Zygotic gene activation (ZGA) is the critical event that governs the transition from maternal to embryonic control of development. In the mouse, ZGA occurs during the 2‐cell stage and appears to be regulated by the time following fertilization, i.e. a zygotic clock, rather than by progression through the first cell cycle. The onset of ZGA must depend on maternally inherited proteins, and post‐translational modification of these maternally derived proteins is likely to play a role in ZGA. Consistent with this prediction (...) is that protein phosphorylation catalyzed by the cAMP‐dependent protein kinase is involved in ZGA and that protein synthesis is not required for ZGA. Recent results suggest that ZGA may occur earlier than previously thought, i.e. not during the 2‐cell stage, but rather in G2 of the 1‐cell embryo. Thus ZGA may comprise a period of minor gene activation in the 1‐cell embryo that is followed by a period of major gene activation in the 2‐cell embryo. Following ZGA, the expression of constitutively activated genes may require an enhancer. (shrink)

The ovarian reserve defines female reproductive lifespan, which in humans spans decades. The ovarian reserve consists of oocytes residing in primordial follicles arrested in meiotic prophase I and is maintained independent of DNA replication and cell proliferation, thereby lacking stem cell‐based maintenance. Largely unknown is how cellular states of the ovarian reserve are established and maintained for decades. Our recent study revealed that a distinct chromatin state is established during ovarian reserve formation in mice, uncovering a novel window of epigenetic (...) programming in female germline development. We showed that an epigenetic regulator, Polycomb Repressive Complex 1 (PRC1), establishes a repressive chromatin state in perinatal mouse oocytes that is essential for prophase I‐arrested oocytes to form the ovarian reserve. Here we discuss the biological roles and mechanisms underlying epigenetic programming in ovarian reserve formation, highlighting current knowledge gaps and emerging research areas in female reproductive biology. (shrink)

The present study seeks to lay out the most basic elements of the ontology of classical Aš‘arite theology. In several cases this requires a careful examination of the traditional and the formal lexicography of certain key expressions. The topics primarily treated are: how they understood “Being/ existence” and “being/existent” and essential natures; the systematic exploitation of the equivocities of certain expressions within a general context in which other than words there are no universals proves to be elegant as well as (...) insightful; the basic categories of primary entities: independant beings and nonindependant beings, created and uncreated, the equivocity of “being/existent” as predicated of contingent entities on the one hand and of God and His attributes on the other, and certain problems that arise because of the rigid application of the system's underlying analytic principles. Nous essayons ici de presenter les éléments fondamentaux de l'ontologie de l'aš‘arisme classique. Pour quelques expressions, il a fallu examiner la lexicographie et ordinaire et technique pour bien comprendre leur emploi et leur signification. Les sujets examinés sont: le sens de “Etre/existence” et de “être/existant” et le concept de réalité essentielle; l'emploi nuancé des équivocités de quelques expressions dans un contexte où les seuls universaux sont des mots, emploi qui se révèle philosophiquement élégant; les catégories fondamentales des êtres: êtres indépendants et êtres non-indépendants, soit créés soit incréés, l'équivocité de “être/existant” dit des êtres contingents d'une part, de Dieu et ses attributs d'autre part, et enfin quelques difficultiés qui résultent de l'application rigide des principes analytiques du système. (shrink)

Richard M Weaver, a thinker and writer celebrated for his unsparing diagnoses and realistic remedies for the ills of our age, is known largely through a few of his works that remain in print. This new collection of Weaver's shorter writings, assembled by Ted J Smith III, Weaver's leading biographer, presents many long-out-of-print and never-before-published works that give new range and depth to Weaver's sweeping thought. Included are eleven previously unpublished essays and speeches that were left in near-final form (...) at the time of Weaver's death in 1963. In all, there are some one hundred and twenty-six essays, speeches, book reviews, and editorials. (shrink)

Ethics and the Clinical Encounter explores the moral dimensions of clinical medicine and the phenomenon of illness, to determine what ethics must be in order to be fully responsive to clinical encounters. Written in a lively and conversational style with minimal technical terminology, and enhanced by actual experience or real clinical situations, this volume lays out a clinical ethics methodology both in practical and theoretical terms. Here's what the experts had to say: Professor Zaner has provided us with a remarkably (...) lucid and trenchant discussion of the interface of philosophy and the field of medicine. He brings into play an extraordinary range of historial knowledge, extensive observations based on firsthand experience with medical practices, and an acute sense of philosophical argumentation. This is a work that will be an exemplary and indispensable text in the philosophy of medicine for years to come. -- Calvin Schrag... it is a highly original contribution usable in a number of fields.... It really has no competition.... The genius of Zaner's approach is to ground ethics from the 'bottom up' and to direct us to the concrete particulars of therapeutic encounters wherein lie moral and ethical matters... meaty, challenging, and ultimately rewarding.... -- Paul R. Dokecki Richard M. Zaner founded the Center for Clinical and Research Ethics at Vanderbilt University Medical Center. Having established Vanderbilt's first Hospital Ethics Committee (1985), he served as co-chair of VUMC's Ethics Committee since its inception in 1990. Zaner has published five original books, edited ten, and translated four more, and has published more than 100 sections of books and professional journals. (shrink)

Our intention here is to present the essential character of classical, sunnī kalām within a strictly formal perspective and to set out its basic aspects. It was conceived by the mutakallimīn as a rational, conceptual, and critical science and, although kalām differed in a number of basic concepts and constructs and in its analytic system, the topical organisation of the major compendia parallels that of metaphysics as understood in the contemporary Aristotelian tradition. The debates between kalām and falsafa need to (...) be examined within this context. Kalām, however, is theological in the strict sense of the term and it is as such that its problematic and its procedures are primarily to be understood. Thus seen, the object of kalām is to rationalise the cognitive content presented to Believers in the symbolic language of the koranic revelation. It has, then, four principal tasks, sc, to conceptualise, to order, to explain, and where possible to justify the primary doctrines of the community whose belief is held to be normative. Within this framework the differences that characterise the major schools as such and the various tendencies of individual masters within each school may readily be brought to light. On se propose ici de présenter, d'un point de vue strictement formel, la nature du kālam classique sunnite et d'identifier ses caractéristiques principales. II avait été conçu par les mutakallimin comme une science rationelle, conceptuelle et critique. L'organisation des matières dans ses traités reprend celle de la métaphysique dans la tradition aristotélicienne de l'époque, bien que le kalām s'en distingue par plusieurs de ses structures et concepts fondamentaux, ainsi que par son système analytique. C'est dans ce contexte qu'il faut considérer les debats qui s'instaurèrent entre kalām et falsafa. Le kalām, cependant, est d'ordre strictement théologique et c'est principalement dans ce cadre qu'il faut comprendre sa problématique et ses procédures. Le kalām a pour fonction de rationaliser le contenu cognitif offert aux croyants dans le langage symbolique de la révélation coranique. Il en résulte quatre tâches principales; il s'agit de conceptualiser, ordonner, expliquer et, dans le mesure du possible, justifier les doctrines principales reconnues par la communauté faisant référence en matière de croyance. Dans ce cadre, il sera possible de mettre en lumière les différences entre les principales écoles, ainsi que les tendances qui distinguent certains de leurs grands maîtres respectifs. (shrink)

The measurement of sensory intensity has had a long history, attracting the attention of investigators from many disciplines including physiology, psychology, physics, mathematics, philosophy, and even chemistry. While there has been a continuing doubt by some that sensation has the properties necessary for measurement, experiments designed to obtain estimates of sensory intensity have found that a general rule applies: Equal stimulus ratios produce equal sensory ratios. Theories concerning the basis for this simple psychophysical rule are discussed, with emphasis given to (...) the physical correlate theory, which considers judgments of subjective magnitudes to be based upon estimates of physical dimensions that vary regularly with changes in degree of stimulation. For the most thoroughly investigated sensory scales, brightness and loudness, the physical correlate is considered to be distance. Our “tacit knowledge” of the sensory effects of changing distance plays an essential role in matching motor activities to environmental conditions and in ensuring accurate perceptual evaluations through brightness and loudness constancies. In psychophysical experiments, subjects apparently use this same tacit knowledge when required to estimate relative subjective magnitudes. The evidence related to the physical correlate theory is summarized, and it is concluded that, while under appropriate conditions we demonstrate considerable skill in evaluating environmental relationships, we are quite unable to estimate the neurophysiological nature or quantity of sensory response. A psychophysics devoted to studying conditions required for accuracy and conditions producing errors in the perception of environmental relationships would seem to be more valuable than one devoted to subjective magnitudes. (shrink)

In this volume, fourteen scholars, many of them contemporaries of Professor Frank, engage with his legacy with important and seminal works which take some of ...

Tested the 2-process theory of detection, search, and attention presented by the current authors in a series of experiments. The studies demonstrate the qualitative difference between 2 modes of information processing: automatic detection and controlled search; trace the course of the learning of automatic detection, of categories, and of automatic-attention responses; and show the dependence of automatic detection on attending responses and demonstrate how such responses interrupt controlled processing and interfere with the focusing of attention. The learning of categories is (...) shown to improve controlled search performance. A general framework for human information processing is proposed. The framework emphasizes the roles of automatic and controlled processing. The theory is compared to and contrasted with extant models of search and attention. (shrink)

This book offers a powerful interpretation of the philosophy of William James. It focuses on the multiple directions in which James's philosophy moves and the inevitable contradictions that arise as a result. The first part of the book explores a range of James's doctrines in which he refuses to privilege any particular perspective: ethics, belief, free will, truth and meaning. The second part of the book turns to those doctrines where James privileges the perspective of mystical experience. Richard Gale (...) then shows how the relativistic tendencies can be reconciled with James's account of mystical experience. An appendix considers the distorted picture of James's philosophy that has been refracted down to us through the interpretations of his work by John Dewey. (shrink)

There has been in recent years a plethora of defenses of theism from analytical philosophers such as Plantinga, Swinburne, and Alston. Richard Gale's important book is a critical response to these writings. New versions of cosmological, ontological, and religious experience arguments are critically evaluated, along with pragmatic arguments to justify faith on the grounds of its prudential or moral benefits. A special feature of the book is the discussion of the atheological argument that attempts to deduce a contradiction from (...) the theist's way of conceiving of God's nature. In considering arguments for and against the existence of God, Gale is able to clarify many important philosophical concepts including exploration, time, free will, personhood, actuality, and the objectivity of experience. (shrink)

Early in the first volume of his Ideen zu einer reinen Phiinomeno logie und phiinomenologischen Philosophie, Edmund Husserl stated concisely the significance and scope of the problem with which this present study is concerned. When we reflect on how it is that consciousness, which is itself absolute in relation to the world, can yet take on the character of transcendence, how it can become mundanized, We see straightaway that it can do that only by means of a certain participation in (...) transcendence in the first, originary sense, which is manifestly the transcendence of material Nature. Only by means of the experiential relation to the animate organism does consciousness become really human and animal (tierischen), and only thereby does it achieve a place in the space and in the time of Nature. l Consciousness can become "worldly" only by being embodied within the world as part of it. In so far as the world is material Nature, consciousness must partake of the transcendence of material Nature. That is to say, its transcendence is manifestly an embodiment in a material, corporeal body. Consciousness, thus, takes on the characteristic of being "here and now" (ecceity) by means of experiential (or, more accurately, its intentive) relation to that corporeal being which embodies it. Accordingly, that there is a world for consciousness is a conse quence in the first instance of its embodiment by 2 that corporeal body which is for it its own animate organism. (shrink)

Early in the first volume of his Ideen zu einer reinen Phiinomeno logie und phiinomenologischen Philosophie, Edmund Husserl stated concisely the significance and scope of the problem with which this present study is concerned. When we reflect on how it is that consciousness, which is itself absolute in relation to the world, can yet take on the character of transcendence, how it can become mundanized, We see straightaway that it can do that only by means of a certain participation in (...) transcendence in the first, originary sense, which is manifestly the transcendence of material Nature. Only by means of the experiential relation to the animate organism does consciousness become really human and animal (tierischen), and only thereby does it achieve a place in the space and in the time of Nature. l Consciousness can become "worldly" only by being embodied within the world as part of it. In so far as the world is material Nature, consciousness must partake of the transcendence of material Nature. That is to say, its transcendence is manifestly an embodiment in a material, corporeal body. Consciousness, thus, takes on the characteristic of being "here and now" (ecceity) by means of experiential (or, more accurately, its intentive) relation to that corporeal being which embodies it. Accordingly, that there is a world for consciousness is a conse quence in the first instance of its embodiment by 2 that corporeal body which is for it its own animate organism. (shrink)

History of science, it has been argued, has benefited philosophers of science primarily by forcing them into greater contact with "real science." In this paper I argue that additional major benefits arise from the importance of specifically historical considerations within philosophy of science. Loci for specifically historical investigations include: (1) making and evaluating rational reconstructions of particular theories and explanations, (2) estimating the degree of support earned by particular theories and theoretical claims, and (3) evaluating proposed philosophical norms for the (...) evaluation of the degree of support for theories and the worth of explanations. More generally, I argue that theories develop and change structure with time, that (like biological species) they are historical entities. Accordingly, both the identification and the evaluation of theories are essentially historical in character. (shrink)

It is argued here that business firms can and do provide an incubator that enables the Aristotelian category of friendships of advantage to develop into friendships of virtue. This contradicts other literature that views acquaintances of utility as the business norm, and expresses pessimism concerning more advanced virtuous development of friendship within the business firm. It is argued here, however, that this virtuous development is integral to the Kantian social aim of pursuing a moral community, an aim which declares the (...) appropriate moral motivation for business, and that certainly should incorporate a role for developing virtuous relations as a component of that pursuit. An atmosphere that encourages the development of relations of virtue is feasible, exists in real business, and is optimal for pursuit of moral business communities. (shrink)

This honest, forthright, and beautifully-written book introduces readers to the human variations on medical topics spoken of in abstract in the daily news--euthanasia, assisted suicide, abortion, "extreme procedures", genetic testing, experimental surgeries--and to the people who must agonize over those decisions regarding themselves and their loved ones.

This article reviews current methods for evaluating models in the cognitive sciences, including theoretically based approaches, such as Bayes factors and minimum description length measures; simulation approaches, including model mimicry evaluations; and practical approaches, such as validation and generalization measures. This article argues that, although often useful in specific settings, most of these approaches are limited in their ability to give a general assessment of models. This article argues that hierarchical methods, generally, and hierarchical Bayesian methods, specifically, can provide a (...) more thorough evaluation of models in the cognitive sciences. This article presents two worked examples of hierarchical Bayesian analyses to demonstrate how the approach addresses key questions of descriptive adequacy, parameter interference, prediction, and generalization in principled and coherent ways. (shrink)

This paper is devoted to an examination of the discovery, characterization, and analysis of the functions of microRNAs, which also serves as a vehicle for demonstrating the importance of exploratory experimentation in current (post-genomic) molecular biology. The material on microRNAs is important in its own right: it provides important insight into the extreme complexity of regulatory networks involving components made of DNA, RNA, and protein. These networks play a central role in regulating development of multicellular organisms and illustrate the importance (...) of epigenetic as well as genetic systems in evolution and development. The examination of these matters yields principled arguments for the historicity of the functions of key biological molecules and for the indispensability of exploratory experimentation in contemporary molecular biology as well as some insight into the complex interplay between exploratory experimentation and hypothesis-driven science. This latter result is not only important for philosophy of science, but also of practical importance for the evaluation of grant proposals, although the elaboration of this latter claim must be left for another occasion. (shrink)

In what has become a classic work, Richard M. Weaver unsparingly diagnoses the ills of our age and offers a realistic remedy. He asserts that the world is intelligible, and that man is free. The catastrophes of our age are the product not of necessity but of unintelligent choice. A cure, he submits, is possible. It lies in the right use of man's reason, in the renewed acceptance of an absolute reality, and in the recognition that ideas—like actions—have consequences.

This book offers students a philosophical introduction to the ethical foundations of business management. It combines lessons from Kant with virtue ethics and also touches upon additional approaches such as utilitarianism. At the core of the book lies the concept of the nexus of imperfect managerial duty: building and reinforcing the virtuous managerial team, engaging in reasoned discourse among all stakeholders, and diligently pursuing business responsibilities, including the creative efforts necessary for modern organizations. Case illustrations of these applications are presented (...) throughout the book, including chapter appendices. Ancillary videos, test and answer banks and sample syllabi are available online via the author’s website. (shrink)

The aim of this paper will be to try and show why there could not be any acceptable counter-stipulation-example to this analytic truth. The overall strategy will be to articulate the conceptual centrality of this analytic truth by showing that a change in it will cause absurdities to break out in certain neighboring concepts with which the concept of cause has logical liaisons, such as action, possibility, intention, deliberation, memory, responsibility, and punishment: and when we try to protect ourselves from (...) these absurdities by altering these latter concepts as well, we will have twisted our concept of causality, along with these other concepts, out of recognition. In other words, it will be argued that to give up this analytic truth will require such a drastic overhauling of the basic concepts of our conceptual system that they will not be a recognizable analog of their former self. Obviously, I cannot give any precise criterion for just when an altered concept ceases to be a permissible analog of its former self. While there is room for disagreement about these matters, we can reach agreement upon the logical connections between the concept of causality and these other neighboring concepts, so that we can determine what changes must be made in the latter so as to accommodate a change in the former. Whether we then wish to say that these changes are so extensive that these concepts are not permissible analogs of their former selves is of secondary importance. However, I do believe that it can be shown that the extended concept of causality which permits a cause to be later than its effect requires such a drastic change in neighboring concepts that there will be little room for disagreement as to whether it is a legitimate analog to the original concept of causality. (shrink)

In what sense does time exist? Is it an objective feature of the external world? Or is its real nature dependent on the way man experiences it? Has modern science brought us closer to the answer to St. Augustine's exasperated outcry, 'What, then, is time?' ? Ever since Aristotle, thinkers have been struggling with this most confounding and elusive of philosophical questions. How long does the present moment last? Can we make statements about the future that are clearly true or (...) clearly false? And if so, must we be fatalists? This volume presents twenty-three discussions of the problem of time. A section on classical and modern attempts at definition is followed by four groups of essays drawn largely from contemporary philosophy, each preface with an introduction by the editor. First, in a chapter entitled 'The Static versus the Dynamic Temporal', four philosophers advance solutions to McTaggart's famous proof of time's unreality. In the next two sections, the discussion turns to the meaning of the 'open future' and to the much-debated nature of 'human time'. Finally, modern science and philosophy tackle Zeno's celebrated paradoxes. The essays by Adolf Grnbaum, Nicholas Rescher, and William Barrett are published for the first time in this volume. (shrink)

Our paper ‘A new cosmological argument’ gave an argument for the existence of God making use of the weak Principle of Sufficient Reason (W-PSR) which states that for every proposition p, if p is true, then it is possible that there is an explanation for p. Recently, Graham Oppy, as well as Kevin Davey and Rob Clifton, have criticized the argument. We reply to these criticisms. The most interesting kind of criticism in both papers alleges that the W-PSR can be (...) justifiably denied by the atheist, and constitutes no improvement on the strong Principle of Sufficient Reason (S-PSR) which claims that every true proposition in fact has an explanation. The criticism is predicated on the fact that it can be shown that the W-PSR entails the S-PSR. We argue that the W-PSR's plausibility remains despite the criticisms. From this it can be seen to follow that the entailment relation between the W-PSR and the S-PSR gives one reason to believe the S-PSR. (shrink)

Quilts with "a black-and-white checked" pattern "for the NASCAR market" are stitched together by an Amish woman whose family uses an outdoor privy because church rules stipulate "no indoor plumbing"; an Amish man delivers cans of his milk to an Amish-owned neighborhood collection tank cooled by electricity because state laws require the refrigeration of milk. These are just a few of the images Karen Johnson-Weiner presents of the New York State Amish and their continuing effort to maintain a life disconnected (...) from the surrounding society upon which they are, to varying degrees, economically dependent. The Amish's struggle to preserve separate-from-the world communities and the diversity among the various Amish... (shrink)