Membranous organelles allow sub‐compartmentalization of biological processes. However, additional subcellular structures create dynamic reaction spaces without the need for membranes. Such membrane‐less organelles (MLOs) are physiologically relevant and impact development, gene expression regulation, and cellular stress responses. The phenomenon resulting in the formation of MLOs is called liquid–liquid phase separation (LLPS), and is primarily governed by the interactions of multi‐domain proteins or proteins harboring intrinsically disordered regions as well as RNA‐binding domains. Although the presence of RNAs affects the formation and (...) dissolution of MLOs, it remains unclear how the properties of RNAs exactly contribute to these effects. Here, the authors review this emerging field, and explore how particular RNA properties can affect LLPS and the behavior of MLOs. It is suggested that post‐transcriptional RNA modification systems could be contributors for dynamically modulating the assembly and dissolution of MLOs. (shrink)

The existence of DNA methylation in insects has been a controversial subject over a long period of time. The recently completed genome sequence of the honeybee Apis mellifera has revealed the first insect with a full complement of DNA methyltransferases.1 A parallel study demonstrated that these enzymes are catalytically active and that Apis genes can be methylated in specific patterns.2 These findings establish bees as a model to analyze the function of DNA methylation systems in invertebrate organisms and might also (...) be important to understand evolutionary aspects of DNA methylation in higher eukaryotes. BioEssays 29: 208–211, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Many species maintain cytosine DNA methyltransferase (MTase) genes belonging to the Dnmt2 family. Prokaryotic modification‐restriction systems utilize DNA methylation to distinguish between self and foreign DNA, and cytosine methylation in eukaryotic DNA contributes to epigenetic mechanisms that control gene expression. However, Dnmt2 proteins display only low or no DNA MTase activity, making this protein family the odd and enigmatic family member. Recent evidence showed that Dnmt2 proteins are not DNA but RNA MTases with functions in biological processes as diverse as (...) stress responses and RNA‐mediated inheritance. These observations not only raise profound questions regarding the perceived substrate specificities of cytosine MTase, but also suggest links between DNA and RNA modification systems. Here, we speculate that Dnmt2 proteins might be part of an ancient cytosine modification toolbox that is used to successfully respond to environmental challenges, including constantly evolving RNA and DNA substrates. (shrink)

It was, until recently, accepted that the two classes of acetylcholine (ACh) receptors are distinct in an important sense: muscarinic ACh receptors signal via heterotrimeric GTP binding proteins (G proteins), whereas nicotinic ACh receptors (nAChRs) open to allow flux of Na+, Ca2+, and K+ ions into the cell after activation. Here we present evidence of direct coupling between G proteins and nAChRs in neurons. Based on proteomic, biophysical, and functional evidence, we hypothesize that binding to G proteins modulates the activity (...) and signaling of nAChRs in cells. It is important to note that while this hypothesis is new for the nAChR, it is consistent with known interactions between G proteins and structurally related ligand‐gated ion channels. Therefore, it underscores an evolutionarily conserved metabotropic mechanism of G protein signaling via nAChR channels.Also watch the Video Abstract. (shrink)

The prospect of consumable meat produced in a laboratory setting without the need to raise and slaughter animals is both realistic and exciting. Not only could such in vitro meat become popular due to potential cost savings, but it also avoids many of the ethical and environmental problems with traditional meat productions. However, as with any new technology, in vitro meat is likely to face some detractors. We examine in detail three potential objections: 1) in vitro meat is disrespectful, either (...) to nature or to animals; 2) it will reduce the number of happy animals in the world; and 3) it will open the door to cannibalism. While each objection has some attraction, we ultimately find that all can be overcome. The upshot is that in vitro meat production is generally permissible and, especially for ethical vegetarians, worth promoting. (shrink)

Alois Riehl was one of the few Kantian-inspired philosophers of the late nineteenth and early twentieth century who argued for a realist approach to Kant’s original doctrine. He therefore rejected prevailing idealist reconstructions and attempted to establish a view of Kant as an important forerunner of what he programmatically called ‘critical realism.’ In the present paper it will be shown what this exactly meant for the interpretation of Kant’s and especially Riehl’s own critique of idealism as a systematic position. In (...) particular, it is stated that anti-idealism in Riehlian terms amounts to a ‘realistic rehabilitation’ of Kantian things-in-themselves. Furthermore, some connections are drawn to early-twentieth century American realism. (shrink)

This article explores Franz Brentano's opposition to papal infallibility, and sets this in the context of his development as a Catholic scholar. An active participant in the Catholic revival of the nineteenth century, Brentano contributed to the emergence of neoscholasticism through his philosophical rehabilitation of Aristotle. Brentano ultimately left the Church however as the result of intensive scrutiny of his faith occasioned by his analysis of infallibility. This article explores this crisis of faith by analyzing, for the first time, Brentano's (...) position on papal infallibility, and suggesting ways that it informed his philosophical development. (shrink)

:In a recent paper in Cambridge Quarterly of Healthcare Ethics on the necessary conditions for morally responsible animal research David DeGrazia and Jeff Sebo claim that the key requirements for morally responsible animal research are an assertion of sufficient net benefit, a worthwhile-life condition, and a no-unnecessary-harm condition. With regards to the assertion of sufficient net benefit, the authors claim that morally responsible research offers unique benefits to humans that outweigh the costs and harms to humans and animals. In this (...) commentary we will raise epistemic, practical, and ethical challenges to DeGrazia and Sebo’s emphasis on benefits in the prospective assessment of research studies involving animals. We do not disagree with DeGrazia and Sebo that, at the theoretical level, the benefits of research justify our using animals. Our contribution intends to clarify, at the practical level, how we should understand benefits in the prospective assessment and moral justification of animal research. We argue that ASNB should be understood as an assessment of Expectation of Knowledge Production in the prospective assessment and justification of animal research. EKP breaks down into two further claims: that morally responsible research generates knowledge worth having and that morally responsible research is designed and executed to produce generalizable knowledge. We understand the condition called knowledge worth having as scientists’ testing a hypothesis that, whether verified or falsified, advances an important interest, and production of generalizable knowledge in terms of scientific integrity. Generalizable knowledge refers to experimental results that generalize to a larger population beyond the animals studied. Generalizable scientific knowledge is reliable, replicable, and accurately descriptive. In sum, morally responsible research will be designed and carefully executed to successfully test a hypothesis that, whether verified or falsified, advances important interests. Our formulation of EKP, crucially, does not require further showing that an experiment involving animals will produce societal benefits. (shrink)

In highly structured organisational fields individual efforts to deal rationally with uncertainty and constraints tend to lead, in the aggregate, to greater homogeneity in structure, culture and output. Drawing on institutional theory, this paper develops research propositions regarding the nature and scope of corporate social responsibility (CSR) engagement at trade/industry association level. The cases of the water and sewerage and film industries are used in order to test these propositions. The findings suggest that (a) trade associations in more homogeneous industries (...) are more likely to engage with CSR‐related issues; (b) trade associations in industries that face greater external scrutiny and threats to legitimacy are more likely to engage with CSR‐related issues; and (c) trade associations are more likely to engage with those substantive CSR issues that are of greater concern to the industry's most salient stakeholders. The findings also suggest that trade associations may have a greater tendency to engage in symbolic legitimation efforts through CSR if faced with the task of repairing industry legitimacy. (shrink)

We live in the Information Age. Advances over the past 50 years in computing technology have enabled ever-expanding capacity to generate, store, transfer, process and analyse information about people, societies, products, services, the environment—nearly every aspect of the world. In parallel, concerns over how such data is being used have emerged, focusing especially on issues of privacy and confidentiality. Yet as technological capabilities continue to expand, the debate over ethical uses of data inevitably has evolved as well. Whereas we used (...) to just talk about data, now there is great concern over Big Data. This chapter explores what, exactly, Big Data is; the ethical ramifications of its emergence, particularly for consent and anonymization; and what sorts of policy solutions are being proposed to address these emerging challenges. We will not defend one particular approach, but hope this chapter can be a useful reference for those who are contemplating difficult questions surrounding responsible management of Big Data. (shrink)

Ethical decision-making frameworks assist in identifying the issues at stake in a particular setting and thinking through, in a methodical manner, the ethical issues that require consideration as well as the values that need to be considered and promoted. Decisions made about the use, sharing, and re-use of big data are complex and laden with values. This paper sets out an Ethics Framework for Big Data in Health and Research developed by a working group convened by the Science, Health and (...) Policy-relevant Ethics in Singapore Initiative. It presents the aim and rationale for this framework supported by the underlying ethical concerns that relate to all health and research contexts. It also describes a set of substantive and procedural values that can be weighed up in addressing these concerns, and a step-by-step process for identifying, considering, and resolving the ethical issues arising from big data uses in health and research. This Framework is subsequently applied in the papers published in this Special Issue. These papers each address one of six domains where big data is currently employed: openness in big data and data repositories, precision medicine and big data, real-world data to generate evidence about healthcare interventions, AI-assisted decision-making in healthcare, public-private partnerships in healthcare and research, and cross-sectoral big data. (shrink)

This volume explores the relation between legal reasoning and logic from both a historical and a systematic perspective. The topics addressed include, among others, conditional legal acts, disjunctions in legal acts, presumptions and conjectures, conflicts of values, Jørgensen´s Dilemma, the Rhetor´s Dilemma, the theory of legal fictions and the categorization of contracts. The unifying problematic of these contributions concerns the conditional structures and, more particularly, the relationship between legal theory and legal reasoning in the context of conditions.

The future of health research will be characterised by three continuing trends: rising demand for health data; increasing impracticability of obtaining specific consent for secondary research; and decreasing capacity to effectively anonymise data. In this context, governments, clinicians and the research community must demonstrate that they can be responsible stewards of health data. IRBs and RECs sit at heart of this process because in many jurisdictions they have the capacity to grant consent waivers when research is judged to be of (...) particular value. However, several different terms are used to refer to this value, indicating a lack of conceptual clarity regarding the appropriate test for access to health data for research without consent. In this paper we do three things. First we describe the current confusion and instability in terminology relating to public interest in the context of consent waivers. Second we argue for harmonisation of terminology on the grounds of clarity, transparency and consistency. Third we argue that the term ‘public interest’ best reflects the normative work required to justify consent waivers because it is the broadest of the competing terms. ‘Public interest’ contains within its scope positive and negative implications of a study, as well as welfare, justice and rights considerations. In making this argument, we explain the normative basis for consent waivers, and provide a starting place for further discussion about the precise conditions in which a given study can be said to advance the public interest. Ipsos MORI study found that: … the public would be broadly happy with administrative data linking for research projects provided Those projects have social value, broadly defined. Data are de-identified. Data are kept secure. Businesses are not able to access the data for profit. (shrink)

Opponents to consciousness in fish argue that fish do not feel pain because they do not have a neocortex, which is a necessary condition for feeling pain. A common counter-argument appeals to the multiple realizability of pain: while a neocortex might be necessary for feeling pain in humans, pain might be realized differently in fish. This paper argues, first, that it is impossible to find a criterion allowing us to demarcate between plausible and implausible cases of multiple realization of pain (...) without running into a circular argument. Second, opponents to consciousness in fish cannot be provided with reasons to believe in the multiple realizability of pain. I conclude that the debate on the existence of pain in fish is impossible to settle by relying on the multiple realization argument. (shrink)

Studying consciousness requires contrasting conscious and unconscious perception. While many studies have reported unconscious perceptual effects, recent work has questioned whether such effects are genuinely unconscious, or whether they are due to weak conscious perception. Some philosophers and psychologists have reacted by denying that there is such a thing as unconscious perception, or by holding that unconscious perception has been previously overestimated. This article has two parts. In the first part, I argue that the most significant attack on unconscious perception (...) commits the criterion content fallacy: the fallacy of interpreting evidence that observers were conscious of something as evidence that they were conscious of the task-relevant features of the stimuli. In the second part, I contend that the criterion content fallacy is prevalent in consciousness research. For this reason, I hold that if unconscious perception exists, scientists studying consciousness could routinely underestimate it. I conclude with methodological recommendations for moving the debate forward. (shrink)

For people to contribute to discourse, they must do more than utter the right sentence at the right time. The basic requirement is that they add to their common ground in an orderly way. To do this, we argue, they try to establish for each utterance the mutual belief that the addressees have understood what the speaker meant well enough for current purposes. This is accomplished by the collective actions of the current contributor and his or her partners, and these (...) result in units of conversation called contributions. We present a model of contributions and show how it accounts for a variety of features of everyday conversations. (shrink)

Coronary by-pass surgery has been performed in hundreds of thousands of patients in the last 15 years with a high standard of technical and surgical perfection. The indications for this kind of surgery, however, are still controversial because in spite of many retrospective and several prospective studies it cannot be proven convincingly that in a given patient this surgical procedure will prolong life or prevent myocardial infarction. The present attempt to analyze the causes for this controversy shows that the main (...) reasons for this uncertainty lie: (a) in the enigma of the underlying (ischemic heart) disease itself, which is supposed to lend itself to surgical therapy; (b) in the inadequate methods available up until now for characterizing the state of the disease, its probable course, and its pathogenesis; and (c) in the professional group interests which have a momentum of their own. (shrink)

According to William Alston, we lack voluntary control over our propositional attitudes because we cannot believe intentionally, and we cannot believe intentionally because our will is not causally connected to belief formation. Against Alston, I argue that we can believe intentionally because our will is causally connected to belief formation. My defense of this claim is based on examples in which agents have reasons for and against believing p, deliberate on what attitude to take towards p, and subsequently acquire an (...) attitude A towards p because they have decided to take attitude A. From the possibility of intentional belief, two conclusions follow. First, the kind of control we have over our propositional attitudes is direct; it is possible for us to believe at will. Second, the question of whether what we believe is under our control ultimately depends on whether our will itself is under our control. It is, therefore, a question of the metaphysics of free will. (shrink)

Transdisciplinarity includes the assumption that within new institutional settings, scientific research becomes more closely responsive to practical problems and user needs and is therefore often subject to considerable application pressure. This raises the question whether transdisciplinarity affects the epistemic standards and the fruitfulness of research. Case studies show how user-orientation and epistemic innovativeness can be combined. While the modeling involved in all cases under consideration was local and focused primarily on features of immediate practical relevance, it was informed by theoretical (...) insights from basic research. Conversely, industrial research turns out sometimes to produce theoretical understanding. These findings highlight an interactive relationship between science and technology (moderate emergentism), which is distinct from the traditional view of a one-sided dependence of technology on science (cascade model) and from the newly received independence account (emergentism). (shrink)

As for most measurement procedures in the course of their development, measures of consciousness face the problem of coordination, i.e., the problem of knowing whether a measurement procedure actually measures what it is intended to measure. I focus on the case of the Perceptual Awareness Scale to illustrate how ignoring this problem leads to ambiguous interpretations of subjective reports in consciousness science. In turn, I show that empirical results based on this measurement procedure might be systematically misinterpreted.

In this paper, I argue that the rejection of doxastic voluntarism is not as straightforward as its opponents take it to be. I begin with a critical examination of William Alston's defense of involuntarism and then focus on the question of whether belief is intentional.

The COVID-19 pandemic has both exposed and created deep rifts in society. It has thrust us into deep ethical thinking to help justify the difficult decisions many will be called upon to make and to protect from decisions that lack ethical underpinnings. This paper aims to highlight ethical issues in six different areas of life highlighting the enormity of the task we are faced with globally. In the context of COVID-19, we consider health inequity, dilemmas in triage and allocation of (...) scarce resources, ethical issues associated with research, ethical considerations relating to tracing apps, and exit strategies such as immunity passports and COVID-19 vaccines. Finally, we consider environmental issues in light of COVID-19. The paper also offers some ethical reflection on these areas as many parts of the world contemplate the recovery phase. (shrink)

Consciousness scientists have not reached consensus on two of the most central questions in their field: first, on whether consciousness overflows reportability; second, on the physical basis of consciousness. I review the scientific literature of the 19th century to provide evidence that disagreement on these questions has been a feature of the scientific study of consciousness for a long time. Based on this historical review, I hypothesize that a unifying explanation of disagreement on these questions, up to this day, is (...) that scientific theories of consciousness are underdetermined by the evidence, namely, that they can be preserved “come what may” in front of (seemingly) disconfirming evidence. Consciousness scientists may have to find a way of solving the persistent underdetermination of theories of consciousness to make further progress. (shrink)

High degrees of uncertainty and a lack of effective therapeutic treatments have characterized the COVID-19 pandemic and the provision of drug products outside research settings has been controversial. International guidelines for providing patients with experimental interventions to treat infectious diseases outside of clinical trials exist but it is unclear if or how they should apply in settings where clinical trials and research are strongly regulated. We propose the Professional Oversight of Emergency-Use Interventions and Monitoring System as an alternative pathway based (...) on guidance developed for the ethical provision of experimental interventions to treat COVID-19 in Singapore. We support our proposal with justifications that establish moral duties for physicians to record outcomes data and for institutions to establish monitoring systems for reporting information on safety and effectiveness to the relevant authorities. Institutions also have a duty to support generation of evidence for what constitutes good clinical practice and so should ensure the unproven intervention is made the subject of research studies that can contribute to generalizable knowledge as soon as practical and that physicians remain committed to supporting learning health systems. We outline key differences between POEIMS and other pathways for the provision of experimental interventions in public health emergencies. (shrink)

Traditionally, the manufacturer/operator of a machine is held (morally and legally) responsible for the consequences of its operation. Autonomous, learning machines, based on neural networks, genetic algorithms and agent architectures, create a new situation, where the manufacturer/operator of the machine is in principle not capable of predicting the future machine behaviour any more, and thus cannot be held morally responsible or liable for it. The society must decide between not using this kind of machine any more (which is not a (...) realistic option), or facing a responsibility gap, which cannot be bridged by traditional concepts of responsibility ascription. (shrink)

"Rechtsphilosophie zwischen Ost und West" ist das erste Buch, das systematisch das frA1/4he Werk des bedeutenden chinesischen Rechtsgelehrten, Richters, Diplomaten und Schriftstellers John C.H. Wu (1899-1986) behandelt. Die Arbeit setzt sich in chronologischer Reihenfolge kritisch mit den VerAffentlichungen Wus im Zeitraum von 1921 bis 1936 auseinander. Wu, spAter Verfechter einer dynamischen Naturrechtslehre, versucht, die mehr pragmatisch-funktionale Rechtsauffassung der fA1/4hrenden amerikanischen Rechtsgelehrten mit dem von Kant geprAgten Denken R. Stammlers zu einer inneren Begegnung zu bringen. Gleichzeitig ist die Thematik chinesischen Rechtsdenkens (...) und Philosophierens immer gegenwArtig. Die Arbeit legt ein besonderes Augenmerk auf den EinfluA von Wus kulturellem Hintergrund auf die Auseinandersetzung mit westlichem Denken und umgekehrt auf den EinfluA seiner westlichen Ausbildung auf seine Analyse der chinesischen Gedankenwelt. Das Buch will verstArkt auf diesen wichtigen Denker aufmerksam machen und den Grundstein fA1/4r eine wissenschafliche Auseinandersetzung mit ihm legen. Der Leser bekommt nicht nur einen interessanten Einblick in die zeitgeschichtlichen, rechtsphilosophischen Auseinandersetzungen, er bekommt auf einem wenig begangenen Weg Zugang zur chinesischen Kultur. (shrink)

Theodor Adorno is a widely-studied figure, but most often with regard to his work on cultural theory, philosophy and aesthetics. The Sociology of Theodor Adorno provides the first thorough English-language account of Adorno's sociological thinking. Matthias Benzer reads Adorno's sociology through six major themes: the problem of conceptualising capitalist society; empirical research; theoretical analysis; social critique; the sociological text; and the question of the non-social. Benzer explains the methodological and theoretical ideas informing Adorno's reflections on sociology and illustrates Adorno's (...) approach to examining social life, including astrology, sexual taboos and racial prejudice. Benzer clarifies Adorno's sociology in relation to his work in other disciplines and the inspiration his sociology took from social thinkers such as Marx, Weber, Durkheim, Kracauer and Benjamin. The book raises critical questions about the viability of Adorno's sociological mode of procedure and its potential contributions and challenges to current debates in social science. (shrink)

In: M. Carrier, D. Howard & J. Kourany (eds), Science and the Social: Knowledge, Epistemic Demands, and Social Values, Pittsburgh: University of Pittsburgh Press (im Erscheinen).

The predominant view is that a study using health data is observational research and should require individual consent unless it can be shown that gaining consent is impractical. But recent arguments have been made that citizens have an ethical obligation to share their health information for research purposes. In our view, this obligation is sufficient ground to expand the circumstances where secondary use research with identifiable health information is permitted without explicit subject consent. As such, for some studies the Institutional (...) Review Board/Research Ethics Committee review process should not assess the practicality of gaining consent for data use. Instead the review process should focus on assessing the public good of the research, public engagement and transparency. (shrink)

This book offers a systematic and up-to-date account of the landscape of contemporary epistemology. It presupposes only a minimum of prior philosophical knowledge, and includes an account of the logical and conceptual tools needed for philosophical analysis. Focuses on the writings and ideas of W. Alston, R. Audi, L. BonJour, R. Chisholm, A. Goldman. H. Kornboith, K. Lehrer. A. Plantinga, W. V. Quine, E. Sosa, and B Stroud, among others; links particular theories and arguments to their chief proponents and critics.

Traditionally, the manufacturer/operator of a machine is held (morally and legally) responsible for the consequences of its operation. Autonomous, learning machines, based on neural networks, genetic algorithms and agent architectures, create a new situation, where the manufacturer/operator of the machine is in principle not capable of predicting the future machine behaviour any more, and thus cannot be held morally responsible or liable for it. The society must decide between not using this kind of machine any more (which is not a (...) realistic option), or facing a responsibility gap, which cannot be bridged by traditional concepts of responsibility ascription. (shrink)

It has been suggested that a rational being stands in what is called a “second-personal relation” to herself. According to philosophers like S. Darwall and Ch. Korsgaard, being a rational agent is to interact with oneself, to make demands on oneself. The thesis of the paper is that this view rests on a logical confusion. Transitive verbs like “asking”, “making a demand” or “obligating” can occur with the reflexive pronoun, but it is a mistake to assume that the reflexive and (...) the non-reflexive use exhibit the same logical grammar. The thesis that they do is in part motivated by the assumption that to show that my relation to you bears the same form as my practical self-relation is to show that, fundamentally, you are not an object for me to think about and act on, but a subject with whom to think and act together. I argue, to the contrary, that if my addressing you exhibited the same form as a relation I could literally be said to stand in to myself, then the nexus between us would be such that I am irretr.. (shrink)

Rational drug design is a method for developing new pharmaceuticals that typically involves the elucidation of fundamental physiological mechanisms. It thus combines the quest for a scientific understanding of natural phenomena with the design of useful technology and hence integrates epistemic and practical aims of research and development. Case studies of the rational design of the cardiovascular drugs propranolol, captopril and losartan provide insights into characteristics and conditions of this integration. Rational drug design became possible in the 1950s when theoretical (...) knowledge of drug-target interaction and experimental drug testing could interlock in cycles of mutual advancement. The integration does not, however, diminish the importance of basic research for pharmaceutical development. Rather, it can be shown that still in the 1990s, linear processes of innovation and the close combination of practical and epistemic work were interdependent. (shrink)

Eleven pairs of newly commissioned essays face off on opposite sides of fundamental problems in current theories of knowledge. Brings together fresh debates on eleven of the most controversial issues in epistemology. Questions addressed include: Is knowledge contextual? Can skepticism be refuted? Can beliefs be justified through coherence alone? Is justified belief responsible belief? Lively debate format sharply defines the issues, and paves the way for further discussion. Will serve as an accessible introduction to the major topics in contemporary epistemology, (...) whilst also capturing the imagination of professional philosophers. (shrink)

It is a widely shared view among philosophers of science that the theory-dependence (or theory-ladenness) of observations is worrying, because it can bias empirical tests in favour of the tested theories. These doubts are taken to be dispelled if an observation is influenced by a theory independent of the tested theory and thus circularity is avoided, while (partially) circular tests are taken to require special attention. Contrary to this consensus, it is argued that the epistemic value of theory-dependent tests has (...) nothing to do with the circularity or non-circularity of the test, but is instead based on the minimal empiricality and reliability of observations. Since theory-dependence does not in general prevent observations fulfilling these requirements, it should not be regarded as a phenomenon that is basically detrimental, but as neutral with respect to successful scientific knowledge gathering. (shrink)