Soluble components of Notch signalling can be applied to manipulate a central pathway essential for the development of metazoans and often deregulated in illnesses such as stroke, cancer or cardiovascular diseases. Commonly, the Notch cascade is inhibited by small compound inhibitors, which either block the proteolysis of Notch receptors by γ‐secretases or interfere with the transcriptional activity of the Notch intracellular domain. Specific antibodies can also be used to inhibit ligand‐induced activation of Notch receptors. Alternatively, naturally occurring endogenous inhibitors of (...) Notch signalling might offer a specific way to block receptor activation. Examples are the soluble variants of the canonical Notch ligand Jagged1 and the non‐canonical Notch ligand Dlk1, both deprived of their transmembrane regions upon ectodomain shedding, or the bona fide secreted molecule EGFL7. We present frequently used methods to decrease Notch signalling, and we discuss how soluble Notch inhibitors may be used to treat diseases. (shrink)

Approaches to foster motor creativity differ according to whether creative movements are assumed to be enacted creative ideas, or solutions to emerging motor problems that arise from task and environmental constraints. The twofold aim of the current study was to investigate whether an enriched physical education intervention delivered with a joint constraints-led and cognitive stimulation approach fosters motor creativity, and the responsiveness to the intervention is moderated by baseline motor and cognitive skills and sex; the intervention may benefit motor creativity (...) through gains in motor coordination, executive function, and creative thinking. Ninety-five children, aged 6–9 years, participated in a 6-month group randomized trial with specialist-led enriched PE vs. generalist-led conventional PE. Before and after the intervention, Bertsch’s Test of Motor Creativity, Movement Assessment Battery for Children, Random Number Generation task and Torrance Test of Creative Thinking were administered. Linear mixed models were run accounting for the random effects of data clusters. Multiple mediation analysis was performed to assess whether motor coordination, executive function and creative thinking mediated any improvement of motor creativity. Results showed that specialist-led enriched PE, compared to generalist-led conventional practice, elicited a more pronounced improvement in all motor creativity dimensions independently of baseline levels of motor and cognitive skills and sex; and improved motor creativity was partially mediated by improved motor coordination and, as regards motor flexibility, also by improved inhibitory ability. In conclusion, enriching PE with tailored manipulations of constraints and variability may enhance the ability to create multiple and original task-pertinent movements both directly and through indirect paths. The results are discussed extending to motor creativity a theoretical framework that distinguishes different creativity modes. The intervention may have fostered the generation of creative movements directly through the exposure to variation in constraints, activating the sensorimotor ‘flow’ mode of creativity that bypasses higher-order cognition, but also indirectly through a systematic and conscious convergence on solutions, activating the ‘deliberate’ mode of creativity that relies on inhibition to reject common or task-inappropriate movement categories. (shrink)

Several language experiments have been carried out on apes and other animals aiming to narrow down the presumed qualitative gap that separates humans from other animals. These experiments, however, have been driven by the understanding of language as a purely symbolic sign system, often connected to a profound disinterest for language use in real situations and a propensity to perceive grammatical and syntactic information as the only fundamental aspects of human language. For these reasons, the language taught to apes tends (...) to discard iconic and indexical elements in favour of symbolic signs. This paper sheds light on the iconic components of human language, with close attention to the iconic properties of language as present in the ape language experiments. We emphasise the role of the body in the interpretation and production of iconic signs, while demonstrating the need to take into account the Umwelt theory in the research paradigm of the experiments. Uexküll’s Umwelt theory is used to exemplify the methodological problems connected to the teaching of human language to other animal species; furthermore, we discuss how the modelling capacities of language affect the biological layer that constitutes the animal Umwelt. Language is analysed as a particular case of Umwelt transition, and as such its implications are further discussed in the article. With this paper, we enrich the discussion surrounding the human-ape pidgin language by advocating for the need to include iconic components as vital parts of this research area. With this inclusion, we uncover the inter-dependency of iconic, indexical and symbolic signs in human language, aiming to further develop the research paradigm of the ape language experiments. (shrink)

What should we believe when epistemic and practical reasons pull in opposite directions? The traditional view states that there is something that we ought epistemically to believe and something that we ought practically to (cause ourselves to) believe, period. More recent accounts challenge this view, either by arguing that there is something that we ought simpliciter to believe, all epistemic and practical reasons considered (the weighing view), or by denying the normativity of epistemic reasons altogether (epistemic anti-normativism). I argue against (...) both accounts and defend the traditional view. An agent can be blameworthy in doxastic dilemmas for complying with their practical but not their epistemic reasons. This reveals how epistemic reasons are normative: the concept of epistemic blame helps us track epistemic normativity. (shrink)

The quarantine model, recently proposed by Pereboom and Caruso, is one of the most influential models developed to date in the context of criminal justice. The quarantine model challenges the very idea of criminal punishment and asserts that nobody deserves punishment on a fundamental level. Instead, in order to deal with offenders, it proposes a series of incapacitation measures based on public safety concerns. In this article, we examine several objections to the quarantine model that demonstrate how, in our view, (...) it can be improved. These mainly pertain to (2.1) the difficulty of reliably identifying dangerous individuals and consequently the need to base confinement decisions on probability, and (2.2) the potential for the quarantine model not to properly deter certain crimes. Three additional objections are raised with respect to (3.1) the rights that are potentially suppressed in the quarantine model; (3.2) the role of “genetic justice”; and (3.3) the difficulty it faces accommodating reasons-responsiveness. Whereas these objections do not constitute knock-down arguments against the quarantine model, they highlight issues that invite closer scrutiny, at least if it is to be considered as a credible framework for the development of viable policies in criminal justice. (shrink)

Drawing upon the philosophical insights of Friedrich Schlegel, Walter Benjamin, Theodor W. Adorno, and Blixa Bargeld, this book explores the persistence of a critical-deconstructive approach to musical production, consumption, and reception in the German cultural sphere of the last two centuries.

Argues that there are moral grounds to use torture where the lives of the innocent are at stake.

The normative force of evidence can seem puzzling. It seems that having conclusive evidence for a proposition does not, by itself, make it true that one ought to believe the proposition. But spelling out the condition that evidence must meet in order to provide us with genuine normative reasons for belief seems to lead us into a dilemma: the condition either fails to explain the normative significance of epistemic reasons or it renders the content of epistemic norms practical. The first (...) aim of this paper is to spell out this challenge for the normativity of evidence. I argue that the challenge rests on a plausible assumption about the conceptual connection between normative reasons and blameworthiness. The second aim of the paper is to show how we can meet the challenge by spelling out a concept of epistemic blameworthiness. Drawing on recent accounts of doxastic responsibility and epistemic blame, I suggest that the normativity of evidence is revealed in our practice of suspending epistemic trust in response to impaired epistemic relationships. Recognizing suspension of trust as a form of epistemic blame allows us to make sense of a purely epistemic kind of normativity the existence of which has recently been called into doubt by certain versions of pragmatism and instrumentalism. (shrink)

The discourse on the fundamental issues raised by synthetic biology, such as biosafety and biosecurity, intellectual property, environmental consequences and ethical and societal implications, is still open and controversial. This, coupled with the potential and risks the field holds, makes it one of the hottest topics in technology assessment today. How a new technology is perceived by the public influences the manner in which its products and applications will be received. Therefore, it is important to learn how people perceive synthetic (...) biology. This work gathers, integrates and discusses the results of three studies of public perceptions of synthetic biology: an analysis of existing research on how media portray synthetic biology across 13 European countries and in the USA, the Meeting of Young Minds, a public debate between prospective politicians and synthetic biologists in the Netherlands and the experiences of citizen panels and focus groups in Austria, the UK and the USA. The results show that the media are generally positive in their reports on synthetic biology, rather unbalanced in their view of potential benefits and risks, and also heavily influenced by the sources of the stories, namely scientists and stakeholders. Among the prospective Dutch politicians, there were positive expectations as well as very negative ones. Some of these positions are also shared by participants in public dialogue experiments, such as not only the demand for information, transparency and regulation but also a sense of resignation and ineluctability of scientific and technological progress. (shrink)

Summary This short article goes back to the problem of the authenticity of the document found at Dem. 24.20–23, with wide implications for the reconstruction of Athenian nomothesia. Without providing a comprehensive response to M. H. Hansen’s recent KLIO article on the topic (M. H. Hansen, The Inserted Document at Dem. 24.20–23. Response to Mirko Canevaro, KLIO 101, 2019, 452–472; itself a response to a previous KLIO article by M. Canevaro), it clarifies some key issues and clears up some (...) important misunderstandings, also providing new evidence against the authenticity of the document. (shrink)

This paper offers a novel interpretation of Hans Jonas’ analysis of metabolism, the centrepiece of Jonas’ philosophy of organism, in relation to recent controversies regarding the phenomenological dimension of life-mind continuity as understood within ‘autopoietic’ enactivism (AE). Jonas’ philosophy of organism chiefly inspired AE’s development of what we might call ‘the phenomenological life-mind continuity thesis’ (PLMCT), the claim that certain phenomenological features of human experience are central to a proper scientific understanding of both life and mind, and as such central (...) features of all living organisms. After discussing the understanding of PLMCT within AE, and recent criticisms thereof, I develop a reading of Jonas’ analysis of metabolism, in light of previous commentators, which emphasizes its systematicity and transcendental flavour. The central thought is that, for Jonas, the attribution of certain phenomenological features is a necessary precondition for our understanding of the possibility of metabolism, rather than being derivable from metabolism itself. I argue that my interpretation strengthens Jonas’ contribution to AE’s justification for ascribing certain phenomenological features to life across the board. However, it also emphasises the need to complement Jonas’ analysis with an explanatory account of organic identity in order to vindicate these phenomenological ascriptions in a scientific context. (shrink)

It is often argued that there are no practical reasons for belief because we could not believe for such reasons. A recent reply by pragmatists is that we can often believe for practical reasons because we can often cause our beliefs for practical reasons. This paper reveals the limits of this recently popular strategy for defending pragmatism, and thereby reshapes the dialectical options for pragmatism. I argue that the strategy presupposes that reasons for being in non-intentional states are not reducible (...) to reasons to act. Pragmatists who want to preserve a motivational constraint on reasons therefore have exactly two options: either arguing that there are irreducible reasons for being in non-intentional states ; or arguing that we can believe directly for practical reasons. I argue that the prospects for the former option are dim because irreducible reasons to be in states are hard to square with the motivational constraint on reasons. Returning to the more traditional route of arguing for pragmatism by defending a version of doxastic voluntarism therefore seems to be the more promising way for pragmatists to go. (shrink)

In this volume Canevaro studies the 'state' documents preserved in the public speeches of the Demosthenic corpus. Offering a comprehensive account of the documents in the corpora of the orators and in the manuscript tradition, Canevaro summarizes previous scholarship and delineates a new methodology for analyzing the documents.

Antibiotic resistance (AR) is a major threat to public health and healthcare worldwide. In this article, we analyse and discuss the claim that taking actions to minimize AR is everyone's responsibility, focusing on individual moral responsibility. This should not be merely interpreted as a function of knowledge of AR and the proper use of antibiotics. Instead, we suggest a circumstantial account of individual responsibility for AR, where individuals do or do not engage in judicious antibiotic behaviour with different degrees of (...) voluntariness. Furthermore, we suggest a notion of responsibility as a virtue, in which individuals have the opportunity to develop a sensitivity towards the AR theme and, consequently, are capable of engaging, actively and voluntarily, in judicious antibiotic behaviour. The development of such sensitivity depends on the creation of adequate circumstances, that is individual capacities and availability of resources. (shrink)

In Arendt the domestic sphere is the other of the political sphere. In this contribution, however, the house will be described directly. Firstly, by reconstructing some of the different dichotomies included in the macro-differentiation between house and square; secondly by probing the connections and ties that bind house and square. Thirdly, by trying to read the modern emergence of the two poles «society» and «interiority» as a double process of simultaneous expansion and concentration of domestic semantics and domestic performances.

Accused persons who are subjected to a saturation level of negative media coverage may be denied an impartial hearing, which is perhaps the most important aspect of the right to a fair hearing. Despite this, the courts have generally held that the social imperative of prosecuting accused trumps the interests of the accused. The justification for an impartial hearing stems from the repugnance of convicting the innocent. Viewed dispassionately, this imperative is not absolute, given that every legal system condones procedures (...) which result in the conviction of some innocent people. While the importance of guarding against wrongful convictions has been overstated, the imperative to bring to trial all accused has been even more exaggerated. The legal system has displayed a capacity to deal with cases where the guilty walk free. The institutional integrity of the criminal justice system would be significantly compromised by convictions that are tarnished by pre-judgment. Confidence in the criminal justice system is more important than individual criminal accountability. The inability to receive an impartial hearing should result in a permanent stay. The only exception is where the alleged crime has the capacity to cause widespread fear or social unrest. This only applies in relation to serious acts of terrorism. This article focuses on recent legal fair trial developments in Australia, however, the analysis, reasoning and conclusion applies in relation to all jurisdictions where juries determine guilt and innocence. (shrink)

This is a collective study of philosophical questions to do with experts and expertise, such as: What is an expert? Who decides who the experts are? Should we always defer to experts? How should expertise inform public policy? What happens when the experts disagree? Must experts be unbiased? Does it matter what the source of the expertise is?

The method of reflective equilibrium (MRE) is a method of justification popularized by John Rawls and further developed by Norman Daniels, Michael DePaul, Folke Tersman, and Catherine Z. Elgin, among others. The basic idea is that epistemic agents have justified beliefs if they have succeeded in forming their beliefs into a harmonious system of beliefs which they reflectively judge to be the most plausible. Despite the common reference to MRE as a method, its mechanisms or rules are typically expressed in (...) a metaphorical or simplified manner and are therefore criticized as too vague. Recent efforts to counter this criticism have been directed towards the attempt to provide formal explications of MRE. This paper aims to supplement these efforts by providing an informal working definition of MRE. This approach challenges the view that MRE can adequately be characterized only in the negative as a set of anti-essentialisms. I argue that epistemic agents follow MRE iff they follow four interconnected rules, which are concerned with a minimalistic form of foundationalism, a minimalistic form of fallibilism, a moderate form of holism, and a minimalistic form of rationality. In the critical spirit of MRE, the corresponding working definition is, of course, provisional and revisable. In general, the aim is to contribute to a reflective equilibrium (RE) concerning MRE. If it is successful, this working definition provides a better grasp of the most basic elements of the method and thereby enhances our understanding of it. (shrink)

In many ways, questionable epidemiological measures by which the authorities restricted civic and private life during the COVID-19 pandemic have challenged many implied notions of the inviolability of citizens’ rights and freedoms, as well as obedience to state authority. It is a problem of the incommensurability between freedom and law seen through the conflict between personal rights and the demands of the common good. This article examines how a state of emergency, such as a pandemic, affects the perception of the (...) legitimacy of the State. In this, it relies on some key concepts from Carl Schmitt’s political theology, such as the “exception”, “the sociology of legal concepts”, the “nature of sovereignty”, the formal criterion of the political as a specific way of thinking, and acting and “stasiological” nature of the political. (shrink)

Many of our attitudes are non-culpable: there was nothing that we should have done to avoid holding them. I argue that we can still be blameworthy for non-culpable attitudes: they can impair our relationships in ways that make our full practice of apology and forgiveness intelligible. My argument poses a new challenge to indirect voluntarists, who attempt to reduce all responsibility for attitudes to responsibility for prior actions and omissions. Rationalists, who instead explain attitudinal responsibility by appeal to reasons-responsiveness, can (...) make sense of blameworthiness for non-culpable attitudes. In response, voluntarists could propose a revision of our actual practices. This would lead us into a quite different debate. (shrink)

The semeiotic of Charles Sanders Peirce is irreducibly triadic, positing that a sign mediates between the object that determines it and the interpretant that it determines. He eventually holds that each sign has two objects and three interpretants, standardizing quickly on immediate and dynamical for the objects but experimenting with a variety of names for the interpretants. The two most prominent terminologies are immediate/dynamical/final and emotional/energetic/logical, and scholars have long debated how they are related to each other. This paper seeks (...) to shed new light on the matter by reviewing the numerous manuscript drafts where Peirce develops the latter nomenclature while attempting to introduce his pragmatism to a general audience. It then goes on to examine an additional set of interpretants, intentional/effectual/communicational, and shows that the three different trichotomies can be understood as complementary, rather than redundant or conflicting. (shrink)

Das Buch beschreibt die Transformation des Diskurses der Kulturwissenschaft, der seit seinem Entstehen um die Jahrhundertwende auch die deutsch-jüdische Interkulturalität retten sollte, in einem Diskurs der politischen Theologie (Carl Schmitt und Gerschom Scholem), über den sich der katastrophale Trennungsprozess beider Kulturen vollstreckt.

We begin by introducing our readers to the Extended Mind Thesis and briefly discuss a series of arguments in its favour. We continue by showing of such a theory can be resisted and go on to demonstrate that a more conservative account of cognition can be developed. We acknowledge a stalemate between these two different accounts of cognition and notice a couple of issues that we argue have prevented further progress in the field. To overcome the stalemate, we propose to (...) focus on the ethical implications of these theories. We link work conducted on the Extended Mind Thesis with contemporary transhumanist research and claim that extended may be ethically preferred over embedded because it is a more progressive and inclusive theory. (shrink)

Several important questions in applied ethics – like whether to switch to a plant-based diet, reduce greenhouse gas emissions, or vote in elections – seem to share the following structure: if enough people ‘cooperate’ and become vegan for example, we bring about a better outcome; but what you do as an individual seems to make no difference whatsoever. Such collective action problems are often thought to pose a serious challenge to consequentialism. In response, I defend the Reactive Attitude Approach: rather (...) than focus only on the deontic status of (non-)cooperative acts – as existing consequentialist responses mostly do – consequentialists should also focus on when to praise or blame individuals. For example, even if your veganism does not change the overall outcome, consequentialists might still recommend praising you for your cooperative behavior. I make a consequentialist case for including praise and blame in our ethical practices around collective action and argue that doing so helps us capture important intuitions. I develop and defend these arguments by drawing on recent instrumentalist theories of blame and responsibility. (shrink)

ExcerptIn a letter to his friend and intellectual collaborator Theodor W. Adorno, on December 25, 1935, Walter Benjamin describes music as a field of inquiry “fairly remote” from his own.1 Several years later, in another letter to Max Horkheimer, he writes that the “state of musical affairs … could not be any more remote” for him.2 Yet despite these claims of unfamiliarity with aurality, there are numerous observations on acoustic phenomena throughout Benjamin's oeuvre. From his early essays on language to (...) his autobiographical studies and late works on critical historiography, Benjamin displays a keen sensitivity to sound that ranges from…. (shrink)

I present an explanatory argument for the reasons-first view: It is superior to knowledge-first views in particular in that it can both explain the specific epistemic role of perception and account for the shape and extent of epistemic justification.

This paper proposes substitutional definitions of logical truth and consequence in terms of relative interpretations that are extensionally equivalent to the model-theoretic definitions for any relational first-order language. Our philosophical motivation to consider substitutional definitions is based on the hope to simplify the meta-theory of logical consequence. We discuss to what extent our definitions can contribute to that.

Advances in artificial intelligence and robotics stand to change many aspects of our lives, including our values. If trends continue as expected, many industries will undergo automation in the near future, calling into question whether we can still value the sense of identity and security our occupations once provided us with. Likewise, the advent of social robots driven by AI, appears to be shifting the meaning of numerous, long-standing values associated with interpersonal relationships, like friendship. Furthermore, powerful actors’ and institutions’ (...) increasing reliance on AI to make decisions that may affect how people live their lives may have a significant impact on privacy while also raising issues about algorithmic transparency and human control. In this paper, building and expanding on previous works, we will look at how the deployment of Artificial Intelligence technology may lead to changes in identity, security, and other crucial values. We will discuss what challenges we may face in the process, while critically reflecting on whether such changes may be desirable. Finally, drawing on a series of considerations underlying virtue ethics, we will formulate a set of preliminary suggestions, which—we hope—can be used to more carefully guide the future roll out of AI technologies for human flourishing; that is, for social and moral good. (shrink)

I saggi di questo testo gravitano attorno a due fuochi: una diagnosi della soggettività contemporanea e il tentativo di sviluppare una critica all'altezza della sua vocazione emancipativa. Ciò che viene descritto è un processo di tendenziale emersione in superficie della relazione tra soggettività e politica; nessuna utopia col torcicollo, nessun nostalgismo, nessuna lamentela sulla superficialità della politica o paternale sulla superficialità dei soggetti. La scommessa, piuttosto, è quella di prendere le apparenze sul serio e quindi rinunciare a ogni forma di (...) ventriloquismo teorico, restituendo ai soggetti la parola senza per questo rinunciare alle ambizioni emancipative di una teoria sociale capace di fotografare, tracciare, scandagliare le trasformazioni della soggettività contemporanea e contemporaneamente le sue potenzialità e le sue contraddizioni. (shrink)

Due to the alarming rise of antibiotic resistance, medically unwarranted use of antibiotics has assumed new moral significance. In this paper, a thematic content analysis of focus group discussions was conducted to explore lay people’s views on the moral challenges posed by antibiotic resistance. The most important finding is that lay people are morally sensitive to the problems entailed by antibiotic resistance. Participants saw the decreasing availability of effective antibiotics as a problem of justice. This involves individual as well as (...) collective moral responsibility. Yet, holding agents responsible for their use of antibiotics involves varying degrees of demandingness. In our discussion, these findings are related to the contemporary ethical debate on antibiotic resistance and two proposals for the preservation of antibiotic effectiveness are compared to and evaluated against participants’ views. (shrink)

This volume provides a rigorous philosophical investigation of the rationales, challenges, and promises of the coming Space Age. Over the past decade, space exploration has made significant and accelerating progress, and its potential has attracted growing attention from science, states, businesses, innovators, as well as the media and society more generally. However, philosophical theorizing concerning the premises, values, meanings, and impacts of space exploration is still in its infancy, and this potentially immense field of study is far from mainstream yet. (...) This book advances outer space philosophy by integrating key scientific and societal debates sparked by recent developments in space research and activities with conceptual, existential, ethical, aesthetic, and political themes and concerns. It maps various regions of philosophical exploration, reflection, and speculation regarding humanity's present and future irradiation into outer space, to promote a broad, rich, and nuanced societal debate regarding this transformative enterprise, which is as stimulating as it can be disorienting. This book will be a fascinating philosophical and ethical exploration for academics, researchers and students interested in philosophy, space studies, science and technology studies, future studies, and sustainability. (shrink)