To decode the function and molecular recognition of several recently discovered cytosine derivatives in the human genome – 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine – a detailed understanding of their effects on the structural, chemical, and biophysical properties of DNA is essential. Here, we review recent literature in this area, with particular emphasis on features that have been proposed to enable the specific recognition of modified cytosine bases by DNA-binding proteins. These include electronic factors, modulation of base-pair stability, flexibility, and radical changes (...) in duplex conformation. We explore these proposals and assess whether or not they are supported by current biophysical data. This analysis is focused primarily on the properties of epigenetically modified DNA itself, which provides a basis for discussion of the mechanisms of recognition by different proteins. 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine have recently been discovered in mammalian DNA and appear to have essential regulatory roles. Here, we summarize recent investigations into their effects on the structural, chemical, and biophysical properties of DNA, an understanding of which is essential to decoding their behavior in the genome. (shrink)

Physicians play a critical role in preventing and treating firearm injury, although the scope of that role remains contentious and lacks systematic definition. This piece aims to utilize the fundamental principles of medical ethics to present a framework for physician involvement in firearm violence. Physicians' agency relationship with their patients creates ethical obligations grounded on three principles of medical ethics — patient autonomy, beneficence, and nonmaleficence. Taken together, they suggest that physicians ought to engage in clinical screening and treatment related (...) to firearm violence. The principle of beneficence also applies more generally, but more weakly, to relations between physicians and society, creating nonobligatory moral ideals. Balanced against physicians' primary obligations to patient agency relationships, general beneficence suggests that physicians may engage in public advocacy to address gun violence, although they are not ethically obligated to do so. A fourth foundational principle — justice — requires that clinicians attempt to ensure that the benefits and burdens of healthcare are distributed fairly. (shrink)

Background: Family members are often required to act as substitute decision-makers when health care or research participation decisions must be made for an incapacitated relative. Yet most families are unable to accurately predict older adult preferences regarding future health care and willingness to engage in research studies. Discussion and documentation of preferences could improve proxies' abilities to decide for their loved ones. This trial assesses the efficacy of an advance planning intervention in improving the accuracy of substitute decision-making and increasing (...) the frequency of documented preferences for health care and research. It also investigates the financial impact on the healthcare system of improving substitute decision-making. Methods/DesignDyads (n = 240) comprising an older adult and his/her self-selected proxy are randomly allocated to the experimental or control group, after stratification for type of designated proxy and self-report of prior documentation of healthcare preferences. At baseline, clinical and research vignettes are used to elicit older adult preferences and assess the ability of their proxy to predict those preferences. Responses are elicited under four health states, ranging from the subject's current health state to severe dementia. For each state, we estimated the public costs of the healthcare services that would typically be provided to a patient under these scenarios. Experimental dyads are visited at home, twice, by a specially trained facilitator who communicates the dyad-specific results of the concordance assessment, helps older adults convey their wishes to their proxies, and offers assistance in completing a guide entitled My Preferences that we designed specifically for that purpose. In between these meetings, experimental dyads attend a group information session about My Preferences. Control dyads attend three monthly workshops aimed at promoting healthy behaviors. Concordance assessments are repeated at the end of the intervention and 6 months later to assess improvement in predictive accuracy and cost savings, if any. Copies of completed guides are made at the time of these assessments. DiscussionThis study will determine whether the tested intervention guides proxies in making decisions that concur with those of older adults, motivates the latter to record their wishes in writing, and yields savings for the healthcare system. Trial RegistrationISRCTN89993391. (shrink)

When we hear about a transgression, we may consider whether the perpetrator’s individual circumstances make their transgression more understandable or excusable. Mitigating circumstances may reduce the severity of punishment that is deemed appropriate, both intuitively and legally. But importantly, in courts of public opinion and of law, mitigating information is typically presented only after information about a perpetrator’s transgression. We explore whether this sequence influences the force of mitigating evidence. Specifically, in two studies, we examined whether presenting evidence about a (...) perpetrator’s background before or after evidence of their violation influenced how severely U.S. participants punished perpetrators. In Study 1 (N = 132), evidence about the perpetrator’s mitigating circumstances reduced punishment only when it was presented before evidence about the perpetrator’s violation. Study 2 (N = 316) additionally revealed this moderating effect of presentation order across a variety of premeditated and impulsive violations. These findings are consistent with person-centered theories of punishment and with the Story Model of adjudication. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:GOD'S KNOWLEDGE OF FUTURE CONTINGENTS: A REPLY TO WILLIAM LANE CRAIG DAVID B. BURRELL, c.s.c. University of Notre Dame Notre Dame, Indiana IT IS FORTUNATE that other duties kept me from responding to William Lane Craig's "Aquinas on God's Knowledge of Future Contingents" when it came out (Thomist 54 [1990]: 33-79), for my initial perusal found me at once impressed and dismayed, and quite unable to disentangle (...) the two responses. A more careful subsequent reading allows me, I believe, to pinpoint where he goes wrong in reaching the conclusion which he does, yet to do so in such a way as to send readers back to an essay which is otherwise quite remarkable in the way it learns from Aquinas and offers us useful ways to read him on these perplexing issues. In doing so, he corrects many a misreading, and amasses sufficient textual and conceptual clarifications as almost to correct his own misreading. And best of all, I can hope that my rejoinder will send readers back to Aquinas above all. Indeed, one cannot but feel that the current climate of controversy regarding the proper understanding of his nuanced synthesis in philosophical theology would please Aquinas far more than attempts earlier in this century to distill it all into a " doctrine." Craig's conclusion reads: In maintaining that God's knowledge is the cause of everything God knows, Thomas transforms the universe into a nexus which, though freely chosen by God, is causally determined from above, thus eliminating human freedom (79). I shall claim that he reaches this conclusion only because ( 1) he presumes God's knowledge to be propositional knowing (52-53), 317 318 DAVID B. BURRELL, C.S.C. even though he asserts that it is not (60, n.61); and (2) that such a presumption leads him to overlook the vast difference between scientia visionis and scientia simplicis intelligentiae, though he insists on the difference and formulates it nicely in parallel with practical and speculative knowing in God (40). Such presumptions about divine knowing are not uncommon, of course, and what they lead to is one's overlooking what Josef Pieper called the "hidden element in the philosophy of St. Thomas "-creation. Indeed, my critique could begin there, remarking how Craig's careful delineation of Aquinas on God's eternal knowing of contingent things proceeds oblivious of the central fact that God's knowing in such cases is that of a creator (" In summary, then, Thomas has appealed e%clusively to the tradition of God's timelessness in order to defuse the threat of fatalism" [61, emphasis mine]). The simple observation that the God in question is always the free creator of all-that-is would have allowed him to see that Aquinas does not make the relation of God to contingents turn solely on that of an eternal knower of temporal things, but that the eternity/time relation subserves that of creator/creature. (This ordering is the more crucial, we shall see, for its power to correct the endemic tendency to equate " eternal " with " timeless," which Craig manifests throughout.) And despite Pieper's reminder that creation is largely hidden, it remains sufficiently present to a careful reader that Craig must indeed confront it at the end. Yet by the time he does so, his earlier presumptions have led him to complain that Aquinas's insistence that "God's knowledge is the causa essendi of the things that are going to happen... seems nearly unintelligible " (73). Indeed what I shall offer as the key to resolving his crucial dilemmas, and so overturning his stated conclusion, Craig introduces as a " final issue [which] threatens to undermine Thomas's attempt to preserve contingency in the face of divine knowledge, [viz.] his doctrine that God's knowledge is the cause of its objects rather than the objects' being the cause of God's knowledge" (70-71). The theologian in me would prefer to begin right here, with the radical eruption into an Aristotelian world of a free creator, GOD'S KNOWELDGE OF FUTURE CONTINGENTS 319 whose relation to the universe is indeed such as to turn our sense of knowing inside-out.1... (shrink)

We are used to seeing foundations linked to the mainstream mathematics of the late nineteenth century: the arithmetization of analysis, non-Euclidean geometry, and the rise of abstract structures in algebra. And a growing number of case studies bring a more philosophy-of-science viewpoint to the latest mathematics, as in [Carter, 2005; Corfield, 2006; Krieger, 2003; Leng, 2002]. Mac Lane's autobiography is a valuable bridge between these, recounting his experience of how the mid- and late-twentieth-century mainstream grew especially through Hilbert's school.An (...) autobiography at age 94 obviously has a lot of ground to cover. Mac Lane entered Yale in 1926 to study chemistry as a good practical career field but by the end of his first year he had won a $50 prize in mathematics and learned that you could make a living with it—as an actuary. He decided to do that. The next year he was excited to learn from his philosophy professor F.S.C. Northrop that you can also pursue new mathematical discoveries! Northrop had studied with A.N. Whitehead and sold Mac Lane on the excitement of Principia Mathematica. In a pattern that foreshadowed his career Mac Lane bought and annotated a copy of the first volume of Principia but his planned tutorial study of the book turned into a study of [Hausdorff, 1914] applying set theory to topology and analysis. As a graduate student at Chicago he was powerfully influenced by E.H. Moore, who taught the new axiomatic methods as tools for unifying and advancing the most classical analysis . Then he went to Göttingen. He heard Hilbert lecture on philosophy. He studied mathematics and its philosophy with Weyl. He followed Noether's lectures on abstract algebra for number theory. He had gone there to study logic and he wrote a …. (shrink)

Socrates wrote nothing; Plato's accounts of Socrates helped to establish western politics, ethics, and metaphysics. Both have played crucial and dramatically changing roles in western culture. In the last two centuries, the triumph of democracy has led many to side with the Athenians against a Socrates whom they were right to kill. Meanwhile the Cold War gave us polar images of Plato as both a dangerous totalitarian and an escapist intellectual. And visions of Plato have proliferated at the heart of (...) postmodern critiques of the very idea of metaphysics and politics. Plato's Progeny begins with an account of modern responses to the trial of Socrates and the controversial question of Socrates' relation to Plato. At its centre are two chapters exploring the idea of Platonic origins in and for philosophy, and of Platonic foundations for philosophical politics. Exploring unfamiliar as well as familiar invocations of Plato, Melissa Lane argues that twentieth-century ideological battles have obscured the importance of Socratic individualism, the nature of Platonic ethics, and the value of Platonic politics. Succinct and clearly written, this is an ideal guide for everyone interested in the way philosophers are still writing footnotes to Plato. (shrink)

The human tumour suppressor protein p53 is critical for regulation of the cell cycle on genotoxic insult. When DNA is damaged by radiation, chemicals or viral infection, cells respond rapidly by arresting the cell cycle. A G1 arrest requires the activity of wild‐type p53, as it is not observed in cells lacking functionally wild‐type protein, and at least some component of S phase and G2/M arrests is also thought to be p53‐dependent. p53 functions as a transcription factor which binds specific (...) DNA sequences, and recently major downstream targets have been identified, including p21Cip1 an inhibitor of the cell cycle kinases that also blocks the replicative but not the repair function of DNA polymerase δ auxiliary factor, PCNA. Current interest focuses on developing novel cancer therapies based on our knowledge of the activity of p53 and p21Cip1 in the cell cycle. (shrink)

It has been convincingly argued that computer simulation modeling differs from traditional science. If we understand simulation modeling as a new way of doing science, the manner in which scientists learn about the world through models must also be considered differently. This article examines how researchers learn about environmental processes through computer simulation modeling. Suggesting a conceptual framework anchored in a performative philosophical approach, we examine two modeling projects undertaken by research teams in England, both aiming to inform flood risk (...) management. One of the modeling teams operated in the research wing of a consultancy firm, the other were university scientists taking part in an interdisciplinary project experimenting with public engagement. We found that in the first context the use of standardized software was critical to the process of improvisation, the obstacles emerging in the process concerned data and were resolved through exploiting affordances for generating, organizing, and combining scientific information in new ways. In the second context, an environmental competency group, obstacles were related to the computer program and affordances emerged in the combination of experience-based knowledge with the scientists’ skill enabling a reconfiguration of the mathematical structure of the model, allowing the group to learn about local flooding. (shrink)

This book offers a new interpretation of the metaphysics of Charles Peirce, the founder of pragmatism and one of America's greatest philosophers. Robert Lane begins by examining Peirce's basic realism, his belief in a world that is independent of how anyone believes it to be. Lane argues that this realism is the basis for Peirce's account of truth, according to which a true belief is one that would be settled by investigation and that also represents the real world. (...) He then explores Peirce's application of his Pragmatic Maxim to clarify the idea of reality, his two forms of idealism, and his realism about generality and vagueness. This rich study will provide readers with a clear understanding of Peirce's thoughts on reality and truth and how they intersect, and of his views on the relation between the mind and the external world. (shrink)

Current UK legislation is impacting upon the feasibility and cost-effectiveness of medical record-based research aimed at benefiting the NHS and the public heath. Whereas previous commentators have focused on the Data Protection Act 1998, the Health and Social Care Act 2001 is the key legislation for public health researchers wishing to access medical records without written consent. The Act requires researchers to apply to the Patient Information Advisory Group for permission to access medical records without written permission. We present a (...) case study of the work required to obtain the necessary permissions from PIAG in order to conduct a large scale public health research project. In our experience it took eight months to receive permission to access basic identifying information on individuals registered at general practices, and a decision on whether we could access clinical information in medical records without consent took 18 months. Such delays pose near insurmountable difficulties to grant funded research, and in our case £560 000 of public and charitable money was spent on research staff while a large part of their work was prohibited until the third year of a three year grant. We conclude by arguing that many of the current problems could be avoided by returning PIAG’s responsibilities to research ethics committees, and by allowing “opt-out” consent for many public health research projects. (shrink)

Current UK legislation is impacting upon the feasibility and cost-effectiveness of medical record-based research aimed at benefiting the NHS and the public heath. Whereas previous commentators have focused on the Data Protection Act 1998, the Health and Social Care Act 2001 is the key legislation for public health researchers wishing to access medical records without written consent. The Act requires researchers to apply to the Patient Information Advisory Group for permission to access medical records without written permission. We present a (...) case study of the work required to obtain the necessary permissions from PIAG in order to conduct a large scale public health research project. In our experience it took eight months to receive permission to access basic identifying information on individuals registered at general practices, and a decision on whether we could access clinical information in medical records without consent took 18 months. Such delays pose near insurmountable difficulties to grant funded research, and in our case £560 000 of public and charitable money was spent on research staff while a large part of their work was prohibited until the third year of a three year grant. We conclude by arguing that many of the current problems could be avoided by returning PIAG’s responsibilities to research ethics committees, and by allowing “opt-out” consent for many public health research projects. (shrink)

Sydney Shoemaker, developing an idea of Wittgenstein’s, argues that we are immune to error through misidentification relative to the first-person pronoun. Although we might be liable to error when “I” (or its cognates) is used as an object, we are immune to error when “I” is used as a subject (as when one says, “I have a toothache”). Shoemaker claims that the relationship between “I” as-subject and the mental states of which it is introspectively aware is tautological: when, say, we (...) judge that “I feel pain,” we are tautologically aware that feels pain is instantiated and that it is instantiated in oneself. Moreover, he contends that this relationship holds not just for bodily sensations, but also for the sense of agency and for visual perception. But we deny that this relationship is tautological; instead, we treat Shoemaker’s principle (IEM) as a hypothesis. We then proceed to show that certain pathological states and experimentally-induced illusions can be adduced to show that IEM describes not a necessary relationship but a contingent relationship, one that sometimes fails to obtain. That we are not immune to error in the way Shoemaker describes has grave consequences for many aspects of his ideas concerning the first-person perspective. In the course of arguing that these empirical phenomena count against IEM, we also show that not only can the content of conscious experience be misrepresented, so too can the subject: that is, not only can the what of conscious experience be misrepresented, so too can the who. (shrink)

In virtue of what does a sign have meaning? This is the question raised by Wittgenstein's rule-following considerations. Semantic dispositionalism is a (type of) theory that purports to answer this question. The present paper argues that semantic dispositionalism faces a heretofore unnoticed problem, one that ultimately comes down to its reliance on unanalyzed notions of repeated types of signs. In the context of responding to the rule-following paradox—and offering a putative solution to it—this amounts to simply assuming a solution to (...) the problem in one domain and using it to solve the same problem in another. Given, moreover, the level at which the rule-following paradox undercuts dispositionalism—the level of the notion of a sign's repetition—the objections made to the view also rule out causal/informational theories of meaning as well as communitarian/assertion-theoretic ones as potential solutions to the rule-following paradox. (shrink)

A new reading of Plato’s political thought Plato famously defends the rule of knowledge. Knowledge, for him, is of the good. But what is rule? In this study, Melissa Lane reveals how political office and rule were woven together in Greek vocabulary and practices that both connected and distinguished between rule in general and office as a constitutionally limited kind of rule in particular. In doing so, Lane shows Plato to have been deeply concerned with the roles and (...) relationships between rulers and ruled. Adopting a longstanding Greek expectation that a ruler should serve the good of the ruled, Plato’s major political dialogues—the Republic, the Statesman, and Laws—explore how different kinds of rule might best serve that good. With this book, Lane offers the first account of the clearly marked vocabulary of offices at the heart of all three of these dialogues, explaining how such offices fit within the broader organization and theorizing of rule. Lane argues that taking Plato’s interest in rule and office seriously reveals tyranny as ultimately a kind of anarchy, lacking the order as well as the purpose of rule. When we think of tyranny in this way, we see how Plato invokes rule and office as underpinning freedom and friendship as political values, and how Greek slavery shaped Plato’s account of freedom. Reading Plato both in the Greek context and in dialogue with contemporary thinkers, Lane argues that rule and office belong at the center of Platonic, Greek, and contemporary political thought. (shrink)

For millennia self has been conjectured to be necessary for consciousness. But scant empirical evidence has been adduced to support this hypothesis. Inconsistent explications of “self” and failure to design apt experiments have impeded progress. Advocates of phenomenological psychiatry, however, have helped explicate “self,” and employed it to explain some psychopathological symptoms. In those studies, “self” is understood in a minimalist sense, sheer “for-me-ness.” Unfortunately, explication of the “minimal self” (MS) has relied on conceptual analysis, and applications to psychopathology have (...) been hermeneutic, allowing for many degrees of interpretive latitude. The result is that MS’s current scientific status is analogous to that of the “atom,” at the time when “atom” was just beginning to undergo transformation from a philosophical to a scientific concept. Fortunately, there is now an opportunity to promote a similar transformation for “MS.” Discovery of the brain’s Default Mode Network (DMN) opened the door to neuroimaging investigations of self. Taking the DMN and other forms of intrinsic activity as a starting point, an empirical foothold can be established, one that spurs experimental research and that enables extension of research into multiple phenomena. New experimental protocols that posit “MS” can help explain phenomena hitherto not thought to be related to self, thereby hastening development of a mature science of self. In particular, targeting phenomena wherein consciousness is lost and recovered, as in some cases of Unresponsive Wakefulness Syndrome (UWS), allow for design of neuroimaging probes that enable detection of MS during non-conscious states. These probes, as well as other experimental protocols applied to NREM Sleep, General Anesthesia (GA), and the waking state, provide some evidence to suggest that not only can self and consciousness dissociate, MS might be a necessary precondition for conscious experience. Finally, these findings have implications for the science of consciousness: it has been suggested that “levels of consciousness” (LoC) is not a legitimate concept for the science of consciousness. But because we have the conceptual and methodological tools with which to refine investigations of MS, we have the means to identify a possible foundation—a bifurcation point—for consciousness, as well as the means by which to measure degrees of distance from that foundation. These neuroimaging investigations of MS position us to better assess whether LoC has a role to play in a mature science of consciousness. (shrink)

ABSTRACTThis paper explores and reevaluates the place of Plato in the history of liberty. In the first half, reevaluating the view that he invents a concept of ‘positive liberty’ in the Republic, I argue for two claims: that he does not do so, insofar as this is not the way that virtuous psychological self-mastery in the Republic is understood, and that the Republic works primarily with the inverse concept of slavery, relying on entrenched Greek ideas about the badness of the (...) status of being a slave and the actions and dispositions associated with it. Turning in the second half to seek Platonic innovation not in the domain of ‘positive liberty’ but in reflection on liberty as a political value, understood as the liberty of action of citizens within the laws, I argue for two further claims: that as such a political value, liberty is limited and reshaped in both the Republic and the Laws to be compatible with obedience to rule / willingness to be ruled, ideally willing obedience; and that for this limited and reshaped value to be secured, such obedience must be manifested not only in regard to a constitution’s laws, but also to the magistrates who hold office within it. (shrink)

Children and adults from theus and China heard about people who died in two types of narrative contexts – medical and religious – and judged whether their psychological and biological capacities cease or persist after death. Most 5- to 6-year-olds reported that all capacities would cease. In theus, but not China, there was an increase in persistence judgments at 7–8 years, which decreased thereafter.uschildren’s persistence judgments were influenced by narrative context – occurring more often for religious narratives – and such (...) judgments were made especially for psychological capacities. When participants were simply asked what happens to people following death, in both countries there were age-graded increases in references to burial, religious ritual, and the supernatural. (shrink)

Currently, one of the most influential theories of consciousness is Rosenthal's version of higher-order-thought (HOT). We argue that the HOT theory allows for two distinct interpretations: a one-component and a two-component view. We further argue that the two-component view is more consistent with his effort to promote HOT as an explanatory theory suitable for application to the empirical sciences. Unfortunately, the two-component view seems incapable of handling a group of counterexamples that we refer to as cases of radical confabulation. We (...) begin by introducing the HOT theory and by indicating why we believe it is open to distinct interpretations. We then proceed to show that it is incapable of handling cases of radical confabulation. Finally, in the course of considering various possible responses to our position, we show that adoption of a disjunctive strategy, one that would countenance both one-component and two-component versions, would fail to provide any empirical or explanatory advantage. (shrink)

Issues of methodology are central to the philosophy of moral progress. However, the idea that effective moral methodology, as well as being instrumental to progress, might also constitute progress has not been adequately explored. This paper will critically assess the merits of this idea – what I call ‘pure proceduralism about moral progress’ – taking Philip Kitcher's recent theory of ‘democratic contractualism’ (2021) as a test case. An epistemology of pure procedural moral progress will be sketched: namely, a naturalised epistemology (...) of paradigmatic instances of moral progress. Assuming an ideal procedure exists and has been at least approximately instantiated (an empirical claim), we learn about its form by studying paradigms of historical moral progress. From this epistemological method will be derived theoretical constraints on what can count as a theory of moral progress per se: it must capture the core semantic constraints on the term ‘moral progress,’ those features without which we would not recognise a change as moral progress. While this poses a tougher challenge for pure proceduralism than for more traditional approaches to moral methodology, it will be concluded that the potential of pure proceduralism as a viable metaethics of moral progress remains an exciting open question. (shrink)

In a recent Opinion article, Sui and Humphreys [1] argue that experimental findings suggest self is ‘special’, in that self-reference serves a binding function within human cognitive economy. Contrasting their view with other functionalist positions, chiefly Dennett's [2], they deny that self is a convenient fiction and adduce findings to show that a ‘core self representation’ serves as an ‘integrative glue’ helping to bind distinct types of information as well as distinct stages of psycho- logical processing. In other words, where (...) Dennett regards self as analogous to a center of gravity, a simplification posited by observers, Sui and Humphreys regard self as a function that modulates mental processes. In practice, however, the concept of ‘self’ they employ is not unlike Dennett's. We side with Sui and Humphreys in hold- ing that self-reference modulates mental processes: reference to self during a task can bind memory to source, increase perceptual integration, and link attention to decision making, among other things. What is more, these functions are not reducible to other factors such as semantic coding, familiarity, or reward [3]. But whereas Sui and Humphreys contribute important empirical detail, the binding functions they describe are compatible with Dennett's version of functionalism, which treats self as an artifact of social process. (shrink)

In this essay I describe two of the accounts that Peirce provides of personhood: the semiotic account, on which a person is a sequence of thought-signs, and the naturalistic account, on which a person is an animal. I then argue that these disparate accounts can be reconciled into a plausible view on which persons are numerically distinct entities that are nevertheless continuous with each other in an important way. This view would be agreeable to Peirce in some respects, as it (...) is modeled on his theory of perception, incorporates his categories of Firstness, Secondness and Thirdness, and is in harmony with his objective idealism. But it diverges from Peirce in one important respect, viz. its rejection of the idea that some groups of human beings count as persons. (shrink)

The question of whether or not God exists is profoundly fascinating and important. Now two articulate spokesmen--one a Christian, the other an atheist--duel over God's existence in an illuminating battle of ideas. In God? A Debate between a Christian and an Atheist, William Lane Craig and Walter Sinnott-Armstrong bring to the printed page two debates they held before live audiences, preserving all the wit, clarity, and immediacy of their public exchanges. Avoiding overly esoteric arguments, they directly address issues such (...) as religious experience, the Bible, evil, eternity, the origin of the universe, design, and the supposed connection between morality and the existence of God. Employing sharp and humorous arguments, each philosopher strikes quickly to the heart of his opponent's case. For example, Craig claims that we must believe in God in order to explain objective moral values, such as why rape is wrong. Sinnott-Armstrong responds that what makes rape wrong is the harm to victims of rape, so rape is immoral even if there is no God. By assuming a traditional concept of God in their discussion, the authors ensure that they are truly addressing each other's viewpoints and engaging in a disagreement over a unified issue. The book is composed of six chapters that alternate between Craig and Sinnott-Armstrong, so that each separate point can be discussed as it arises. Ideal for courses in the philosophy of religion and introduction to philosophy, this lively and direct dialogue will stimulate students and anyone interested in the existence of God, regardless of whether or not they believe in God. (shrink)

... I was many years ago led to define "real" as meaning being such as it is, no matter how you, or, I, or any man or definite collection of men may think it to be; where I use the long and awkward phrase in order to avoid all appearance of meaning independently of human thought. For obviously, nothing that I or anybody ever can mean can be independent of human thought. That is real which men would eventually and finally (...) come to think to be absolutely necessary to be thought in order to understand the truth, supposing the existence and advance in knowledge of the human race to be continued without any limitation, though I cannot pretend that I have as distinct an idea of exactly what that means as I could wish.... (shrink)

This paper outlines a defense of the project of seeking to interpret Plato’s political thought as a valid method of interpreting Plato. It does so in two stages: in the first part, by rebutting denials of the possibility of interpreting Plato’s thought at all; in the second part, by identifying one set of ideas arguably central to Plato’s political thought, namely, his profound rejection of political anarchy, understood in terms of the absence of the authority of officeholders and posited both (...) as characteristic of democracy and as the origin of tyranny. This approach to anarchy and its relationship to tyranny is, I contend, a Platonic innovation, and must be understood against the background of Greek writings that straightforwardly opposed the two. I aim here to show, on the one hand, that denying tout court the project of seeking to interpret Plato’s political thought is an implausibly extreme position, and, on the other, that pursuing that project can bear valuable fruit. (shrink)

A cursory glance at the list of Nobel Laureates for Economics is sufficient to confirm Stanovich’s description of the project to evaluate human rationality as seminal. Herbert Simon, Reinhard Selten, John Nash, Daniel Kahneman, and others, were awarded their prizes less for their work in economics, per se, than for their work on rationality, as such. Although philosophical works have for millennia attempted to describe, explicate and evaluate individual and collective aspects of rationality, new impetus was brought to this endeavor (...) over the last century as mathematical logic along with the social and behavioral sciences emerged. Yet more recently, over the last several decades, propelled by the emergence of artificial intelligence, cognitive science, evolutionary psychology, neuropsychology, and related fields, even more sophisticated approaches to the study of rationality have emerged. (shrink)

For many years, Charles Peirce maintained that all senses of the modal terms "possible" and "necessary" can be defined in terms of "states of information." But in 1896, he was motivated by his work in set theory to criticize that account of modality, and in 1905 he characterized that criticism as a return "to the Aristotelian doctrine of a real possibility ... the great step that was needed to render pragmaticism an intelligible doctrine." But since Peirce was a realist about (...) modality before 1896, and since he continued defining "possibility" in terms of "states of information" after that date, it is not clear exactly what he changed his mind about. In this essay I explain what it was that Peirce changed his mind about and why, in retrospect, he viewed that change as a decisive step in the development of pragmaticism. (shrink)

In this essay, I seek to demonstrate the interplay of philosophical voices – particularly, that of a platonist voice and a community-agreement-view voice – that drives Wittgenstein’s rule-following dialectic forward; and I argue that each voice succumbs to a particular form of dialectical oscillation that renders its response to the problem of rule-following philosophically inadequate. Finally, I suggest that, by seeing and taking stock of the dilemma in which these responses to the skeptical problem are caught, we can come to (...) appreciate Wittgenstein’s own view of what might constitute a proper a response to the so-called problem of rule-following. This view can be preliminarily characterized by saying that Wittgenstein’s aim is to dissolve the temptation to philosophically rebut the skeptical challenge posed by the rule-following dialectic, an aim he achieves by revealing the semantic emptiness of the apparent sentences that raise the skeptical problem. (shrink)

Chemiosmotic coupling − the harnessing of electrochemical ion gradients across membranes to drive metabolism − is as universally conserved as the genetic code. As argued previously in these pages, such deep conservation suggests that ion gradients arose early in evolution, and might have played a role in the origin of life. Alkaline hydrothermal vents harbour pH gradients of similar polarity and magnitude to those employed by modern cells, one of many properties that make them attractive models for life's origin. Their (...) congruence with the physiology of anaerobic autotrophs that use the acetyl CoA pathway to fix CO2 gives the alkaline vent model broad appeal to biologists. Recently, however, a paper by Baz Jackson criticized the hypothesis, concluding that natural pH gradients were unlikely to have played any role in the origin of life. Unfortunately, Jackson mainly criticized his own interpretations of the theory, not what the literature says. This counterpoint is intended to set the record straight. (shrink)

This is the first of two papers that examine Charles Peirce’s denial that human beings have a faculty of intuition. The semiotic and epistemo-logical aspects of that denial are well-known. My focus is on its neglected metaphysical aspect, which I argue amounts to the doctrine that there is no determinate boundary between the internal world of the cognizing subject and the external world that the subject cognizes. In the second paper, I will argue that the “objective idealism” of Peirce’s 1890s (...) cosmological series is a more general iteration of the metaphysical aspect of his earlier denial of intuition. (shrink)

Neural activity varies continually from moment to moment. Such temporal variability (TV) has been highlighted as a functionally specific brain property playing a fundamental role in cognition. We sought to investigate the mechanisms involved in TV changes between two basic behavioral states, namely having the eyes open (EO) or eyes closed (EC) in vivo in humans. To these ends we acquired BOLD fMRI, ASL, and [18F]-fluoro-deoxyglucose PET in a group of healthy participants (n = 15), along with BOLD fMRI and (...) [18F]-flumazenil PET in a separate group (n = 19). Focusing on an EO- vs EC-sensitive region in the occipital cortex (identified in an independent sample), we show that TV is constrained in the EO condition compared to EC. This reduction is correlated with an increase in energy consumption and with regional GABAA receptor density. This suggests that the modulation of TV by behavioral state involves an increase in overall neural activity that is related to an increased effect from GABAergic inhibition in addition to any excitatory changes. These findings contribute to our understanding of the mechanisms underlying activity variability in the human brain and its control. (shrink)

It is widely thought that, in §201 of the Philosophical Investigations, Wittgenstein reveals himself to oppose a definite view or theory of rule-following. I argue that, due to the self-undermining character of that section, no such interpretation should be accepted. Then I sketch a reading of Wittgenstein’s method that accounts for the paradoxical nature of §201, and I show how this methodology is realized in his remarks on following a rule.

This chapter presents a detailed explanation of Peirce’s early and late views on semiotic indeterminacy and then considers how those views might be applied within biosemiotics. Peirce distinguished two different forms of semiotic indeterminacy: generality and vagueness. He defined each in terms of the “right” that indeterminate signs extend, either to their interpreters in the case of generality or to their utterers in the case of vagueness, to further determine their meaning. On Peirce’s view, no sign is absolutely determinate, i.e., (...) every sign is indeterminate to at least some degree and so exhibits some degree of generality or vagueness. If Peirce was right about this, then no instance of biosemiosis is completely determinate—every biosign must be general or vague to some degree. I show that on Peirce’s view, whether a sign is general or vague depends on its immediate object, “the idea which the sign is built upon,” and I explain how Peirce would go about identifying the immediate object of a sign lacking both a minded utterer and a minded interpreter—an identification that must be possible if any biosign is indeterminate. (shrink)

Objective Manic and depressive phases of bipolar disorder (BD) show opposite psychomotor symptoms. Neuronally, these may depend on altered relationships between sensorimotor network (SMN) and subcortical structures. The study aimed to investigate the functional relationships of SMN with substantia nigra (SN) and raphe nuclei (RN) via subcortical-cortical loops, and their alteration in bipolar mania and depression, as characterized by psychomotor excitation and inhibition. -/- Method In this resting-state functional magnetic resonance imaging (fMRI) study on healthy (n = 67) and BD (...) patients (n = 100), (1) functional connectivity (FC) between thalamus and SMN was calculated and correlated with FC from SN or RN to basal ganglia (BG)/thalamus in healthy; (2) using an a-priori-driven approach, thalamus-SMN FC, SN-BG/thalamus FC, and RN-BG/thalamus FC were compared between healthy and BD, focusing on manic (n = 34) and inhibited depressed (n = 21) patients. -/- Results (1) In healthy, the thalamus-SMN FC showed a quadratic correlation with SN-BG/thalamus FC and a linear negative correlation with RN-BG/thalamus FC. Accordingly, the SN-related FC appears to enable the thalamus-SMN coupling, while the RN-related FC affects it favoring anti-correlation. (2) In BD, mania showed an increase in thalamus-SMN FC toward positive values (ie, thalamus-SMN abnormal coupling) paralleled by reduction of RN-BG/thalamus FC. By contrast, inhibited depression showed a decrease in thalamus-SMN FC toward around-zero values (ie, thalamus-SMN disconnection) paralleled by reduction of SN-BG/thalamus FC (and RN-BG/thalamus FC). The results were replicated in independent HC and BD datasets. -/- Conclusions These findings suggest an abnormal relationship of SMN with neurotransmitters-related areas via subcortical-cortical loops in mania and inhibited depression, finally resulting in psychomotor alterations. (shrink)