Base pair mismatches in DNA arise from errors in DNA replication, recombination, and biochemical modification of bases. Mismatches are inherently transient. They are resolved passively by DNA replication, or actively by enzymatic removal and resynthesis of one of the bases. The first step in removal is recognition of strand discontinuity by one of the MutS proteins. Mismatches arising from errors in DNA replication are repaired in favor of the base on the template strand, but other mismatches trigger base excision or (...) nucleotide excision repair (NER), or non‐repair pathways such as hypermutation, cell cycle arrest, or apoptosis. We argue that MutL homologues play a key role in determining biologic outcome by recruiting and/or activating effector proteins in response to lesion recognition by MutS. We suggest that the process is regulated by conformational changes in MutL caused by cycles of ATP binding and hydrolysis, and by physiologic changes which influence effector availability. (shrink)

One of the twentieth-century's most exciting and challenging intellectuals, Gilles Deleuze's writings covered literature, art, psychoanalysis, philosophy, genetics, film and social theory. This book not only introduces Deleuze's ideas, it also demonstrates the ways in which his work can provide new readings of literary texts. This guide goes on to cover his work in various fields, his theory of literature and his overarching project of a new concept of becoming.

In recent decades, a new scientific approach to understand, explain, and predict many features of religion has emerged. The cognitive science of religion has amassed research on the forces that shape the tendency for humans to be religious and on what forms belief takes. It suggests that religion, like language or music, naturally emerges in humans with tractable similarities. This new approach has profound implications for how we understand religion, including why it appears so easily, and why people are willing (...) to fight-and die for it. Yet it is not without its critics, and some fear that scholars are explaining the ineffable mystery of religion away, or by showing that religion is natural proves or disproves the existence of God. An Introduction to the Cognitive Science of Religion offers students and general readers an accessible introduction to the approach, providing an overview of key findings and the debates that shape it. The volume includes a glossary of key terms, and each chapter includes suggestions for further thought and further reading as well as chapter summaries highlighting key points. This book is an indispensable resource for introductory courses on religion and a much-needed option for advanced courses. (shrink)

This essay takes a transhistorical leap to connect the philosophy of Thomas Reid to the dramatic presentation of ethical choices in Shakespeare's Macbeth. Juxtaposing the two figures reveals an underlying moral ontology common to both. This shared ontology is remarkably nuanced, ultimately affirming moral liberty whilst decisively registering the fallibility of the ‘moral faculty.’ The final section asks whether the degree of comparability warrants any further speculation, revisiting the question of a ‘common humanity.’.

Health policymakers employ utility measures to inform resource allocation decisions. They often rely on a conceptual tool called the quality-adjusted life year that discounts the value of years lived in a state of disability relative to years lived in full health. A representative sample of the general public is asked to place values on hypothetical health states as part of a standard gamble or time trade-off task. Policymakers use the resulting values to calculate the number of QALYs gained through particular (...) interventions. Utilitarian reasoning mandates that policymakers maximize QALYs gained per unit cost.Although many scholars have explored the problems of distributive justice that arise from this system... (shrink)

For the last eighteen months, I have worked with a group of disability and health policy researchers. I began this interview-based project trying to learn how these researchers’ disability identities shaped their work. How did their disability standpoint contribute to the liberatory nature of their research? I found that the disability standpoint of these researchers was in fact hard-won and grew not just out of their own disability experiences but out of their connections with the larger disability community. These connections, (...) for the most part, helped researchers come to “claim crip,” and that later influenced their research. (shrink)

Automated Influence is the use of Artificial Intelligence to collect, integrate, and analyse people’s data in order to deliver targeted interventions that shape their behaviour. We consider three central objections against Automated Influence, focusing on privacy, exploitation, and manipulation, showing in each case how a structural version of that objection has more purchase than its interactional counterpart. By rejecting the interactional focus of “AI Ethics” in favour of a more structural, political philosophy of AI, we show that the real problem (...) with Automated Influence is the crisis of legitimacy that it precipitates. (shrink)

A familiar part of debates about supererogatory actions concerns the role that cost should play. Two camps have emerged: one claiming that extreme cost is a necessary condition for when an action is supererogatory, while the other denies that it should be part of our definition of supererogation. In this paper, I propose an alternative position. I argue that it is comparative cost that is central to the supererogatory and that it is needed to explain a feature that all accounts (...) agree is central to the very notion of supererogation: optionality. Perhaps because of this agreement on its importance, few attempts have been made to clarify and explain the notion of optionality. I argue that giving an account of the optionality of supererogatory requires drawing a line between doing the bare minimum permissible and going beyond the bare minimum and that this line ought to be drawn based on comparative cost of alternative permissible acts. Having outlined my account and motivated it, I discuss and reject two concerns that might be raised: firstly, that it is extreme cost, not comparative cost, that matters and, secondly, that in fact no cost is needed for an act to be supererogatory. (shrink)

I examine the dynamics of measure development using two case studies: temperature, and health-related quality of life. I argue, following Bas van Fraassen and Leah McClimans that in each case these dynamics have a hermeneutic structure. Measure development is plagued by epistemic circularity, as is the task of interpreting a text, and similar strategies can be used in both measure development and hermeneutics to overcome that circularity. I show that Hans Georg Gadamer’s philosophical hermeneutics in particular are an effective lens (...) through which to examine the development of the temperature standard as described by Hasok Chang. Despite similar grounding in hermeneutics, I note an important difference between measure development for temperature and for health-related quality of life. Namely, while the meaning of temperature can be standardized, the meaning of health-related quality of life cannot. This standardization of meaning for the temperature concept represents a limit to the analogy with hermeneutics. Finally, I argue that the indeterminacy we find in health-related quality of life measurement is a result not only of analogy with the hermeneutic task, but of full-fledged participation in it. (shrink)

Several revisions of the Hempel and Oppenheim definition of explanation have been offered in recent years, and none have gone uncriticized in the literature. In the present paper it is argued that the difficulties involved with these attempts are based upon a confusion between three types of explanation, and that Professor David Kaplan's model of S-explanation provides a uniform treatment of all three types.

Standing in San Marco Cathedral in Venice, you immediately notice the exquisitely decorated spandrels: the triangular spaces bounded on either side by adjoining arches and by the dome above. You would be forgiven for seeing them as the starting point from which to understand the surrounding architecture. To do so would, however, be a mistake. It is a similar mistaken inference that evolutionary biologists have been accused of making in assuming a special adaptive purpose for such biological features as fingerprints (...) and chins. I argue that a mistake of just this sort is being made by ethicists who appeal to the intrinsic value of supererogatory acts in their efforts to make space for supererogation in ethical theory. Many cases of supererogatory action are simply spandrels: by-products of uncontroversial commitments elsewhere in our moral thought. This is not to downplay their value but rather to show that their value need not be the justification for making room for the supererogatory. I demonstrate this by examining two areas: rights and the distribution of burdens among a group. My argument has significance for those who take themselves to be defends of the possibility of supererogatory actions, as well as those who are committed to the contrary and those who believe themselves to be indifferent on the matter. (shrink)

This article examines the artistic potential of forms of image-making that involve registering the features of real objects using mind-independent processes. According to skeptics, these processes limit an agent’s intentional control over the features of the resultant “automatic images,” which in turn limits the artistic potential of the work, and the form as a whole. I argue that this is true only if intentional control is understood to mean that an agent produces the features of the work by their own (...) bodily movements alone. Not only is this an unrealistic standard to uphold, but I show that a definition of intentional control based on the skeptic’s position does not prohibit an agent from realizing the features of an image by means beyond their own actions. An agent can exercise intentional control over the features of an image if they successfully anticipate the effect that the remote consequences of their actions will have on these. This, I argue, entails that to exert intentional control over the features of an image is to exercise “creative agency,” which is a species of executive agency. Consequently, I defend the idea that the origin of automatic images in creative agency grounds their artistic significance. (shrink)

Visual artists and scientists frequently employ the labour of assistants and technicians, however these workers generally receive little recognition for their contribution to the production of artistic and scientific work. They are effectively “invisible”. This invisible status however, comes at the cost of a better understanding of artistic and scientific work, and improvements in artistic and scientific practice. To enhance understanding of artistic and scientific work, and these practices more broadly, it is vital to discern the nature of an assistant (...) or technician’s contribution to the production of a work, which is difficult as it is uncommon to discuss these workers. To address this, I investigate how different kinds of parallel working arrangements in collective artistic and scientific practices affect the creative potential of individuals involved. Different working arrangements permit different degrees of autonomy for individuals involved in these practices. Significantly, a lack of autonomy precludes the opportunity to act spontaneously and so exercise, what I term, “creative agency”. Evaluating the contribution of an assistant or technician based on the degree of autonomy that they are granted in the production of a work is an approach that I show can be used to precisely determine the nature of their contribution to the production of a work and accordingly, what kind of recognition an agent should receive for this. Importantly, this approach has the advantage of explaining the artistic and epistemic significance of different kinds of contribution to the production of artistic and scientific work. (shrink)

The critical realist and Bourdieusian conceptions of action fundamentally disagree on a number of fronts: the synthetic versus dualistic relationship between structure and agency; the social nature of the self/body; the link between morphogenesis and reflexivity. Despite these differences, this article argues that re-reading Bourdieu’s theories with attention to some of the core tenets of critical realism (emergence, the stratification of reality, and conjunctural causality) can provide insights into how the habitus is capable of reflexivity and social change. In particular, (...) this article reworks Bourdieu’s theory of habitus by suggesting that social selves are always situated at the intersection of multiple and competing social locations (or field positions) and that the habitus itself is always layered. Reflexivity arises from horizontal disjunctures (between field positions) and vertical disjunctures (across temporal sedimentation). (shrink)

ObjectivesTo document the auditory processing, visual attention, digit memory, phonological processing, and receptive language abilities of individual children with identified word reading difficulties.DesignTwenty-four children with word reading difficulties and 28 control children with good word reading skills participated. All children were aged between 8 and 11 years, with normal hearing sensitivity and typical non-verbal intelligence. Both groups of children completed a test battery designed to assess their auditory processing, visual attention, digit memory, phonological processing, and receptive language.ResultsWhen compared to children (...) who were good readers, children with word reading difficulties obtained significantly lower average scores on tests of auditory processing, including the frequency pattern test, gaps in noise, frequency discrimination, Dichotic Digit difference Test, and Listening in Spatialized Noise. The two groups did not differ on the discrimination measures of sinusoidal amplitude modulation or iterated rippled noise. The results from children with word reading difficulties showed that 5 children (21%) had comorbid deficits in auditory processing, visual attention, and backward digit memory; whereas 12 children (50%) had comorbid auditory processing and visual attention deficits only, and 2 children (8%) had comorbid deficits in auditory processing and digit memory; the remaining children had only auditory processing, visual attention, or digit memory deficits.ConclusionThe current study highlights the general co-existence of auditory processing, memory, and visual attention deficits in children with word reading difficulties. It is also noteworthy, however, that only one fifth of the current cohort had deficits across all measured tasks. Hence, our results also show the significant individual variability inherent in children with word reading difficulties. (shrink)

In, it was argued that Professor David Kaplan's model of S-explanation could be formulated so as to provide a unified framework for three types of explanation, viz., potential, rationally acceptable, and true. In this note I correct an error in the statement of the conditions for a potential direct S-explanans, show that the corrected version leads to a further simplification in the conditions of the model, and propose a fourth type of explanation which the framework of S-explanation can accommodate.

It is well-documented that the alteration of portrait photographs can have a negative impact on a viewer’s self-esteem. One might think that providing written disclaimers warning of alteration might help to mitigate this effect, yet empirical studies have shown that viewers continue to feel like what they are seeing is real, and thus attainable, despite knowing it is not. I propose that this cognitive dissonance occurs because disclaimers fail to show viewers how to look at the contents of a photographic (...) image differently. Consequently, viewers have the same perceptual experience, where the picture appears to faithfully resemble a direct visual experience of the subject, which conflicts with their changing sense of warrant. However, I argue that the degree of perceived similarity, and so contact, may be subject to change depending on what a viewer is attentive to during their viewing of an image, including subtle but unrealistic signs of alteration. (shrink)

Edmund Husserl was one of the very first to experience the direct impact of challenging problems in set theory and his phenomenology first began to take shape while he was struggling to solve such problems. Here I study three difficulties associated with Frege's use of sets that Husserl explicitly addressed: reference to non-existent, impossible, imaginary objects; the introduction of extensions; and 'Russell's paradox'.I do so within the context of Husserl's struggle to overcome the shortcomings of set theory and to develop (...) his own theory of manifolds. I define certain issues involved and discuss how Husserl's theory of manifolds might confront them. In so doing I hope to help bring Husserl's theories about sets and manifolds out of the realm of abstract theorizing and prompt further exploration of uncharted philosophical territory rich in philosophical implications. (shrink)

Cinema, thought and time -- Deleuze's cinema books -- Technology -- Essences -- Space and time -- Bergson, time, and life -- The movement-image -- The history of time and space and the history of cinema -- The movement-image and semiotics -- Styles of sign -- The whole of movement -- Image and life -- Becoming-inhuman, becoming imperceptible -- The deduction of the movement-image -- Art and time -- Destruction of the sensory motor apparatus and the spiritual automaton -- Time (...) and money -- Art and history -- Monument -- Framing, territorialization, and the plane of composition -- Politics and the origin of meaning -- Transcending life and the genesis of sense -- Beyond symbolic and imaginary -- Shit and money -- Exchange, gift, and theft -- The fiction of mind -- Collective investment and group fantasy -- The time of man -- The intense germinal influx. (shrink)

There has been some debate as to whether or not it is possible to keep a promise, and thus fulfil a duty, to supererogate. In this paper, I argue, in agreement with Jason Kawall, that such promises cannot be kept. However, I disagree with Kawall’s diagnosis of the problem and provide an alternative account. In the first section, I examine the debate between Kawall and David Heyd, who rejects Kawall’s claim that promises to supererogate cannot be kept. I disagree with (...) Heyd’s argument, as it fails to get to the heart of the problem Kawall articulates. Kawall’s argument however fails to make clear the problem with promising to supererogate because his discussion relies on the plausibility of the following claim: that supererogatory actions cannot also fulfil obligations. I argue that this view is mistaken because there are clear examples of supererogatory actions that also fulfil obligations. In the final section, I give my alternative account of the problem, identifying exactly what is wrong with fulfilling a duty, and thus keeping a promise, to supererogate. My diagnosis emphasises the importance of identifying non-supererogatory actions when it comes to understanding the way in which supererogatory actions go above and beyond the call of duty. (shrink)

Abstract: Groundwork is lain for answering questions as to how to situate Husserl’s theory of functions in relation to Frege’s. I examine Husserl’s ideas about analyticity and mathematics, logic and mathematics, formalization, calculating with concepts and propositions, the foundations of arithmetic, extensions to show that, although he knew, studied and lauded Frege’s ideas about functions and concepts, each man approached the issues from different angles. Seduced by the siren of transcendental phenomenology Husserl did not pursue the issues, implications, and consequences (...) of his ideas about functions. I ask whether so doing could provide new insight into, or even solutions to, the problems involving functions that beset Frege, Russell and have beset their successors. (shrink)

This chapter uses Marx’s credit theory in Comments on James Mill and Freire’s theory of the banking model of education from Pedagogy of the Oppressed to argue that the confluence of massive student debt and structures of “banking” pedagogy in contemporary American higher education places many university students in a unique position of dehumanization. The material limitations brought about by the loan are compounded by the social limitations of a resulting push toward productivity in education. Students with loan debt are (...) driven in the direction of business and pre-professional majors and away from the humanities and other fields which would facilitate students’ abilities to critically question the dehumanizing aspects of their situation. (shrink)

Nietzsche’s interest in tragedy continues throughout his work. And yet scholarship on Nietzsche’s account of tragedy has focused almost exclusively on his first book, The Birth of Tragedy – a work which is in many ways discontinuous with his more mature philosophical views. In this paper, I aim to illuminate Nietzsche’s post-Birth of Tragedy views on tragedy by setting them in the context of a particular historical conversation. Ever since Plato banished the tragic poets from the kallipolis, various philosophers have (...) attempted to respond to his challenge to offer a ‘defense of poetry’. What Nietzsche offers, I argue, is a distinctive form of response to Plato’s challenge. I show how Nietzsche takes seriously Plato’s worries, and even ends up in partial agreement with him: tragedy is not (unqualifiedly) valuable; it can be spiritually dangerous. Key to Nietzsche’s account is a distinction he draws between two types of tragic audience. For the ‘lower types’, tragedy is – as Plato feared – dangerous. For the ‘higher types’, however, tragedy can act as a regenerative force. Finally, I discuss a distinctive form of value that tragedy makes available to a modern audience: tragedy can act as a stimulus towards the process of the revaluation of values. (shrink)

The notion of supererogation—going above and beyond the call of duty—is typically discussed in a moral context. However, in this paper we argue for the existence of rationally supererogatory actions: that is, actions that go above and beyond the call of rational duty. In order to establish the existence of such actions, we first need to overcome the so-called paradox of supererogation: we need to provide some explanation for why, if some act is rationally optimal, it is not the case (...) that we are rationally required to carry out that act. We argue that a response to this ‘paradox’ can be found by reflecting on normative conflicts: cases where what is best according to some normative domain is different from what is best according to some other normative domain. (shrink)

L'unique tâche philosophique de Lequier a consisté dans la recherche d'une première vérité. Le récit existentiel est la voie qu'il a choisie. Cette voie, loin de mettre en question la métaphysique, expose, sous une forme phénoménologique, comment la vérité peut s'accomplir comme liberté dans l'histoire grâce à laquelle un être humain affirme son identité.

Traduction et édition critique des manuscrits médicaux (1666-1670) sur la respiration, les maladies, l'anatomie, l'art médical, son progrès et ses méthodes, l'ouvrage interroge l'identité de Locke philosophe à partir de ses années de formation à la médecine et à la chimie à Oxford.

Moral theories that demand that we do what is morally best leave no room for the supererogatory. One argument against such theories is that they fail to realize the value of autonomy: supererogatory acts allow for the exercise of autonomy because their omissions are not accompanied by any threats of sanctions, unlike obligatory ones. While this argument fails, I use the distinction it draws – between omissions of obligatory and supererogatory acts in terms of appropriate sanctions – to draw a (...) parallel with psychological perfectionism. Through this parallel, I demonstrate that requiring what is morally best is in fact counter-productive. Thus, by its own lights, a theory that wants us to do what is best ought at the very least to tell us to believe that some actions are supererogatory. As the old adage goes, the best is the enemy of the good; I argue here that the supererogatory is the solution. (shrink)

International economic law is peculiar. It claims universal character, yet eschews engagement with many, if not all, the racialised features of the global political economy. Its scholars mostly ignore imperialism, colonialism, and capitalism; they exclude slavery, predation, and racism altogether. In the following article, we draw upon Walter Rodney’s dialectics of development to offer a racial capitalist critique of international economic law. The disciplinary boundaries and operative logic normalised by its denizens corral us in a white, Eurocentric episteme. Ahistoricism, decontextualisation, (...) and externalisation are three epistemic devices at the forefront of the exclusionary discourse of IEL. In this space, the histories and epistemologies of Black peoples are ghettoised, treated as alien to the framework. After identifying this bias, we use the Black Radical Tradition to evaluate IEL’s amenability to the racial capitalism critique. (shrink)

Amy saves a man from drowning despite the risk to herself, because she is moved by his plight. This is a quintessentially supererogatory act: an act that goes above and beyond the call of duty. Beth, on the other hand, saves a man from drowning because she wants to get her name in the paper. On this second example, opinions differ. One view of supererogation holds that, despite being optional and good, Beth’s act is not supererogatory because she is not (...) praiseworthy; the other agrees that Beth is not praiseworthy but holds that her act is nevertheless supererogatory because, while supererogatory actions are generally performed by praiseworthy agents, an individual need not be praiseworthy for their act to be supererogatory. In this paper, I raise a problem for this latter position, which I shall call the Anti-Motivation View of supererogation. While the Anti-Motivation View rejects the claim that the agent’s motivations are important, it accepts that the agent’s intentions are. Thus, this view assumes that a clear, coherent distinction can be drawn between intentions and motivations in the context of supererogation. This distinction is often attributed to Mill; however, his original discussion reveals an inconsistency. Consider Clara, who saves a man from drowning because she wants to torture him later. According to Mill, Clara’s act is not morally good; those who follow Mill will have to accept that it is therefore not supererogatory. Mill asserts that Clara’s act differs from Amy’s and Beth’s not just in motivation but also in intention. I question this explanation and demonstrate that the distinction between motivation and intention is not as clear as the Anti-Motivation View has supposed and that the gap between the Anti-Motivation View and the alternative Praise-Based View is either much greater or much smaller than previously thought. (shrink)

Autonomy is a vital concept in much of modern theory, defining the Subject as capable of self-governance. Democratic theory relies on the concept of autonomy to provide justification for participatory government and the normative goal of democratic governance, which is to protect the ability of the individual to self-govern. Offering the first examination of the concept of autonomy from a postfoundationalist perspective, _The Autonomous Animal _analyzes how the ideal of self-governance has shaped everyday life. Claire E. Rasmussen begins by (...) considering the academic terrain of autonomy, then focusing on specific examples of political behavior that allow her to interrogate these theories. She demonstrates how the adolescent—a not-yet-autonomous subject—highlights how the ideal of self-governance generates practices intended to cultivate autonomy by forming the individual’s relationship to his or her body. She points up how the war on drugs rests on the perception that drug addicts are the antithesis of autonomy and thus must be regulated for their own good. Showing that the animal rights movement may challenge the distinction between human and animal, Rasmussen also examines the place of the endurance athlete in fitness culture, where self-management of the body is the exemplar of autonomous subjectivity. (shrink)