Cell cycle dynamics has emerged as a key regulator of stem cell fate decisions. In particular, differentiation decisions are associated with the G1 phase, and recent evidence suggests that self‐renewal is actively regulated outside of G1. The mechanisms underlying these phenomena are largely unknown, but direct control of gene regulatory programs by the cell cycle machinery is heavily implicated. A recent study sheds important mechanistic insight by demonstrating that in human embryonic stem cells (hESCs) the Cyclin‐dependent kinase CDK2 controls a (...) wide‐spread epigenetic program that drives transcription at differentiation‐related gene promoters specifically in G1. Here, we discuss this finding and explore whether similar mechanisms are likely to function in multipotent stem cells. The implications of this discovery toward our understanding of stem cell‐related disease are discussed, and we postulate novel mechanisms that position the cell cycle as a regulator of cell fate gene networks at epigenetic, transcriptional and post‐transcriptional levels. (shrink)

(i) Scientific realism is primarily a metaphysical doctrine about the existence and nature of the unobservables of science. (ii) There are good explanationist arguments for realism, most famously that from the success of science, provided abduction is allowed. Abduction seems to be on an equal footing, at least, with other ampliative methods of inference. (iii) We have no reason to believe a doctrine of empirical equivalence that would sustain the underdetermination argument against realism. (iv) The key to defending realism from (...) the pessimistic meta-induction is that we have greatly improved our capacity to understand the unobservable world over recent centuries. (shrink)

In the early 1920s, the German mathematician David Hilbert (1862–1943) put forward a new proposal for the foundation of classical mathematics which has come to be known as Hilbert's Program. It calls for a formalization of all of mathematics in axiomatic form, together with a proof that this axiomatization of mathematics is consistent. The consistency proof itself was to be carried out using only what Hilbert called “finitary” methods. The special epistemological character of finitary reasoning then yields the required justification (...) of classical mathematics. Although Hilbert proposed his program in this form only in 1921, various facets of it are rooted in foundational work of his going back until around 1900, when he first pointed out the necessity of giving a direct consistency proof of analysis. Work on the program progressed significantly in the 1920s with contributions from logicians such as Paul Bernays, Wilhelm Ackermann, John von Neumann, and Jacques Herbrand. It was also a great influence on Kurt Gödel, whose work on the incompleteness theorems were motivated by Hilbert's Program. Gödel's work is generally taken to show that Hilbert's Program cannot be carried out. It has nevertheless continued to be an influential position in the philosophy of mathematics, and, starting with the work of Gerhard Gentzen in the 1930s, work on so-called Relativized Hilbert Programs have been central to the development of proof theory. (shrink)

(This is for the series Elements of Decision Theory published by Cambridge University Press and edited by Martin Peterson) -/- Our beliefs come in degrees. I believe some things more strongly than I believe others. I believe very strongly that global temperatures will continue to rise during the coming century; I believe slightly less strongly that the European Union will still exist in 2029; and I believe much less strongly that Cardiff is east of Edinburgh. My credence in something is (...) a measure of the strength of my belief in it; it represents my level of confidence in it. These are the states of mind we report when we say things like ‘I’m 20% confident I switch off the gas before I left' or ‘I’m 99.9% confident that it is raining outside'. -/- There are laws that govern these credences. For instance, I shouldn't be more confident that sea levels will rise by over 2 metres in the next 100 years than I am that they'll rise by over 1 metre, since the latter is true if the former is. This book is about a particular way we might try to establish these laws of credence: the Dutch Book arguments (For briefer overviews of these arguments, see Alan Hájek’s entry in the Oxford Handbook of Rational and Social Choice and Susan Vineberg’s entry in the Stanford Encyclopaedia.) -/- We begin, in Chapter 2, with the standard formulation of the various Dutch Book arguments that we'll consider: arguments for Probabilism, Countable Additivity, Regularity, and the Principal Principle. In Chapter 3, we subject this standard formulation to rigorous stress-testing, and make some small adjustments so that it can withstand various objections. What we are left with is still recognisably the orthodox Dutch Book argument. In Chapter 4, we set out the Dutch Strategy argument for Conditionalization. In Chapters 5 and 6, we consider two objections to Dutch Book arguments that cannot be addressed by making small adjustments. Instead, we must completely redesign those arguments, replacing them with ones that share a general approach but few specific details. In Chapter 7, we consider a further objection to which I do not have a response. In Chapter 8, we'll ask what happens to the Dutch Book arguments if we change certain features of the basic framework in which we've been working: first, we ask how Dutch Book arguments fare when we consider credences in self-locating propositions, such as It is Monday; second, we lift the assumption that the background logic is classical and explore Dutch Book arguments for non-classical logics; third, we lift the assumption that an agent's credal state can be represented by a single assignment of numerical values to the propositions she considers. In Chapter 9, we present the mathematical results that underpin these arguments. (shrink)

Aristotle conceives of ethical theory as a field distinct from the theoretical sciences. Its methodology must match its subject matter—good action—and must respect the fact that in this field many generalizations hold only for the most part. We study ethics in order to improve our lives, and therefore its principal concern is the nature of human well-being. Aristotle follows Socrates and Plato in taking the virtues to be central to a well-lived life. Like Plato, he regards the ethical virtues (justice, (...) courage, temperance and so on) as complex rational, emotional and social skills. But he rejects Plato's idea that a training in the sciences and metaphysics is a necessary prerequisite for a full understanding of our good. What we need, in order to live well, is a proper appreciation of the way in which such goods as friendship, pleasure, virtue, honor and wealth fit together as a whole. In order to apply that general understanding to particular cases, we must acquire, through proper upbringing and habits, the ability to see, on each occasion, which course of action is best supported by reasons. Therefore practical wisdom, as he conceives it, cannot be acquired solely by learning general rules. We must also acquire, through practice, those deliberative, emotional, and social skills that enable us to put our general understanding of well-being into practice in ways that are suitable to each occasion. (shrink)

The distinction between phenotype and genotype is fundamental to the understanding of heredity and development of organisms. The genotype of an organism is the class to which that organism belongs as determined by the description of the actual physical material made up of DNA that was passed to the organism by its parents at the organism's conception. For sexually reproducing organisms that physical material consists of the DNA contributed to the fertilized egg by the sperm and egg of its two (...) parents. For asexually reproducing organisms, for example bacteria, the inherited material is a direct copy of the DNA of its parent. The phenotype of an organism is the class to which that organism belongs as determined by the description of the physical and behavioral characteristics of the organism, for example its size and shape, its metabolic activities and its pattern of movement. (shrink)

It has sometimes been suggested that quantum phenomena exhibit a characteristic holism or nonseparability, and that this distinguishes quantum from classical physics. One puzzling quantum phenomenon arises when one performs measurements of spin or polarization on certain separated quantum systems. The results of these measurements exhibit patterns of statistical correlation that resist traditional causal explanation. Some have held that it is possible to understand these patterns as instances or consequences of quantum holism or nonseparability. Just what holism and nonseparability are (...) supposed to be has not always been made clear, though, and each of these notions has been understood in different ways. Moreover, while some have taken holism and nonseparability to come to the same thing, others have thought it important to distinguish the two. Any evaluation of the significance of quantum holism and/or nonseparability must rest on a careful analysis of these notions. (shrink)

The epsilon calculus is a logical formalism developed by David Hilbert in the service of his program in the foundations of mathematics. The epsilon operator is a term-forming operator which replaces quantifiers in ordinary predicate logic. Specifically, in the calculus, a term εx A denotes some x satisfying A(x), if there is one. In Hilbert's Program, the epsilon terms play the role of ideal elements; the aim of Hilbert's finitistic consistency proofs is to give a procedure which removes such terms (...) from a formal proof. The procedures by which this is to be carried out are based on Hilbert's epsilon substitution method. The epsilon calculus, however, has applications in other contexts as well. The first general application of the epsilon calculus was in Hilbert's epsilon theorems, which in turn provide the basis for the first correct proof of Herbrand's theorem. More recently, variants of the epsilon operator have been applied in linguistics and linguistic philosophy to deal with anaphoric pronouns. (shrink)

The Madhyamaka school of Buddhism, the followers of which are called Mādhyamikas, was one of the two principal schools of Mahāyāna Buddhism in India, the other school being the Yogācāra. The name of the school is a reference to the claim made of Buddhism in general that it is a middle path (madhyamā pratipad) that avoids the two extremes of eternalism—the doctrine that all things exist because of an eternal essence—and annihilationism—the doctrine that things have essences while they exist but (...) that these essences are annihilated just when the things themselves go out of existence. The conviction of the Madhyamaka school, which can be called the Centrist school in English, is that this middle path is best achieved by a denial that things have any inherent natures at all. All things are, in other words, empty of inherent natures. This doctrine of universal emptiness of inherent natures (svabhāva-śūnyatā) is the hallmark of the school, which places the school solidly in the tradition associated with the Perfection of Wisdom (prajñāpāramitā) literature of Mahāyāna Buddhism. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:EDWARD W. STRONG, 1901--1990 Edward W. Strong, one.of the founders and leaders of the Journal of the HistoryofPhilosophy,passed away on January 13, 199o, after a long struggle with cancer. Born in Dallas, Oregon in 19~ 1, he was eighty-eight years old when he died. He did his undergraduate studies at Stanford, receiving his B.A. in 1925. Then he went on to graduate studies at Columbia, where he received (...) a master's degree in 1927 and a Ph.D. in 1937. He taught at City College in New York from 1927 to 1932, and then began his long career at the University of California, Berkeley, where he remained for the rest of his academic life. During World War II, he became laboratory manager of the university's Radiation Laboratory (now called the Lawrence Berkeley Laboratory), which was part of the Manhattan Project to develop the atomic bomb. After the war, Strong became a full professor in 1947, chairman of the Sociology Department from 1946 to 1952, Associate Dean of the College of Letters and Sciences from 1947 to 1955, a leader of the Academic Senate and its Educational Policy Committee, and Chancellor of the Berkeley campus from 1961 to 1965.This was a period of very rapid growth for the campus as well as its most troubled time. When the student rebellion--the Free Speech Movement--broke out, Strong tried valiantly but unsuccessfully to preserve those academic values he felt most challenged. As the conflict wore on, he ceased to have the full support of his superiors, the President of the Universityand the Board of Regents, who negotiated a resolution with the students, the effects of which are still being felt at Berkeley and elsewhere in the United States. Some feel that Strong's position in the struggle that transformed American universities has not been properly understood, and that his role has been portrayed unfairly to enhance that of his superiors. In any event, he resigned as Chancellor and became Professor Emeritus in 1967. Strong developed his interest in the history of philosophy, history of science, and history of ideas at Columbia during its heyday as a center for such concerns, under the leadership of John Dewey and Frederick Woodbridge. He told me that he was also very much influenced by the historical interests of Morris Raphael Cohen, his senior colleague at City College. His dissertation, Proceduresand Methods,was, and still is, a basic study of the origin and development of modern science. (It was mentioned approvingly in an article by Ernst [9] 10 JOURNAL OF THE HISTORY OF PHILOSOPHY 29:1 JANUARY 1991 Cassirer, in 194o). In contrast to E. A. Burtt, whose MetaphysicalFoundationsof ModernPhysicalSciencestressed the philosophical and theological concerns of the early scientists, Strong emphasized the practical engineering concerns that were involved at the time. This led him to studies of Kepler, Galileo, and Newton, as well as to the scientific views of medieval thinkers, and modern views in the philosophy of science. Philosophically he was a naturalist, continuing the Columbia tradition. He was also very interested in Bergson's views, especially as they related to modern scientific ideas. He was the inspirer and founder of the History of Science discussion group at Berkeley, which became an important forum for creative research in this area. Strong was President of the American Philosophical Association in 1959. Because of the limited attention and concern given to the history of philosophy in most of the then-existing philosophicaljournals in America, the American Philosophical Association in 1957 approved in principle the establishment of a journal devoted to the history of philosophy, and appointed a committee of six members--Paul Kristeller, Gregory Vlastos, Richard McKeon, Julius Weinberg, John Goheen, and Edward Strong--to explore "ways and means to this end." Since all American philosophical journals at that time were published in the East and Midwest, Strong and Goheen were encouraged to try to establish the journal in the West. Strong has detailed the efforts to do this in his article, "The Founding of theJournal oftheHistoryofPhilosophy,"Journalof theHistoryofPhilosophy~5 (1987): 179-83. I first met Ed Strong at Trinity College, Dublin, in the summer of 1953, when I was a... (shrink)

This new translation is the first to be published in a twenty-volume English-language edition of _The Complete Works of Friedrich Nietzsche_, the first complete, critical, and annotated translation of all of Nietzsche's work. The Stanford edition is based on the Colli-Montinari edition, which has received universal praise: "It has revolutionized our understanding of one of the greatest German thinkers"; "Scholars can be confident for the first time of having a trustworthy text." Under the title _Unzeitgemässe Betrachtungen_, Nietzsche collected four (...) essays published separately between 1873 and 1876: "David Strauss the Confessor and the Writer," "On the Utility and Liability of History for Life," "Schopenhauer as Educator," and "Richard Wagner in Bayreuth." The title, newly translated as _Unfashionable Observations_, spells out the common impulse linking these essays: Nietzsche's inimical attitude toward his "time," understood broadly as all the mainstream and popular movements that constituted contemporary European, but especially German, "culture" in the wake of the Prussian military victory over the French in 1871. The _Unfashionable Observations_ are foundational works for Nietzsche's entire philosophy, prefiguring both his characteristic philosophical style and many of the major ideas he would develop in his later writings. This is the first English translation to include Nietzsche's variants to the published text. (shrink)

Most models of generational succession in sexually reproducing populations necessarily move back and forth between genic and genotypic spaces. We show that transitions between and within these spaces are usually hidden by unstated assumptions about processes in these spaces. We also examine a widely endorsed claim regarding the mathematical equivalence of kin-, group-, individual-, and allelic-selection models made by Lee Dugatkin and Kern Reeve. We show that the claimed mathematical equivalence of the models does not hold. *Received January 2007; revised (...) April 2008. †To contact the authors, please write to: Elisabeth Lloyd, Department of History and Philosophy of Science, 130 Goodbody Hall, Indiana University, Bloomington, IN 47405; e-mail: [email protected]; Richard Lewontin, Department of Organismic and Evolutionary Biology, Harvard University, 26 Oxford Street, Cambridge, MA 02138; Marcus Feldman, Department of Biological Sciences, Stanford University, Stanford, CA 94305; e-mail: marc@charles.stanford.edu. (shrink)

Since their inception, the Perspectives in Logic and Lecture Notes in Logic series have published seminal works by leading logicians. Many of the original books in the series have been unavailable for years, but they are now in print once again. This volume, the fifteenth publication in the Lecture Notes in Logic series, collects papers presented at the symposium 'Reflections on the Foundations of Mathematics' held in celebration of Solomon Feferman's 70th birthday (The 'Feferfest') at Stanford University, California in (...) 1988. Feferman has shaped the field of foundational research for nearly half a century. These papers reflect his broad interests as well as his approach to foundational research, which emphasizes the solution of mathematical and philosophical problems. There are four sections, covering proof theoretic analysis, logic and computation, applicative and self-applicative theories, and philosophy of modern mathematical and logic thought. (shrink)

Time is central to Luhmann’s writings on social systems. Social systems, as systems of meaning, operate within three dimensions: factual, social and temporal. Each of these dimensions entails selections of actualities from potentialities (or contingencies) within horizons. Whilst the factual dimension involves selections based on distinguishing ‘this’ from ‘something else’, and the social distinguishes between alter and ego (asking with respect to any meaning whether another experiences it as I do), the temporal dimension operates with the primary distinction of before (...) and after. In the temporal dimension, everything is ‘ordered only according to the when and not to the who/what/where/how of experience and action’ (Luhmann in Social systems. Stanford University Press, Stanford, 1995, p. 78). In this paper, we explore the connection between the temporal dimension of meaning within the legal system and its connection to justice. We begin by setting out succinctly the role played by justice within the legal system, as presented by Luhmann, particularly in his book Law as a social system (2004). From this beginning, we move on to consider the relationship between law, justice and time, taking two examples. The first is the temporality of judicial decisions. The second concerns the relationship between the temporal meaning of law’s own operations, and the presumption of innocence. (shrink)

Over the past 50 years the diversity of higher education faculty in the mathematical, physical, computer, and engineering sciences has advanced very little at 4-year universities in the United States. This is despite laws and policies such as affirmative action, interventions by universities, and enormous financial investment by federal agencies to diversify science, technology, mathematics, and engineering career pathways into academia. Data comparing the fraction of underrepresented minority postdoctoral scholars to the fraction of faculty at these institutions offer a straightforward (...) empirical explanation for this state of affairs. URM postdoc appointments lag significantly behind progress in terms of both undergraduate and Ph.D.-level STEM student populations. Indeed, URM postdoc appointments lag well-behind faculty diversity itself in the MPCES fields, most of which draw their faculty heavily from the postdoctoral ranks, particularly at research-intensive universities. Thus, a sea-change in how postdocs are recruited, how their careers are developed, and how they are identified as potential faculty is required in order to diversify the nation’s faculty, and particularly the R1 MPCES professoriate. Our research shows that both Ph.D. students and postdocs benefit from intentional structure at various levels of their respective “apprentice” experiences, a factor that we believe has been neglected. Several key structural approaches are highly effective in these regards: A collaborative approach in which leading research universities collectively identify outstanding URM candidates; Faculty engagement in recruiting and supporting these postdocs; Inter-institutional exchange programs to heighten the visibility and broaden the professional experiences of these postdocs; Community-building activities that create a sense of belonging and encourage continuing in academia for each cohort; and Continuing research based on outcomes and new experimental approaches. The California Alliance, consisting of UC Berkeley, UCLA, Caltech, and Stanford, has been engaged in such a program for almost a decade now, with most of the California Alliance URM postdocs now in tenure track positions or on the path toward careers as faculty at research intensive institutions. If this approach was brought to scale by involving the top 25 or so URM Ph.D.-producing R1 institutions in the MPCES fields, about 40% of the national URM postdoctoral population in these fields could be affected. Although this impact would fall short of bringing URM MPCES faculty ranks up to full representation of the United States population as a whole, it would vastly improve the outlook for URM students and their aspirations to take on leadership roles as scientists and engineers. (shrink)

Kyle Stanford’s reformulation of the problem of underdetermination has the potential to highlight the epistemic obligations of scientists. Stanford, however, presents the phenomenon of unconceived alternatives as a problem for realists, despite critics’ insistence that we have contextual explanations for scientists’ failure to conceive of their successors’ theories. I propose that responsibilist epistemology and the concept of “role oughts,” as discussed by Lorraine Code and Richard Feldman, can pacify Stanford’s critics and reveal broader relevance of the (...) “new induction.” The possibility of unconceived alternatives pushes us to question our contemporary expectation for scientists to reason outside of their historical moment. (shrink)

Richard Rorty (1931–2007) developed a distinctive and controversial brand of pragmatism that expressed itself along two main axes. One is negative—a critical diagnosis of what Rorty takes to be defining projects of modern philosophy. The other is positive—an attempt to show what intellectual culture might look like, once we free ourselves from the governing metaphors of mind and knowledge in which the traditional problems of epistemology and metaphysics (and indeed, in Rorty's view, the self-conception of modern philosophy) are rooted. (...) The centerpiece of Rorty's critique is the provocative account offered in Philosophy and the Mirror of Nature (1979, hereafter PMN). In this book, and in the closely related essays collected in Consequences of Pragmatism (1982, hereafter CP), Rorty's principal target is the philosophical idea of knowledge as representation, as a mental mirroring of a mind-external world. Providing a contrasting image of philosophy, Rorty has sought to integrate and apply the milestone achievements of Dewey, Hegel and Darwin in a pragmatist synthesis of historicism and naturalism. Characterizations and illustrations of a post-epistemological intellectual culture, present in both PMN (part III) and CP (xxxvii-xliv), are more richly developed in later works, such as Contingency, Irony, and Solidarity (1989, hereafter CIS), in the popular essays and articles collected in Philosophy and Social Hope (1999), and in the four volumes of philosophical papers, Objectivity, Relativism, and Truth (1991, hereafter ORT); Essays on Heidegger and Others (1991, hereafter EHO); Truth and Progress (1998, hereafter TP); and Philosophy as Cultural Politics (2007, hereafter PCP). In these writings, ranging over an unusually wide intellectual territory, Rorty offers a highly integrated, multifaceted view of thought, culture, and politics, a view that has made him one of the most widely discussed philosophers in our time. (shrink)