Epigenetic and transcriptional variability contribute to the vast diversity of cellular and organismal phenotypes and are key in human health and disease. In this review, we describe different types, sources, and determinants of epigenetic and transcriptional variability, enabling cells and organisms to adapt and evolve to a changing environment. We highlight the latest research and hypotheses on how chromatin structure and the epigenome influence gene expression variability. Further, we provide an overview of challenges in the analysis of biological variability. An (...) improved understanding of the molecular mechanisms underlying epigenetic and transcriptional variability, at both the intra- and inter-individual level, provides great opportunity for disease prevention, better therapeutic approaches, and personalized medicine. Epigenetic and transcriptional variability mediate phenotypic plasticity, enabling adaptation to changing environments. In this review, we describe the sources of inter- and intra-individual variability and discuss epigenetic regulators of gene expression variability, including DNA methylation and chromatin structure. Understanding these molecular mechanisms will improve therapeutic approaches and personalized medicine. (shrink)

Analyses of so-called ‘post-truth’ discourse in populist politics have so far largely focussed on sorting it into cases of lying, bullshitting, bubble-like epistemic constraints, or alternative epistemic norms flouting objective truth. We review these proposals and point out problems with each. Some scholars, however, have recently drawn attention to how apparent assertions of facts in these contexts seem to be functionally entangled with expressing or affirming social identities. To get a clearer picture of what such an explanation might amount to, (...) we differentiate four different ways in which social identities might be connected to apparently assertive discourse: signalling, expressive affirmation, dissonance reduction, and identity grounding. Distinguishing and deciding among these will matter not only for providing an accurate analysis of post-truth discourse, but also for determining the exact grounds on which it merits criticism and for what might be done about it. (shrink)

Non è detto che ogni essere femminile sia una donna. Donna non si nasce, lo si diventa.Simone de Beauvoir, Il Secondo Sesso 1. Introduzione L’incredibile storia di Thomas Beatie, transessuale uomo ma con un sistema riproduttivo femminile, sembra mettere fortemente in discussione uno dei modi in cui convenzionalmente distinguiamo donne e uomini. Nato femmina, Thomas decide in età adulta di cambiare sesso e di sottoporsi a un intervento per la rimozione del seno e a una terapia ormonale. Volend...

A philosophical frame for violence against women and girls creates unique opportunities to deepen our understanding of the embodied consequences of men’s violence. Using the seemingly innocuous example of being told to “cheer up” or “smile”, we draw on Simone de Beauvoir and Franz Fanon’s work on recognition to suggest that a phenomenological approach to sexual violence may help to voice previously inarticulable harms. The dual frame of Beauvoir and Fanon also highlights the need for philosophical work on sexual (...) violence to take account of the insights of intersectionality. (shrink)

Economic change, globalisation and harmonisation of European Law have brought new challenges to contract law. The contributions in this Volume by prominent legal scholars deal with current trends and perspectives in European and International Contract Law and their impact on the various domestic legal systems. The Compendium provides an analysis of new developments in formation of contract, performance and remedies, consumer contract law and the particularly controversial area of anti-discrimination law. Experts in their field examine the underlying legal principles and (...) problems arising in legal practice in Common Law and Civil Law. The essays written in English, German and French are the product of a series of lectures held in 2006 at the Centre for European Private Law at the University of Münster, Germany. The contributing authors are: John Adams, Hugh Beale, Giuditta Cordero-Moss, Barbara Dauner-Lieb, Michele Graziadei, Thomas Gutmann, Geraint Howells, Simon James, Paul Lagarde, Matthias Lehmann, Peter Møgelvang-Hansen, Salvatore Patti, Thomas Pfeiffer, John C. Reitz, Judith Rochfeld, Martin Schmidt-Kessel, Jürgen Schmidt-Räntsch, Alessandro Somma, Stefano Troiano, Christian Twigg-Flesner, Antoni Vaquer Aloy and Fryderyk Zoll. (shrink)

Simone Weil (1909-1943) was a defining figure of the twentieth century; a philosopher, Christian, resistance fighter, anarchist, feminist, labor activist and teacher. She was described by T. S. Eliot as "a woman of genius, of a kind of genius akin to that of the saints," and by Albert Camus as "the only great spirit of our time." Originally published posthumously in two volumes, these newly reissued notebooks, are among the very few unedited personal writings of Weil's that still survive (...) today. Containing her thoughts on art, love, science, God and the meaning of life, they give context and meaning to Weil's famous works, revealing a unique philosophy in development and offering a rare private glimpse of her singular personality. (shrink)

Most epistemologists hold that knowledge entails belief. However, proponents of this claim rarely offer a positive argument in support of it. Rather, they tend to treat the view as obvious and assert that there are no convincing counterexamples. We find this strategy to be problematic. We do not find the standard view obvious, and moreover, we think there are cases in which it is intuitively plausible that a subject knows some proposition P without—or at least without determinately—believing that P. Accordingly, (...) we present five plausible examples of knowledge without (determinate) belief, and we present empirical evidence suggesting that our intuitions about these scenarios are not atypical. (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)

Particle indistinguishability has always been considered a purely quantum mechanical concept. In parallel, indistinguishable particles have been thought to be entities that are not properly speaking objects at all. I argue, to the contrary, that the concept can equally be applied to classical particles, and that in either case particles may (with certain exceptions) be counted as objects even though they are indistinguishable. The exceptions are elementary bosons (for example photons).

The desideratum of semantic interoperability has been intensively discussed in medical informatics circles in recent years. Originally, experts assumed that this issue could be sufficiently addressed by insisting simply on the application of shared clinical terminologies or clinical information models. However, the use of the term ‘ontology’ has been steadily increasing more recently. We discuss criteria for distinguishing clinical ontologies from clinical terminologies and information models. Then, we briefly present the role clinical ontologies play in two multicentric research projects. Finally, (...) we discuss the interactions between these different kinds of knowledge representation artifacts and the stakeholders involved in developing interoperational real-world clinical applications. We provide ontology engineering examples from two EU-funded projects. (shrink)

We demonstrate that the quantum-mechanical description of composite physical systems of an arbitrary number of similar fermions in all their admissible states, mixed or pure, for all finite-dimensional Hilbert spaces, is not in conflict with Leibniz's Principle of the Identity of Indiscernibles (PII). We discern the fermions by means of physically meaningful, permutation-invariant categorical relations, i.e. relations independent of the quantum-mechanical probabilities. If, indeed, probabilistic relations are permitted as well, we argue that similar bosons can also be discerned in all (...) their admissible states; but their categorical discernibility turns out to be a state-dependent matter. In all demonstrated cases of discernibility, the fermions and the bosons are discerned (i) with only minimal assumptions on the interpretation of quantum mechanics; (ii) without appealing to metaphysical notions, such as Scotusian haecceitas, Lockean substrata, Postian transcendental individuality or Adamsian primitive thisness; and (iii) without revising the general framework of classical elementary predicate logic and standard set theory, thus without revising standard mathematics. This confutes: (a) the currently dominant view that, provided (i) and (ii), the quantum-mechanical description of such composite physical systems always conflicts with PII; and (b) that if PII can be saved at all, the only way to do it is by adopting one or other of the thick metaphysical notions mentioned above. Among the most general and influential arguments for the currently dominant view are those due to Schrodinger, Margenau, Cortes, Dalla Chiara, Di Francia, Redhead, French, Teller, Butterfield, Giuntini, Mittelstaedt, Castellani, Krause and Huggett. We review them succinctly and critically as well as related arguments by van Fraassen and Massimi. (shrink)

The pivotal role of the relation part-of in the description of living organisms is widely acknowledged. Organisms are open systems, which means that in contradistinction to mechanical artifacts they are characterized by a continuous flow and exchange of matter. A closer analysis of the spatial relations in biological organisms reveals that the decision as to whether a given particular is part-of a second particular or whether it is only contained-in the second particular is often controversial. We here propose a rule-based (...) approach which allows us to decide on the basis of well-defined criteria which of the two relations holds between two anatomical objects, given that one spatially includes the other. We discuss the advantages and limitations of this approach, using concrete examples from human anatomy. (shrink)

In a time marked by the development of innovative treatments in healthcare and the need for health professionals to deal with resulting ethical dilemmas in clinical practice, this study was developed to determine the influence of the bioethics teaching on the moral competence of medical and nursing students. The authors conduct a longitudinal study using the Moral Competence Test extended version before and after attending the ethics curricular unit, in three nursing schools and three medical schools of Portugal. In this (...) questionnaire the participant is confronted with three ethical dilemmas and asked to evaluate arguments for and against the attitude of the main character. For both nursing and medical students, C-score was lower after the attendance of the ethics curricular units, with a statistically significant decrease in the total score for nursing students and a decrease not statistically significant for medical students. A multivariate analysis did not find any association between this decrease and gender, course, or age. The phenomenon of moral segmentation was observed, with better performance in the worker and judge dilemma, than in the doctor dilemma. These results highlight the need to reflect on the curricular strategies that can be implemented for health professionals to better develop moral competence and decision-making, allowing for the provision of humanized health care. (shrink)

The integration of standardized biomedical terminologies into a single, unified knowledge representation system has formed a key area of applied informatics research in recent years. The Unified Medical Language System (UMLS) is the most advanced and most prominent effort in this direction, bringing together within its Metathesaurus a large number of distinct source-terminologies. The UMLS Semantic Network, which is designed to support the integration of these source-terminologies, has proved to be a highly successful combination of formal coherence and broad scope. (...) We argue here, however, that its organization manifests certain structural problems, and we describe revisions which we believe are needed if the network is to be maximally successful in realizing its goals of supporting terminology integration. (shrink)

Gravity and Grace was the first ever publication by the remarkable thinker and activist, Simone Weil. In it Gustave Thibon, the priest to whom she had entrusted her notebooks before her untimely death, compiled in one remarkable volume a compendium of her writings that have become a source of spiritual guidance and wisdom for countless individuals.

I show that frequentism, as an explanation of probability in classical statistical mechanics, can be extended in a natural way to a decoherent quantum history space, the analogue of a classical phase space. The result is a form of finite frequentism, in which Gibbs’ concept of an infinite ensemble of gases is replaced by the quantum state expressed as a superposition of a finite number of decohering microstates. It is a form of finite and actual frequentism (as opposed to hypothetical (...) frequentism) insofar as all the microstates exist, in keeping with the decoherence-based Everett interpretation, and some versions of pilot-wave theory. (shrink)

Metaphysical anti-realism is a large and heterogeneous group of views that do not share a common thesis but only share a certain family resemblance. Views as different as mathematical nominalism—the view that numbers do not exist—, ontological relativism—the view that what exists depends on a perspective—, and modal conventionalism—-the view that modal facts are conventional—all are versions of metaphysical anti-realism. As the latter two examples suggest, relativist ideas play a starring role in many versions of metaphysical anti-realism. But what does (...) it mean for the existence of something to “depend on” a perspective, or for a modal fact to “depend on” a convention? We can distinguish between various dependence relations, giving rise to an array of drastically different forms of metaphysical anti-realism. This article offers a guided tour. I develop a systematic distinction between various forms of metaphysical anti-realism with a focus on the role of relativist ideas in this landscape. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Reviewed by:Desire of the Analysts: Psychoanalysis and Cultural CriticismVera J. Camden (bio)Desire of the Analysts: Psychoanalysis and Cultural Criticism. Ed. Greg Forter and Paul Allen Miller. New York: SUNY P, 2008. 258 pp.This collection takes up the uses of psychoanalysis for cultural studies in the new millennium. Its editors and contributors ask, “Where is psychoanalysis in contemporary thought?” At a time when the empirically based psychologies have long repudiated (...) the “talking cure” to the extent that the unconscious is not visible or easily measured, and when, on the other hand, psychoanalysis has been associated in the humanities with a radical political and social agenda, disappointed hopes for change have led many to throw the baby of psychoanalysis out with the bathwater of a utopian vision of transformation. The question now remains: “Whither psychoanalysis?” To answer this question (which is also a demand), the editors first acknowledge that the critique and curtailing of psychoanalytic thought in the cultural studies programs across the country in the last decade or so has been influenced by the works of Michel Foucault, his disciples, and the New Historicism. At the same time, they believe that the political, psychological, and moral dangers of embracing a knowing and cynical postmodernism that fosters hollow consumerism premised on modes of subjectivity that “neither ‘express’ interiority nor bear any relation to a lived past” are a real and present danger in contemporary life. “That the triumph of such a view has coincided with intellectuals’ renewed suspicion of psychoanalysis should, we believe, give us pause” (8). The essays that constitute the present volume thus insist on the persistence of the desire of the analyst: for knowledge of self and other, and by those who long for interpretive insight into interior lives and social places. The volume thus poses for its readers twin questions: “Why do we continue to desire psychoanalysis, and what should its role be in the cultural criticism of the new millennium?”This collection grew out of a conference organized around this question and thus reflects the varied but not necessarily interconnected papers offered in that setting. In an effort to provide some interconnections, the collection is divided into four sections grouped around the topics of psychoanalysis and the future of cultural criticism, collectivity, the author, and sexuality. The grouping does not, in my estimation, provide unity or coherence to the volume as a whole; nevertheless, each article emerges on its own terms as a strong contribution to the general field of psychoanalytic cultural criticism and critical theory. Henry Sussman’s “Psychoanalysis, Religion, and Cultural Criticism at the Millennium” provides an anchoring perspective to the volume, addressing with particular urgency the mutually transformative desire of and for analysis modeled on the transference/countertransference clinical encounter. This analogy [End Page 153] suggestively sets the stage for a like transformative intervention by the analyst in a cultural critique, while acknowledging that cultural studies provides the best interpretation and assessment of the ways that psychoanalysis operates historically and clinically in contemporary society. Sussman—and indeed many of the contributors—underscores the editors’ organizing declaration that since psychoanalysis derived from lived human experience it stands to reason that “analysis is both the product of and answer to suffering” (15).Thus it comes as something of a surprise that one of its editors, Greg Forter, in “F. Scott Fitzgerald, Psychobiography, and the Fin-de-Siecle Crisis in Masculinity,” locks the subject of psychoanalysis into a stranglehold with his presuppositions about the limits of history and the origins of psychoanalysis in the modern moment: “Because the theory and techniques of psychoanalysis were developed by analyzing modern men and women, psychoanalysis may be a theory of modern subjectivity rather than of subjectivity as such, and its mode of inquiry may be best suited to analyzing the phenomena of modernity” (148). Contrast this limiting and limited sense of the place of psychoanalysis in history (and the concomitant restriction of its utility expressed ironically in a volume with two major articles on premodern cultural texts!) to recent remarks in a new book by Christopher Bollas: “For thousands of years there has been an unconscious preconception of psychoanalysis. We [...] human beings [...] have been searching for... (shrink)

This paper deals with the recent policies introduced in Brazil in order to foster a public interest towards science. Persuasive messages and strategies aiming at increasing a public awareness of the importance of scientific literacy for the development of the country are introduced at different levels and targeting different kinds of publics. These policies are analysed in view of classical models of social influence and persuasion.

The central claim of this article is that post-truth requires a political and socio-economical perspective, rather than a moral or epistemological one. The article consists of two parts. The first part offers a critical examination of the dominant analyses of post-truth in terms of shifting standards of the origin and the evaluation of facts. Moreover, the claim that postmodernism is the cause of post-truth is examined and refuted. In the second part an alternative perspective is developed, centring around the notion (...) of gatekeepers. Rather than linking post-truth to bullshit and postmodernism, it should be understood as a symptom of a contemporary shift in the gatekeepers of truth and knowledge. Knowledge and truth are always mediated in society through the hands of gatekeeping institutions such as journalism or science. Post-truth is a symptom of a broader transformation of the gatekeeping institutions of our current society. It therefore requires a political philosophy of these institutional shifts and the new risks they involve. (shrink)

The present paper argues that, despite appearance to the contrary, Kierkegaard’s writings offer promising argumentational resources for addressing the problem of evil. According to Kierkegaard, however, in order to make use of these resources at all, one must necessarily be willing to shift the battleground, so to speak: from a third- to a genuine first-person perspective, namely the perspective of what Climacus dubs Religiousness A. All (yet also only) those who seek deliberate self-annihilation before God—a God in relation to whom (...) they perceive themselves always in the wrong—shall discover the ideal that an unwavering and in fact unconditional thankfulness (namely, for being forgiven) is to be considered the only appropriate attitude towards God and as such both necessary and sufficient for coming to terms with evil and suffering, at least in the life of someone making that discovery. I will argue that Kierkegaard’s (non-)pseudonymous writings provide reasons, at times unwittingly, for adopting the perspective of Religiousness A; however, I will also and ultimately argue that the principle of infinite thankfulness as a corollary of that perspective flounders when it comes to making sense of (the eschatological implications of) the suffering of others. (shrink)

Into wrestling with that question, Simone Weil put the very substance of her mind and temperament.

This book addresses a seemingly marginal and as yet sparsely discussed policy problem that turns out to open a window into longstanding debates at the very heart of normative ethics, metaethics, and practical rationality more broadly: Should we contact the last uncontacted peoples? Over the course of this book, I will explore grounds for three responses to this question: yes, no, and rejecting the question. First, I aim to show that even though the case of uncontacted people stirs up some (...) hard problems for theories of justice and well-being, they still warrant a presumption in favour of intervention: It seems that we would have similar duties towards uncontacted people as we are regularly taken to have towards contacted people similarly placed – if being contacted would be good for them. And it looks as though it would be, based on considerations of welfare more broadly and reasons of autonomy in particular. Still, intuitively there seems to be a strong presumption against intervention – or so widely accepted policies of non-intervention would suggest. I go on to explore two options for why intervention may be wrong overall: It may turn out to be harmful or impermissibly risky upon closer inspection of contingent circumstances; or it may be that extinguishing uncontacted cultures is bad independently of the interests of those living in them. Two further options challenge the viability of the question: I consider whether the case of uncontacted peoples undermines the very bases of our moral judgments, perhaps instantiating what Bernard Williams sought to capture with the idea of a relativism of distance. Lastly, I address whether the question of one’s self-interest in this matter challenges practical rationality more fundamentally by being a transformative choice or one between incomparable options. (shrink)

"What is required if men and women are to feel at home in society and are to recover their vitality? Into wrestling with that question, Simone Weil put the very substance of her mind and temperament. The apparently solid edifices of our prepossessions fall down before her onslaught like ninepins, and she is as fertile and forthright in her positive suggestions . . . she can be relied upon to toss aside the superficial and to come to grips with (...) the essential and the profound." -- Time Literary Supplement. (shrink)

We show that in the Maxwell–Lorentz theory of classical electrodynamics most initial values for fields and particles lead to an ill-defined dynamics, as they exhibit singularities or discontinuities along light-cones. This phenomenon suggests that the Maxwell equations and the Lorentz force law ought rather to be read as a system of delay differential equations, that is, differential equations that relate a function and its derivatives at different times. This mathematical reformulation, however, leads to physical and philosophical consequences for the ontological (...) status of the electromagnetic field. In particular, fields cannot be taken as independent degrees of freedom, which suggests that one should not add them to the ontology. (shrink)

Statements about the behavior of biochemical entities (e.g., about the interaction between two proteins) abound in the literature on molecular biology and are increasingly becoming the targets of information extraction and text mining techniques. We show that an accurate analysis of the semantics of such statements reveals a number of ambiguities that have to be taken into account in the practice of biomedical ontology engineering: Such statements can not only be understood as event reporting statements, but also as ascriptions of (...) dispositions or tendencies that may or may not refer to collectives of interacting molecules or even to collectives of interaction events. (shrink)