Class I PI 3‐kinases signal by producing the signaling lipid phosphatidylinositol(3,4,5) trisphosphate, which in turn acts by recruiting downstream effectors that contain specific lipid‐binding domains. The class I PI 3‐kinases comprise four distinct catalytic subunits linked to one of seven different regulatory subunits. All the class I PI 3‐kinases produce the same signaling lipid, PIP3, and the different isoforms have overlapping expression patterns and are coupled to overlapping sets of upstream activators. Nonetheless, studies in cultured cells and in animals have (...) demonstrated that the different isoforms are coupled to distinct ranges of downstream responses. This review focuses on the mechanisms by which the production of a common product, PIP3, can produce isoform‐specific signaling by PI 3‐kinases.Editor's suggested further reading in BioEssays: Phosphatidylinositol 4,5‐bisphosphate: Targeted production and signaling AbstractHow does SHIP1/2 balance PtdIns(3,4)P2 and does it signal independently of its phosphatase activity? Abstract. (shrink)

Contributors to this collection examine the Turners’ most important theoretical contributions to anthropology, from their work on pilgrimages, liminality, and communitas to insights from their fieldwork. They illustrate the Turners’ enduring theoretical contributions and their profound effects on the anthropological perspective.

Focal brain metabolic effects detected by proton magnetic resonance spectroscopy (MRS) in obsessive-compulsive disorder (OCD) represent prospective indices of clinical status and guides to treatment design. Sampling bilateral pregenual anterior cingulate cortex (pACC), anterior middle cingulate cortex (aMCC), and thalamus in 40 adult patients and 16 healthy controls, we examined relationships of the neurometabolites glutamate+glutamine (Glx), creatine+phosphocreatine (Cr), and choline-compounds (Cho) with OCD diagnosis and multiple symptom types. The latter included OC core symptoms (Yale-Brown Obsessive-Compulsive Scale - YBOCS), depressive symptoms (...) (Montgomery-Åsberg Depression Rating Scale - MADRS), and general functioning (Global Assessment Scale - GAS). pACC Glx was 9.7% higher in patients than controls. Within patients, Cr and Cho correlated negatively with YBOCS and MADRS, while Cr correlated positively with the GAS. In aMCC, Cr and Cho correlated negatively with MADRS, while Cr in thalamus correlated positively with GAS. These findings present moderate support for glutamatergic and cingulocentric perspectives on OCD. Based on our prior metabolic model of OCD, we offer one possible interpretation of these group and correlational effects as consequences of a corticothalamic state of elevated glutamatergic receptor activity alongside below-normal glutamatergic transporter activity. (shrink)

We believe we know our bodies intimately—that their material reality is certain and that this certainty leads to an epistemological truth about sex, gender, and identity. By exploring and giving equal weight to transgendered subjectivities, however, Gayle Salamon upends these certainties. Considering questions of transgendered embodiment via phenomenology (Maurice Merleau-Ponty), psychoanalysis (Sigmund Freud and Paul Ferdinand Schilder), and queer theory, Salamon advances an alternative theory of normative and non-normative gender, proving the value and vitality of trans experience for (...) thinking about embodiment. Salamon suggests that the difference between transgendered and normatively gendered bodies is not, in the end, material. Rather, she argues that the production of gender itself relies on a disjunction between the "felt sense" of the body and an understanding of the body's corporeal contours, and that this process need not be viewed as pathological in nature. Examining the relationship between material and phantasmatic accounts of bodily being, Salamon emphasizes the productive tensions that make the body both present and absent in our consciousness and work to confirm and unsettle gendered certainties. She questions traditional theories that explain how the body comes to be—and comes to be made one's own—and she offers a new framework for thinking about what "counts" as a body. The result is a groundbreaking investigation into the phenomenological life of gender. (shrink)

Peter Millican and Branden Thornhill-Miller have recently argued that contradictions between different religious belief systems, in conjunction with the host of defeaters based on empirical research concerning alleged sources of evidence for ‘perceived supernatural agency’, render all ‘first-order’, that is actual, religious traditions positively irrational, and a source of discord on a global scale. However, since the authors recognise that the ‘secularisation thesis’ appears to be incorrect, and that empirical research provides evidence that religious belief also has beneficial individual and (...) social effects, they put forward a hypothesis of a ‘second-order religious belief ’, with Universalist overtones and thus free of intergroup conflict, and free of irrationality, since supported (solely) by the Fine-Tuning Argument. While granting most of their arguments based on empirical research and embracing the new paradigm of the atheism/religion debate implicit in their paper, I contend that Millican’s and Thornhill-Miller’s proposal is unlikely to appeal to religious believers, because it misconstrues the nature and grounds of religious belief. I suggest that their hypothesis may be refined by taking into account a view of axiologically grounded religious belief that I refer to as ‘agatheism’, since it identifies God or the Ultimate Reality with the ultimate good (to agathon). (shrink)

This essay considers what is critical in critical phenomenology, and asks what features critical and phenomenological methods share. I suggest three fundamentally significant resonances between the critical and phenomenological enterprises. First is the suggestion that critique, like phenomenology, is an attempt to move beyond a dualism of inside and outside in order to extend into outer regions of what is known. Second is the insistence that what at first appears to be a purely negative endeavor, a finding of limit, is (...) incomplete if, upon finding that limit, it comes to a stop. Just as the reduction is not a means to banish or negate the world, but rather the condition through which it can more fully emerge, critique cannot be merely a cataloguing of the limitations of the present situation. Third is the openness to the possibilities of the world, a wonder or curiosity, that is revealed through the work of description in phenomenology, or Foucault’s characterization of philosophy not as an unmasking, but a making visible of what is visible. Finally I consider critical phenomenology’s futures: How is a newly enlivened kind of scholarship emerging from these two forms of thinking, both of which have been dismissed as outmoded or irrelevant? The new work currently emerging in phenomenology, with its emphasis on its own reflexive self-consideration and decolonization, offers hope that it might yet be capacious enough to simultaneously encompass the revelation of its limitations as well as the expansion of its reach. (shrink)

In this paper I argue that from the point of view of a theist, inclusivism with respect to the issue whether adherents of different religious traditions can have veridical experience of God (or Ultimate Reality) now, is more plausible than the Alstonian exclusivism. I suggest that mystical inclusivism of the kind I imply in this paper may contribute to the development of cross-cultural philosophy of religion, as well as to the theoretical framework for inter-religious dialogue, because (1) it allows for (...) the possibility of veridical experience of God in a variety of religious traditions, but (2) it avoids the radical revisionist postulates of Hickian pluralism and (3) it leaves open the question whether the creed of any specific tradition is a better approximation to the truth about God than the creeds of other traditions. (edited). (shrink)

Kurt Godel, the greatest logician of our time, startled the world of mathematics in 1931 with his Theorem of Undecidability, which showed that some statements in mathematics are inherently "undecidable." His work on the completeness of logic, the incompleteness of number theory, and the consistency of the axiom of choice and the continuum theory brought him further worldwide fame. In this introductory volume, Raymond Smullyan, himself a well-known logician, guides the reader through the fascinating world of Godel's incompleteness theorems. The (...) level of presentation is suitable for anyone with a basic acquaintance with mathematical logic. As a clear, concise introduction to a difficult but essential subject, the book will appeal to mathematicians, philosophers, and computer scientists. (shrink)

This paper charts the concepts of grip and the bodily auxiliary in Maurice Merleau-Ponty to consider how they find expression in disability narratives. Arguing against the notion of “maximal grip” that some commentators have used to explicate intentionality in Merleau-Ponty, I argue that grip in his texts functions instead as a compensatory effort to stave off uncertainty, lack of mastery, and ambiguity. Nearly without exception in Phenomenology of Perception, the mobilization of “grip” is a signal of impending loss, and is (...) offered as a strategy for managing failure rather than as an example of sure-footed mastery. I read Merleau-Ponty alongside Mary Felstiner's Out of Joint: A Public and Private Story of Arthritis to explore these other, attenuated dimensions of grip. Finally, the paper turns to Harriet McBryde Johnson's memoir Too Late to Die Young as an example of a way of thinking disabled embodiment otherwise. (shrink)

Ontologies have been successfully used to assign semantics in the Semantic Web context, to support integration of data from different systems or different sources, and to enable reasoning. However, building ontologies is not a trivial task. Ontology reuse can help in this matter. The search and selection of ontologies to be reused should consider the alignment between their scope and the scope of the ontology being developed. In this paper, we discuss how goal modeling can be helpful in this context (...) and we present GO-FOR, a framework in which goals are the central elements to promote ontology reuse. GO-FOR comprises a conceptual architecture, a goal-oriented ontology development process and a supporting tool. In GO-FOR we introduce Goal-Oriented Ontology Patterns as a new type of pattern to be applied to develop ontologies in a goal-oriented approach. Results of the use of GO-FOR to build an ontology used to integrate patient examination data are also shown in this paper. (shrink)

I propose to consider the question, "Can machines think?" This should begin with definitions of the meaning of the terms "machine" and "think." The definitions might be framed so as to reflect so far as possible the normal use of the words, but this attitude is dangerous, If the meaning of the words "machine" and "think" are to be found by examining how they are commonly used it is difficult to escape the conclusion that the meaning and the answer to (...) the question, "Can machines think?" is to be sought in a statistical survey such as a Gallup poll. But this is absurd. Instead of attempting such a definition I shall replace the question by another, which is closely related to it and is expressed in relatively unambiguous words. The new form of the problem can be described in terms of a game which we call the 'imitation game." It is played with three people, a man (A), a woman (B), and an interrogator (C) who may be of either sex. The interrogator stays in a room apart front the other two. The object of the game for the interrogator is to determine which of the other two is the man and which is the woman. He knows them by labels X and Y, and at the end of the game he says either "X is A and Y is B" or "X is B and Y is A." The interrogator is allowed to put questions to A and B. We now ask the question, "What will happen when a machine takes the part of A in this game?" Will the interrogator decide wrongly as often when the game is played like this as he does when the game is played between a man and a woman? These questions replace our original, "Can machines think?". (shrink)

The relationship of part to whole is one of the most fundamental there is; this is the first and only full-length study of this concept. This book shows that mereology, the formal theory of part and whole, is essential to ontology. Peter Simons surveys and criticizes previous theories, especially the standard extensional view, and proposes a more adequate account which encompasses both temporal and modal considerations in detail. 'Parts could easily be the standard book on mereology for the next twenty (...) or thirty years.' Timothy Williamson, Grazer Philosophische Studien. (shrink)

One of our great behavioral scientists, the bestselling author of Behave, plumbs the depths of the science and philosophy of decision-making to mount a devastating case against free will, an argument with profound consequences Robert Sapolsky's Behave, his now classic account of why humans do good and why they do bad, pointed toward an unsettling conclusion: We may not grasp the precise marriage of nature and nurture that creates the physics and chemistry at the base of human behavior, but that (...) doesn't mean it doesn't exist. Now, in Determined, Sapolsky takes his argument all the way, mounting a brilliant (and in his inimitable way, delightful) full-frontal assault on the pleasant fantasy that there is some separate self telling our biology what to do. Determined offers a marvelous synthesis of what we know about how consciousness works-the tight weave between reason and emotion and between stimulus and response in the moment and over a life. One by one, Sapolsky tackles all the major arguments for free will and takes them out, cutting a path through the thickets of chaos and complexity science and quantum physics, as well as touching ground on some of the wilder shores of philosophy. He shows us that the history of medicine is in no small part the history of learning that fewer and fewer things are somebody's "fault"; for example, for centuries we thought seizures were a sign of demonic possession. Yet, as he acknowledges, it's very hard, and at times impossible, to uncouple from our zeal to judge others and to judge ourselves. Sapolsky applies the new understanding of life beyond free will to some of our most essential questions around punishment, morality, and living well together. By the end, Sapolsky argues that while living our daily lives recognizing that we have no free will is going to be monumentally difficult, doing so is not going to result in anarchy, pointlessness, and existential malaise. Instead, it will make for a much more humane world. (shrink)

The paper is a response to recent criticisms of agatheism, a new pluralistic interpretation of religious belief put forward by Janusz Salamon with the aim of accommodating the epistemological challenge of religious diversity. Agatheism is an axiologically grounded religious belief which identifies God, the Absolute or the ultimate reality religiously conceived with the ultimate good as the ultimate end of all human agency and thus an explanation of its irreducibly teleological character and a source of its meaning. Janusz (...) class='Hi'>Salamon argues that this grounding of religious belief in the human axiological consciousness makes it immune to falsification by any future science. Replying to the concerns of the critics about about irrationality of doxastic commitment to a particular religious tradition, Janusz Salamon argues that to the extent the fundamental agatheistic religious belief is presupposed in such tradition as its doxastic core, its belief system - if internally coherent and aligned with a worldview that is consistent with undisputed scientific findings - may be considered rational, despite there being a plurality of such belief systems. (shrink)

At the beginning of his Metaphysics, Aristotle attributed several strange-sounding theses to Plato. Generations of Plato scholars have assumed that these could not be found in the dialogues. In heated arguments, they have debated the significance of these claims, some arguing that they constituted an 'unwritten teaching' and others maintaining that Aristotle was mistaken in attributing them to Plato. In a prior book-length study on Plato's late ontology, Kenneth M. Sayre demonstrated that, despite differences in terminology, these claims correspond to (...) themes developed by Plato in the Parmenides and the Philebus. In this book, he shows how this correspondence can be extended to key, but previously obscure, passages in the Statesman. He also examines the interpretative consequences for other sections of that dialogue, particularly those concerned with the practice of dialectical inquiry. (shrink)

This article argues that the existence of horrendous evil calls into question not just the plausibility of the most popular theodicies on offer, notably sceptical theism, but the coherence of any agatheology–that is, any theology which identifies God or the ultimate reality with the ultimate good or with a maximally good being. The article contends that the only way an agatheologian can ‘save the face of God’ after Auschwitz and Kolyma is by endorsing a non-interventionist interpretation of the Divine providence (...) which will amount to naturalisation of the discourse on evil by localising entirely in nature the causes of evil and the possible ways of its prevention. ‘Theodicy of justice as fairness’ is then presented as consistent with such naturalistic account of evils and yet compatible with a religious worldview. It justifies the Divine non-intervention by suggesting that it would not be just or fair for God to intervene on only some occasions to avert evil, if God is apparently prevented from intervening in all such cases. Since for Agatheos it is metaphysically impossible to do what is unjust or unfair, God never intervenes to avert evil. (shrink)

This collection addresses a post-WWII shift in the hierarchy of scientific explanations, where the highest goal moves from reductionism towards some ...

This book argues that Plato's Charmides presents a unitary but incomplete argument intended to lead its readers to substantive philosophical insights.

The third volume of the _Adagia_ (Proverbs) of the Amsterdam edition of the Latin texts of Erasmus gives an introduction in German and a critical edition of the Latin text of the first half of the second thousand _Adages_.

In this interview, Judith Butler remembers her teacher, the phenomenologist Maurice Natanson. Natanson observed that learning how to see is central to both teaching and learning, and Professor Butler reflects on Natanson’s views of the relation between perception, pedagogy, and world-making. She discusses the possibilities and limits of phenomenology, and its engagements with intentionality, reason, and faith. Professor Butler also reflects on the influence of phenomenology on her theory of gender performativity as well as her recent work on bodies in (...) alliance. (shrink)

In this interview, Judith Butler remembers her teacher, the phenomenologist Maurice Natanson. Natanson observed that learning how to see is central to both teaching and learning, and Professor Butler reflects on Natanson’s views of the relation between perception, pedagogy, and world-making. She discusses the possibilities and limits of phenomenology, and its engagements with intentionality, reason, and faith. Professor Butler also reflects on the influence of phenomenology on her theory of gender performativity as well as her recent work on bodies in (...) alliance. (shrink)