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)

This volume presents a number of controversial cases of enforced medical treatment from around the globe, providing for the first time a common, biopolitcal framework for all of them. Bringing together all these real cases guarantees that a new, more complete understanding of the topic will be within grasp for readers unacquainted with the aspects involved in these cases. On the one hand, readers interested mainly in the legal and medical dimensions of cases like those considered will benefit from the (...) explanation of the biopolitical framework within which each case develops. On the other hand, those focusing on only one of the situations presented here will find the parallels between the cases an interesting expansion of the complexity of the problem. Despite the book's ambitious goal, for those willing to use it as supplemental material or interested in only one of the cases, the chapters can function as self-standing pieces to be read separately. This volume will be a valuable tool for both academics and professionals. Bioethicists in both the analytic and continental traditions, will find the book interesting for not only the specific concepts and issues considered, but also for its constructive bridging of the two schools of thought. In addition to philosophers, the structure of this work will also appeal to lawyers, doctors, human rights activists, and anyone concerned in the most disparate way with real-life cases of enforced medical treatment. (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)

Demokratische Institutionen und rechtliche Regulierungsmechanismen wandeln sich grundlegend. Dieser Wandel ist Tendenzen der Metamorphose von Recht und Politik ausgesetzt: Tendenzen, von denen vorerst nur klar ist, dass sie erfolgen, nicht, in welchem Umfang und in welchen Formen. Um Klarheit uber diese Tendenzen gewinnen zu konnen, ist es erforderlich, erneut daruber nachzudenken, wie Politik, Verantwortung, Freiheit und Recht ins Verhaltnis zu setzen sind. Auf die dem Band vorangestellte Frage, ob es eine Freiheit ohne Recht gibt, finden sich in den Beitragen der (...) Autoren unterschiedliche Antworten.". (shrink)

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.

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)

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

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)

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)

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)

The immediate history of relations between man and nature is marked by mutual conflict. Until recently, nature had supremacy over man through the force of its natural power. During this period, the encounter with nature for man was a conflict with wholly implacable forces. Advances in science and technology have in some cases tamed the forces of nature, and now man can carry out planned and systematic violence against it. In so doing, he came to a privileged, but also sinful (...) relationship with nature. The end result proved devastating for both nature and for man. Man's quality of life has increased, but at an unacceptable cost for the environment, especially considering that both man and nature will be in dire straits in the not-so-distant future. It is urgent that man, as a reasonable officer of nature, finds ways to reconcile his relationship with nature. (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)

Das Buch stellt aktuelle Untersuchungsergebnisse aus Soziologie, Erziehungswissenschaft, Psychologie und anderen Disziplinen vor, die auf der Basis qualitativer Forschungsansätze oder aus einer Verbindung qualitativer und quantitativer Forschungsansätze entwickelt wurden.

OBJECTIVE: How outside factors affect physician decision making remains an open question of vital importance. We sought to investigate the importance of various influences on physician decision making when clinical guidelines differ from patient preference. -/- METHODS: An online survey asking 469 primary care providers (PCPs) across four practice sites whether they would order magnetic resonance imaging for a patient with uncomplicated back pain. Participants were randomized to one of four scenarios: a patient's preference for imaging (control), a patient's preference (...) plus a colleague's opinion against imaging (colleague), a patient's preference plus a professional society's recommendation against imaging (profession), or a patient's preference plus an accountable care organization's quality metric that measures physician use of imaging (ACO). Demographic information and the reasoning behind participants' decisions also were obtained. -/- RESULTS: A total of 168 PCPs completed the survey, yielding a 36% completion rate. A majority chose not to pursue imaging: control 68%, colleague 85%, profession 87%, and ACO 78%. Multivariate logistic regression revealed that participants were more likely not to order advanced imaging only when reminded of a professional society recommendation (P = 0.017). Regression also suggested that practice site exerted an effect on the primary outcome. Evidence-based medicine and clinical judgment were the most cited reasons for the decision. -/- CONCLUSIONS: Our results reinforce the potential to leverage professional societies to advance evidence-based medicine and reduce unnecessary testing. At the same time, practice site appeared to exert influence, suggesting that these recommendations must be part of local institutional culture to be effective. (shrink)

The principle of proportionality is seen as the highest peak of structural, logical thinking that enables balancing between constitutional principles and their interferences. So far, Alexy's weight formula has been the most advanced approach in structured balancing of proportionality stricto sensu, while this paper shows it as still too subjective. Despite judicial tests—or different, manifestly inappropriate reasonableness tests—proportionality stricto sensu hides some form of the jumping-to-conclusions bias, because the inference is made through a subjective lens. The paper presents structured legal (...) balancing (and hence reasoning) based on Bayes’ theorem. This paper, based on the connection between probability and hypothetical legal norms, transfers the four-part structure of proportionality into the relevant four-part structure of the Bayes tree. This transfer shows the first as flawed due to its failing to consider means that can have the same effects as the considered ones. Only by inclusion of the latter can the total probability of a considered case be established. Numerical proportionality à la Bayes can be further improved through the use of public-value weights that are obtained from surveys or online communities of people giving weights in the real time (collective wisdom). The Bayesian approach can also be used in adjudication as a control in assessing judicial standards in use. (shrink)

ZusammenfassungIn diesem Aufsatz wird eine kommunikations- und medientheoretische Untersuchung ausgewählter Divinationspraktiken unternommen. Im Zentrum stehen hierbei das Giftorakel der zentralafrikanischen Zande sowie die arabisch-islamische Geomantie. Dieses Unternehmen hat den Zweck, drei Thesen bezüglich Medien religiöser Kommunikation zu erproben, die sich dem Autor aus der Auseinandersetzung mit Ritualen und speziell Divinationsformen aus unterschiedlichen soziokulturellen Kontexten ergeben haben:1) Divinationsmedien unterscheiden sich in frappierender Weise von Medien der Alltagskommunikation; 2) diese besonderen Medien ermöglichen eine Kommunikation zwischen Wirklichkeitsbereichen und verkörpern damit ein fundamentales „Dazwischen“; (...) 3) von einer Innenperspektive betrachtet, werden Divinationsmedien oft als aktive Kommunikationspartner konzipiert und wahrgenommen – selbst wenn diese aus einer Beobachterperspektive unbelebte Paraphernalia sind.Um eine Grundlage für die Plausibilisierung dieser Thesen zu schaffen, ist anfänglich von Kommunikation und Medien sowie den Besonderheiten religiöser Kommunikation und Medien religiöser Kommunikation die Rede. Auf die detaillierte Beschreibung der Divinationspraktiken folgen ihre kommunikationstheoretische Analyse sowie eine zeichen- und medientheoretische Deutung dieser Ergebnisse.Das Ziel dieses Aufsatzes liegt neben der Plausibilisierung seiner Thesen auch darin, Impulse für die religionswissenschaftliche Debatte um Medien, Materialität und Performanz zu liefern. Gerade in den Ergebnissen der Divinationsforschung sieht David Morgan, wie er jüngst in Material religion schrieb, ein ertragreiches Feld. (shrink)

Block (Trends Cogn Sci 7:285–286, 2003) and Prinz (PSYCHE 12:1–19, 2006) have defended the idea that SSD perception remains in the substituting modality (auditory or tactile). Hurley and Noë (Biol Philos 18:131–168, 2003) instead argued that after substantial training with the device, the perceptual experience that the SSD user enjoys undergoes a change, switching from tactile/auditory to visual. This debate has unfolded in something like a stalemate where, I will argue, it has become difficult to determine whether the perception acquired (...) through the coupling with an SSD remains in the substituting or the substituted modality. Within this puzzling deadlock two new approaches have been recently suggested. Ward and Meijer (Conscious Cogn 19:492–500, 2010) describe SSD perception as visual-like but characterize it as a kind of artificially induced synaesthesia. Auvray et al. (Perception 36:416–430, 2007) and Auvray and Myin (Cogn Sci 33:1036–1058, 2009) suggest that SSDs let their users experience a new kind of perception. Deroy and Auvray (forthcoming) refine this position, and argue that this new kind of perception depends on pre-existing senses without entirely aligning with any of them. So, they have talked about perceptual experience in SSDs as going "beyond vision". In a similar vein, MacPherson (Oxford University Press, New York, 2011a) claims that “if the subjects (SSD users) have experiences with both vision-like and touch-like representational characteristics then perhaps they have a sense that ordinary humans do not” (MacPherson in Oxford University Press, New York, 2011a, p. 139). (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.

Many governments have seen digital health technologies as promising tools to tackle the current COVID-19 pandemic. A much-talked example in this context involves the recent deluge of digital contact tracing apps aimed at detecting Covid-19 exposure. In this short contribution we look at the bio-political justification of this phenomenon and reflect on whether DCT apps constitute, as it is often argued, a serious potential breach of our right to privacy. Despite praising efforts attempting to develop legal and ethical frameworks for (...) DCT apps’ usage; we argue that such endeavours are not sufficient to tackle the more fundamental problem of mass surveillance, which will remain largely unaddressed unless we deal with the biopolitical arguments presented and resort to a technical and structural defence. (shrink)

In Section 1, I introduce three views that explain human cognitive development from different standpoints: Marcus’s neo-nativism, standard neuroconstructivism, and neo-neuroconstructivism. In Section 2, I assess Marcus’s attempt to reconcile nativism with developmental flexibility. In Section 3, I argue that in structurally reconfiguring nativism, Marcus ends up transforming it into an unrecognizable form, and I claim that his view could be accommodated within the more general framework provided by standard neuroconstructivism. In Section 4, I focus on recent empirical findings in (...) neuropsychology and cultural/social neuroscience, and propose a friendly revision to standard neuroconstructivism, thus developing the neo-neuroconstructivist view. I conclude the article in Section 5 by analysing the implications of the results discussed in Section 4 for both neo-nativism and standard neuroconstructivism. 1 Introduction2 Marcus’s Neo-nativism3 Is Marcus’s Neo-nativism Really a Form of Nativism?4 Neo-neuroconstructivism and Dynamic Enskillment5 Conclusion. (shrink)

This paper addresses the biosemiotic dimensions of human relationship with captive animals and aims to uncover how these factors influence handling practices and human-animal interactions within zoological gardens. Zoological gardens are quintessential hybrid environments, and as such, they are places of interspecies interactions and mutual influences. These interactions are profoundly shaped by human attitudes towards animals. The roots of these attitudes can be found at the cultural and institutional levels as well as at the biosemiotic level. Previous studies have suggested (...) that keepers’ attitudes towards animals have direct influences on their handling style and, consequently, have an impact on animals’ perception of keepers and other humans. This suggests that the type of relationship between keepers and animals can translate into handling styles that may affect animals’ perceptions of humans and worsen or improve their welfare. In this paper, we present a case study involving chimpanzees’ keepers at the Tallinn Zoological Gardens. A series of interviews were conducted, which aimed to uncover the way keepers understand their relationships with captive animals and how this influences handling. This work offers a comparative approach by bringing forward the experiences of keepers who work with various animal species belonging to different taxa and class. Such an approach aims to highlight the biosemiotic factors behind the emergence of different types of keeper-animal relationships. We expect to uncover whether extremely different Umwelten may shape human-animal bonds. By highlighting the agency of animals in daily activities and work routine, we also aim to initiate a discussion on the way animals influence handling practices within zoological gardens. Our objective is to understand how individual animals influence handling practices within zoological gardens. (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)

BackgroundAlthough some of the most radical hypothesis related to the practical implementations of human enhancement have yet to become even close to reality, the use of cognitive enhancers is a very tangible phenomenon occurring with increasing popularity in university campuses as well as in other contexts. It is now well documented that the use of cognitive enhancers is not only increasingly common in Western countries, but also gradually accepted as a normal procedure by the media as well. In fact, its (...) implementation is not unusual in various professional contexts and it has its peak in colleges. Even when certain restrictions in the legislation of a country are indeed in place, they are without doubts easy to overcome. The legitimacy and appropriateness of such restrictions will not be the focus of our investigation.DiscussionOur concern is instead related to the moral and social reasons to publicly acknowledge the use of cognitive enhancers in competitive-selective contexts. These reasons are linked to a more neutral analysis of contemporary Western society: it is a fact that an increasing number of competitive-selective contexts have a substantial number of contenders using cognitive enhancers.SummaryThrough the use of five explicative examples, in this paper we want to analyse the problems related to its use. In particular, it will be our aim to show the tension between one of the main argument used by bio-liberals and the actual implementation of the drugs in competitive, or semi-competitive contexts. (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)

Is freedom a plausible political value for animals? If so, does this imply that animals are owed legal personhood rights or can animals be free but remain human property? Drawing on different conceptions of freedom, I will argue that while positive freedom, libertarian self-ownership, and republican freedom are not plausible political values for animals, liberal ‘option-freedom’ is. However, because such option-freedom is in principle compatible with different legal statuses, animal freedom does not conceptually imply a right to legal self-ownership. Nonetheless, (...) a concern for animal option-freedom means that humans do have a pro tanto duty of non-interference. Arguments familiar from the liberal tradition moreover imply that such a duty speaks for drastic reforms of existing animal law. But it does not imply wholesale abolitionism: it neither rules out positive duties towards animals nor means that we should abandon all interactions with animals. (shrink)

The aim of this paper is to better qualify the problem of online trust. The problem of online trust is that of evaluating whether online environments have the proper design to enable trust. This paper tries to better qualify this problem by showing that there is no unique answer, but only conditional considerations that depend on the conception of trust assumed and the features that are included in the environments themselves. In fact, the major issue concerning traditional debates surrounding online (...) trust is that those debates focus on specific definitions of trust and specific online environments. Ordinarily, a definition of trust is assumed and then environmental conditions necessary for trust are evaluated with respect to such specific definition. However, this _modus operandi_ fails to appreciate that trust is a rich concept, with a multitude of meanings and that there is still no strict consensus on which meaning shall be taken as the proper one. Moreover, the fact that online environments are constantly evolving and that new design features might be implemented in them is completely ignored. In this paper, the richness of the philosophical discussions about trust is brought into the analysis of online trust. I first provide a set of conditions that depend on the definition of trust that can be assumed and then discuss those conditions with respect to the design of online environments in order to determine whether they can enable (and under which circumstances) trust. (shrink)