additionally, Short shows that Peirce's scientific work expanded empiricism on empirical grounds, (...) grounding his phenomenology and subverting the fact/value dichotomy, and that he understood statistical explanations in nineteenth-century science as reintroducing the idea of final causation, now made empirical. Those innovations underlie Peirce's late ideas of a normative science and of philosophy as a branch of science. Short's rich and original study shows us how to read Peirce's writings and why they are worth reading. (shrink)

W. B. Gallie's words about Peirce's cosmology—"the black sheep or white elephant of his philosophical progeny" (1952, p. 216)—have often been quoted, usually as a preface to giving a better account of the animal. That he attributed the view to 'contemporary philosophers' and did not assert it himself has usually been ignored. True, Gallie did argue that the "cosmology is a failure, and an inevitable failure" (p. 236), but he also said that Peirce himself "recognized … that his work in (...) this field was imperfect and sketchy" (p. 215), and he concluded the chapter, and his book, with an extremely sympathetic account of all that is nevertheless of enduring value in that failure. After studying Peirce's writings of his.. (shrink)

There has recently been a good deal of controversy about Landauer's Principle, which is often stated as follows: The erasure of one bit of information in a computational device is necessarily accompanied by a generation of kT ln 2 heat. This is often generalised to the claim that any logically irreversible operation cannot be implemented in a thermodynamically reversible way. John Norton (2005) and Owen Maroney (2005) both argue that Landauer's Principle has not been shown to hold in general, and (...) Maroney offers a method that he claims instantiates the operation reset in a thermodynamically reversible way. In this paper we defend the qualitative form of Landauer's Principle, and clarify its quantitative consequences (assuming the second law of thermodynamics). We analyse in detail what it means for a physical system to implement a logical transformation L, and we make this precise by defining the notion of an L-machine. Then we show that logical irreversibility of L implies thermodynamic irreversibility of every corresponding L-machine. We do this in two ways. First, by assuming the phenomenological validity of the Kelvin statement of the second law, and second, by using information-theoretic reasoning. We illustrate our results with the example of the logical transformation 'reset', and thereby recover the quantitative form of Landauer's Principle. (shrink)

Peirce earned his keep making measurements, mainly of gravity but also astronomical, and he made several contributions to the science of measurement. It has been said that his experience measuring had philosophical consequences: his adoption of fallibilism, his argument against necessitarianism, and his conception of inquiry as converging on the truth have all been mentioned. But not much attention has been paid to the curious episode of his making “the study of great men” part of a course in logic: students (...) were asked to rank a long list of men by order of greatness. That was at Johns Hopkins in 1883. I shall argue that that study, together with his reflections on pre-instrumental estimates of stars’ brightness, bears directly on the method of phaneroscopy formulated nearly two decades later. In each case, the problem is to show how objectivity is possible under conditions in which it must seem that objectivity is impossible. (shrink)

This essay contends that while Nancy and Esposito have strikingly similar concepts of the place of the political in post-metaphysical community, their respective articulations of these concepts noticeably diverge. Because of his commitment to excavating the political project of immunity as central to the Western political tradition in and through the category of the legal person, Esposito announces community as impolitical, as the interruptive spacing, and thus alternating displacement, of the political conceived as the site of emancipatory agency. In contrast, (...) in the work of Agamben and in the recent work of Nancy, an articulation of the person and the political in more agential terms can be found. This divergence presents interpretive difficulties insofar as Esposito's discussion of community as impolitical could be read as advancing ontological neutrality or passivity that threatens to separate political activity from its liberating potential. I argue that such ontological neutrality is a product of Esposito's confrontation with the political as dominated by both the logic of immunity and an engagement with the complex legacy of Heidegger's problematic political trajectory. To this extent it is an open question whether Esposito's project leaves room for a new vision of the political and for political agency. (shrink)

Geoffrey Short; Prejudice, Power and Racism: some reflections on the anti-racist critique of multi-cultural education, Journal of Philosophy of Education, Volum.

Two aspects of Peirce’s mature philosophy seem to me not to have been sufficiently appreciated. They are its empiricist method and its continuity with his scientific research. The research led to and justified the method.1Ground must be cleared before we can proceed. Simplistic ideas of the empirical must be swept aside and Peirce’s empiricism accurately identified. We must also distinguish two theories of meaning that have been associated with empiricist philosophies and show that Peirce combined them ; this will be (...) essential to Section 6. Only then can we get down to work. Peirce’s experimental and other studies of observation showed that a science of.. (shrink)

This chapter examines the ways in which French philosopher Gilles Deleuze offers conceptual resources for an enactive account of language, in particular his extensive consideration of language in The Logic of Sense. Specifically, Deleuze’s distinction between the nonsense of Lewis Carroll’s portmanteau creations and that of Antonin Artaud’s “transla- tion” of Carroll’s Jabberwocky highlights the need for an enactive, rather than merely embodied, approach to sense-making, particularly with regard to the general category of what Jakobson and Halle (1956) call “sound (...) symbolism”. (shrink)

The health benefits of male circumcision are wide rangingIn this issue, John Hutson has reiterated the conventional Western medical view that “the surgical argument for circumcision of all neonatal males at present is very weak” and he criticises many of the circumcisions performed in later childhood, without anaesthesia, as “physically cruel and potentially dangerous” [see page 238].1 He is also of the opinion that “the diseases which circumcision is able to prevent are uncommon or even rare”. But therein he errs, (...) and greatly errs.He cites only two publications dealing with the protective effect of male circumcision against HIV infection, and makes no mention of the important recent meta-analysis of Weiss, Quigley, and Hayes2 which shows conclusively from a large number of studies that …. (shrink)

The British government recently announced its willingness to expand the number of state–funded faith schools. It was a decision that aroused considerable controversy, with much of the unease centring around the allegedly divisive nature of such schools. In this article I defend faith schools against the charge that they necessarily undermine social cohesion and show how they can, in fact, legitimately be seen as a force for unity. In addition, I challenge the critics’ key assumption that non–denominational schools are inherently (...) better positioned than their faith–based counterparts to promote a tolerant society. (shrink)

The British government recently announced its willingness to expand the number of state–funded faith schools. It was a decision that aroused considerable controversy, with much of the unease centring around the allegedly divisive nature of such schools. In this article I defend faith schools against the charge that they necessarily undermine social cohesion and show how they can, in fact, legitimately be seen as a force for unity. In addition, I challenge the critics’ key assumption that non–denominational schools are inherently (...) better positioned than their faith–based counterparts to promote a tolerant society. (shrink)

This article, originally delivered at the Third Oxford International Newman Conference (Somerville College, 15 August 2004), looks at the long association between Newman and Gladstone and finds a combative mutual respect that survived not only Newman’s conversion but also Gladstone’s attack against Pope Pius IX and English Roman Catholics.

This book is remarkable for what it does not do. It purports to be about Peirce's opposition to nominalism, but it never states clearly what nominalism is and says little about Peirce's realist alternative. It contains no historical discussion of nominalism and thus does not explain the relation of Peirce's idiosyncratic use of that term to its original meaning. It ignores the secondary literature on that topic and does not even list Rosa Mayorga's highly relevant 2007 book, From Realism to (...) Realicism [sic], in its Bibliography. Nor, despite nominalism's alleged 'threat,' does it make reference to such important recent nominalists as Nelson Goodman or W.V.O. Quine. Indeed, after page one, there is hardly any.. (shrink)

Once upon a time a version of positivism prevailed in the philosophy of science. A key assumption made in positivism is that there is a class of observations - I will call them ‘basic observations’ - that are independent of theory. Basic observations are expressed in a non-theoretical or purely descriptive language: they refer to no postulated entities and presuppose no explanatory hypotheses or other logically contingent propositions. Theories, according to this philosophy, are admissible in science only if they are (...) capable of yielding some implications about the basic observations that would be made under various conditions. Theories that provide entirely different accounts of the physical world can be compared by comparing their implications for basic observation. And they are tested by comparing these implications to the basic observations that are actually made. As a general rule, if one theory is replaced by another, then all basic observations that confirmed the first must also confirm the second, but not conversely. Thus, despite revolutions even in our most fundamental theoretical conceptions, there is or can be a cumulative growth of our strictly empirical knowledge. (shrink)

The short paper introduces the concept of possible branches of double-stranded DNA (later sometimes called palindromes): Certain sequences of nucleotides may be followed, after a short unpaired stretch, by a complementary sequence in reversed order, such that each DNA strand can fold back on itself, and the DNA assumes a cruciform or tree-like structure. This is postulated to interact with regulatory proteins. -/- .

Long DNA palindromes pose a threat to genome stability. This instability is primarily mediated by slippage on the lagging strand of the replication fork between short directly repeated sequences close to the ends of the palindrome. The role of the palindrome is likely to be the juxtaposition of the directly repeated sequences by intrastrand base‐pairing. This intra‐strand base‐pairing, if present on both strands, results in a cruciform structure. In bacteria, cruciform structures have proved difficult to detect in vivo, suggesting (...) that if they form, they are either not replicated or are destroyed. SbcCD, a recently discovered exonuclease of Escherichia coli, is responsible for preventing the replication of long palindromes. These observations lead to the proposal that cells may have evolved a post‐replicative mechanism for the elimination and/or repair of large DNA secondary structures. (shrink)

: This response to my seven critics is organized under five topics: 1. The book's scope and approach; 2. Physicalism, idealism, anthropomorphism; 3. Final causation; 4. Peirce's development; 5. Signs, objects, interpretants. No ground is ceded, but I have found the interchange clarifying and hope that the reader will find it so, too.

One of the more remarkable features of the epilogue to Master Geffrei Gaimar's Estoire des Engleis is the light that it sheds both internally on the process of composition of the poem and externally on the actual sources used for its compilation and on the various individuals who had a part to play in making them available to the author. In addition to the poet himself, no fewer than nine contemporaries are named , and what appear to be four direct (...) written sources, in Latin and English, are listed . Clearly we are dealing here with an exceptionally self-conscious author, intent on establishing the highest scholarly credentials for his historico-literary enterprise and investing his text with a wide range of verifiable auctores from the England of the first half of the twelfth century. (shrink)

Peirce persistently proclaimed both idealism and realism, terms that in philosophy's history have had varied meanings, in some of which they designate opposed doctrines; his use of them also varied in meaning. The aim of Robert Lane's important new book is to trace the evolution of Peirce's idealism and realism and to show that, in the end, whatever misadventures occur en route, these doctrines, in Peirce's version of them, are not opposed. Lane explores connections to other Peircean topics: truth, pragmatism, (...) modality, generality, vagueness, continuity. However, he retains his focus, which enables him to examine Peirce's idealism and realism with extraordinary care and thoroughness.Lane's method is, in the first... (shrink)

Theory of Mind (ToM) is the term used for our ability to predict and explain the behaviour of ourselves and others. Accounts of this theory have so far fallen into two competing types: Simulation Theory and 'Theory Theory'. In contrast with Theory Theory, Simulation Theory argues that we predict behaviour not by employing a model of people, but by replicating others' thoughts and feelings. This book presents a novel defence of Simulation Theory, reviewing the major challenges against it and positing (...) the theory as the most effective method for exploring how we know each other and ourselves. Drawing on key research in the field, chapters reopen the debates surrounding Theory of Mind and cover a variety of topics including schizophrenia with implications for experimental social psychology. In the past, one of the greatest criticisms against Simulation Theory is that it cannot explain systematic error in Theory of Mind. This book explores the rapidly developing heuristics and biases programme, pioneered by Kahneman and Tversky, to suggest that a novel bias mismatch defence available to Simulation Theory explains these systematic errors. Simulation Theory: A psychological and philosophical consideration will appeal to a range of researchers and academics, including psychologists from the fields of cognitive, social and developmental psychology, as well as philosophers, psychotherapists and practitioners looking for further research on Theory of Mind. The book will also be of relevance to those interested in autism, since it offers a new approach to Theory of Mind which explains central symptoms in autistic subjects. (shrink)

Socially, people find it difficult to say ‘no’ to requests or invitations. In spoken interaction, we orient to this difficulty through the design of our responses. An agreement response is characteristically said straightaway with minimal gap between request and response. A disagreement response is characteristically delayed through silence and by prefacing the disagreement turn with tokens such as ‘well’, ‘uhm’ and ‘uh’ or with accounts as to why the recipient cannot accept the request or invitation. The question for this article (...) concerns what occurs when requests or invitations are made via texting. The results from 329 texting interactions showed that if responses to a request or invitation were delayed by more than 1 minute, it was much more likely be a ‘no’ rather than a ‘yes’ response. In other words, preferred responses were sent quickly; dispreferred responses were delayed. Understanding texting as social interaction is increasingly important as the range of communicative options continues to widen, Multimedia Messaging Service, Instant Messaging, email). This study shows preference organisation similarities between spoken interaction and texting with texters orienting to social norms concerning delayed responses. Further research is needed to understand in what contexts a person might choose one communicative medium over another. (shrink)

In empirical science, hypostatic abstraction posits an entity defined by its assumed physical relation to a known phenomenon. If the assumed relation is real, the posited entity is physically real and is not an ens rationis. The posited entity, being identified indirectly, by its relation to something else, may be the agreed-upon subject of mutually incommensurable theories, and this is a key to understanding the history of science. Natural kinds may be introduced by hypostatic abstraction, and this explains why, contrary (...) to received doctrine, concepts of natural kinds can never be vague in the sense of being fuzzy, though they can be vague in the sense of lacking specificity. Terms defined by hypostatic abstraction are rigid designators in Kripke's sense, but show how rigid designation is consistent with the Fregean theory of reference. (shrink)

Empiricism in philosophy is either a method or a theory. The two are separable: one might hold that all knowledge is empirical but that philosophy does something other than add to our knowledge, e.g., that it clarifies concepts; or one might hold that philosophy’s method is empirical and that one of the things known in that way is that not all knowledge is empirical, e.g., mathematics. And what is the empirical? If it is knowledge based on observation, then what is (...) it that can be observed? If philosophy is in method empirical, the range of the observable must be broad, perhaps including mental processes, human history, social institutions such as language, and even the difference between good and evil.In Peirce’s... (shrink)

Summary The Holocaust is now part of the history curriculum for all 11?14 year?olds in maintained schools in England and Wales. This paper directs attention to some of the ethical and pedagogic issues involved in teaching the subject. In particular, concern is expressed at the dangers of teaching it in ways likely to promote anti?Semitism. Other ethical issues raised include the extent to which freedom of speech should be permitted in the classroom; the merits or otherwise of drawing children's attention (...) to Holocaust denial; the lengths to which teachers should go in introducing children to inherently painful subject matter and the rights of parents to withdraw their children from this part of the curriculum. The question of whether to accord teachers a similar right of withdrawal is also addressed. The chief pedagogic concern of the paper is the failure of existing Holocaust curricula to take cognisance of the way children conceptualise Jewish culture and identity. Findings from some small?scale research in this area are reported and their implications discussed. (shrink)