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)

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)

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.

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)

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)

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)

Health care often involves ethically difficult situations that may disquiet the conscience. The purpose of this study was to develop a questionnaire for identifying various perceptions of conscience within a framework based on the literature and on explorative interviews about perceptions of conscience (Perceptions of Conscience Questionnaire). The questionnaire was tested on a sample of 444 registered nurses, enrolled nurses, nurses’ assistants and physicians. The data were analysed using principal component analysis to explore possible dimensions of perceptions of conscience. The (...) results showed six dimensions, found also in theory and empirical health care studies. Conscience was perceived as authority, a warning signal, demanding sensitivity, an asset, a burden and depending on culture. We conclude that the Perceptions of Conscience Questionnaire is valid for assessing some perceptions of conscience relevant to health care providers. (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)

Incest is a crime in most societies. In the United States, incest is punishable in almost every state with sentences going as far as 20 and 30 years in prison, and even a life sentence. Yet the reasons traditionally proffered in justification of criminalization of incest—respecting religion and universal tradition; avoiding genetic abnormalities; protecting the family unit; preventing sexual abuse and sexual imposition; and precluding immorality—at a close examination, reveal their under- and over-inclusiveness, inconsistency or outright inadequacy. It appears that (...) the true reason behind the long history of the incest laws is the feeling of repulsion and disgust this tabooed practice tends to evoke in the majority of population. However, in the absence of wrongdoing, neither a historic taboo nor the sense of repulsion and disgust legitimizes criminalization of an act. (shrink)

The pressures that led to the evolution of episodic memory have recently seen much discussion, but a fully satisfactory account of them is still lacking. We seek to make progress in this debate by taking a step backward, identifying four possible ways that episodic memory could evolve in relation to simulationist future planning—a similar and seemingly related ability. After distinguishing each of these possibilities, the paper critically discusses existing accounts of the evolution of episodic memory. It then presents a novel (...) argument in favor of the view that episodic memory is a by-product of the evolution of simulationist future planning. The paper ends by showing that this position allows for the maintenance of the traditional view that episodic memory operates on stored memory traces, as well as explaining a number of key features of episodic memory: its being subject to frequent and systematic errors, its neural co-location with the capacity for simulationist future planning, and the potential existence of non-human episodic memory. (shrink)

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)

Plants synthesize with photons, so we commonly say. This article on photosynthesis introduces a notion of concepts that are to be thought of as capital and yet natural. They constitute a metaphysics of meteora alloys and copiousness through “actively lacking” a “proper” notion of conception.

Many arguments have been made against gene editing. This paper addresses the commonly invoked argument that gene editing violates human dignity and is ultimately a subversion of human nature. There are several drawbacks to this argument. Above all, the concept of what human dignity means is unclear. It is not possible to condemn a practice that violates human dignity if we do not know exactly what is being violated. The argument’s entire reasoning is thus undermined. Analyses of the arguments involved (...) in this discussion have often led to the conclusion that gene editing contravenes the principle of genetic identity (genetic immutability) thereby subverting a requisite of human dignity and ultimately threatening human nature. This paper refutes these arguments and shows that any opposition to gene editing cannot rely on the human dignity argument. (shrink)

Während die bisherige Forschung überwiegend auf Rekonstruktion und Analyse des philosophischen und pädagogischen Werkes von Theodor Litt bezogen war, konzentrieren sich gegenwärtige Untersuchungen bedingt durch die Zunahme von ...

The defense of necessity, also known as the “choice of evils,” reflects popular moral intuitions and common sense: sometimes, breaking the rules is the right—indeed, the only—thing to do in order to avoid a greater evil. Citing a classic example, mountain climbers may break into a cabin to wait out a deadly snow storm and appropriate the owner’s provisions because their property violations are a lesser evil compared to the loss of life. At the same time, this defense contradicts the (...) fundamental principles of criminal responsibility in that it authorizes violation of rights of innocent bystanders. By allowing the mountain climbers to override the property rights of the cabin owner, the defense effectively forbids the cabin owner to use force in response—a different rule would perpetuate violence. This outcome is at odds with the basic criminal law doctrines. There is no general duty to rescue in Anglo-American law. Yet, by forbidding the cabin owner to use force, the defense of necessity essentially imposes on him the duty to forego his interests in favor of those of the mountain climbers. The paper explores the origins and boundaries of the defense of necessity. It argues that the existing public and private theories of necessity are unsatisfactory and concludes that a viable theory of necessity should be able to explain why it is sometimes permissible to override individual rights of citizens without their consent or fault. (shrink)

In this article, I try to go beyond the traditional objections to strict liability public welfare offenses and confront other possible justifications for punishing non-culpable conduct. Specifically, I consider the following arguments:Penalties for public welfare offenses are punishment by name only, thus traditional justifications for punishment are not needed;Even if those penalties are punishment, punishing those who produce or threaten significant harm to others is not necessarily unjust; andEven if such punishment is not entirely just, it is consistent with other (...) widely accepted criminal law doctrines. (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)

The book series Linguistische Arbeiten (LA) publishes high-quality work in linguistics that addresses current issues in synchrony and diachrony, theoretically or empirically oriented.

During much of the past century, it was widely believed that phonemes--the human speech sounds that constitute words--have no inherent semantic meaning, and that the relationship between a combination of phonemes (a word) and its referent is simply arbitrary. Although recent work has challenged this picture by revealing psychological associations between certain phonemes and particular semantic contents, the precise mechanisms underlying these associations have not been fully elucidated. Here we provide novel evidence that certain phonemes have an inherent, non-arbitrary emotional (...) quality. Moreover, we show that the perceived emotional valence of certain phoneme combinations depends on a specific acoustic feature--namely, the dynamic shift within the phonemes' first two frequency components. These data suggest a phoneme-relevant acoustic property influencing the communication of emotion in humans, and provide further evidence against previously held assumptions regarding the structure of human language. This finding has potential applications for a variety of social, educational, clinical, and marketing contexts. (shrink)

We propose that children employ specialized cognitive systems that allow them to recover an accurate “causal map” of the world: an abstract, coherent, learned representation of the causal relations among events. This kind of knowledge can be perspicuously understood in terms of the formalism of directed graphical causal models, or “Bayes nets”. Children’s causal learning and inference may involve computations similar to those for learning causal Bayes nets and for predicting with them. Experimental results suggest that 2- to 4-year-old children (...) construct new causal maps and that their learning is consistent with the Bayes net formalism. (shrink)

Humans are standouts in their propensity to trade. More specially, the kind of trading found in humans—featuring the exchange of many different goods and services with many different others, for the mutual benefit of all the involved parties—far exceeds anything that is found in any other creature. However, a number of important questions about this propensity remain open. First, it is not clear exactly what makes this propensity so different in the human case from that of other animals. Second, it (...) is not clear why other animals did not acquire this propensity to the extent that humans did. Third, it is not clear what explains the fact that the extent to which humans engage in trade is culturally highly variable. The paper argues that at the heart of the human-animal divergence in this propensity is the particular socio-cultural environment in which humans evolved. This has led them to sometimes, but not always, acquire the cognitive technology (writing, algebra, tallying devices, money, etc.) to support a sophisticated disposition and capacity for reciprocal cooperation, and deep and wide concepts of property and exchange value. (shrink)

Prilozhenie I. Chelovek v totalitarnom gosudarstve -- Prilozhenie II. Iz-pod glyb -- Prilozhenie III. Lenin i Bogdanov -- Prilozhenie IV. Voskresenie.