At first glance the three eukaryotic protein translocation machineries – the ER‐associated degradation (ERAD) transport apparatus of the endoplasmic reticulum, the peroxisomal importomer and SELMA, the pre‐protein translocator of complex plastids – appear quite different. However, mechanistic comparisons and phylogenetic analyses presented here suggest that all three translocation machineries share a common ancestral origin, which highlights the recycling of pre‐existing components as an effective evolutionary driving force.Editor's suggested further reading in BioEssays ERAD ubiquitin ligases Abstract.

Its author was a Carthusian monk. Offered here is a translation, with annotation and an important introduction, of the four books on natural philosophy, the predecessor of modern science.

The increased incidence of morbidity and mortality due to Clostridium difficile infection, had led to the emergence of fecal microbial transplantation (FMT) as a highly successful treatment. From this, a 32 strain stool substitute has been derived, and successfully tested in a pilot human study. These approaches could revolutionize not only medical care of infectious diseases, but potentially many other conditions linked to the human microbiome. But a second revolution may be needed in order for regulatory agencies, society and medical (...) practitioners to accept and utilize these interventions, monitor their long term effects, have a degree of control over their use, or at a minimum provide guidelines for donors and recipients. (shrink)

This 1997 book was the first English translation of all of Kant's writings on moral and political philosophy collected in a single volume. No other collection competes with the comprehensiveness of this one. As well as Kant's most famous moral and political writings, the Groundwork of the Metaphysics of Morals, the Critique of Practical Reason, the Metaphysics of Morals, and Toward Perpetual Peace, the volume includes shorter essays and reviews, some of which have never been translated before. The volume has (...) been furnished with a substantial editorial apparatus including translator's introductions and explanatory notes to each text by Mary Gregor, and a general introduction to Kant's moral and political philosophy by Allen Wood. There is also an English-German and German-English glossary of key terms. (shrink)

This 1997 book was the first English translation of all of Kant's writings on moral and political philosophy collected in a single volume. No other collection competes with the comprehensiveness of this one. As well as Kant's most famous moral and political writings, the Groundwork of the Metaphysics of Morals, the Critique of Practical Reason, the Metaphysics of Morals, and Toward Perpetual Peace, the volume includes shorter essays and reviews, some of which have never been translated before. The volume has (...) been furnished with a substantial editorial apparatus including translator's introductions and explanatory notes to each text by Mary Gregor, and a general introduction to Kant's moral and political philosophy by Allen Wood. There is also an English-German and German-English glossary of key terms. (shrink)

Chemokines (chemotactic cytokines) drive and direct leukocyte traffic. New evidence suggests that the unusual CCR6/CCL20 chemokine receptor/ligand axis provides key homing signals for recently identified cells of the adaptive immune system, recruiting both pro‐inflammatory and suppressive T cell subsets. Thus CCR6 and CCL20 have been recently implicated in various human pathologies, particularly in autoimmune disease. These studies have revealed that targeting CCR6/CCL20 can enhance or inhibit autoimmune disease depending on the cellular basis of pathogenesis and the cell subtype most affected (...) through different CCR6/CCL20 manipulations. Here, we discuss the significance of this chemokine receptor/ligand axis in immune and inflammatory functions, consider the potential for targeting CCR6/CCL20 in human autoimmunity and propose that the shared evolutionary origins of pro‐inflammatory and regulatory T cells may contribute to the reason why both immune activation and regulation might be controlled through the same chemokine pathway. (shrink)

Published in 1785, Immanuel Kant's Groundwork of the Metaphysics of Morals ranks alongside Plato's Republic and Aristotle's Nicomachean Ethics as one of the most profound and influential works in moral philosophy ever written. In Kant's own words, its aim is to identify and corroborate the supreme principle of morality, the categorical imperative. He argues that human beings are ends in themselves, never to be used by anyone merely as a means, and that universal and unconditional obligations must be understood as (...) an expression of the human capacity for autonomy and self-governance. As such, they are laws of freedom. This volume contains Mary Gregor's acclaimed translation of the text into English, revised by Jens Timmermann, and an accessible, updated introduction by Christine Korsgaard. (shrink)

Although evidence of teaching behaviour has been identified in some nonhuman species, human teaching appears to be unique in terms of both the breadth of contexts within which it is observed, and in its responsiveness to needs of the learner. Similarly, cultural evolution is observable in other species, but human cultural evolution appears strikingly distinct. This has led to speculation that the evolutionary origins of these capacities may be causally linked. Here we provide an overview of contrasting perspectives on the (...) relationship between teaching and cultural evolution in humans, and briefly review previous research which suggests that cumulative culture can occur without teaching. We then report the results of a novel experimental study in which we investigated how the benefits of teaching may depend on the complexity of the skill to be acquired. Participants were asked to tie knots of varying complexity. In our Teaching condition, opportunities to interact with an experienced partner aided transmission of the most complex knots, but not simpler equivalents, relative to exposure to completed products alone, and also relative to information about the process of completion. We conclude by considering the plausibility of various accounts of the evolutionary relationship between teaching and cultural evolution in humans. (shrink)

Aristotle's notion of experience plays an important role in his epistemology as the link between perception and memory on the one side, and higher cognitive capacities on the other side. However, Aristotle does not say much about it, and what he does say seems inconsistent. Notably, some passages suggest that it is a non-rational capacity, others that it is a rational capacity and that it provides the principles of science. This paper presents a unitary account of experience. It explains how (...) experience grows from perception and memory into a rational capacity, and in what way it provides the principles. (shrink)

The aim of this paper is to develop and defend an Attentional View of bodily awareness, on which attention is necessary for bodily awareness. The original formulation of the Attentional View is due to Marcel Kinsbourne. First, I will show that the Attentional View of bodily awareness as formulated by Kinsbourne is superior to other accounts in the literature for characterizing the relationship between attention and bodily awareness. Kinsbourne’s account is the only account in the literature so far which can (...) accommodate key neurological diseases such as personal neglect. Second, when I consider Kinsbourne’s view in more detail, I will argue that Kinsbourne’s Attentional View faces problems because it is too reductive. Kinsbourne deviates from the standard taxonomy on which there is a body schema and a body image. Instead he reduces the body image to the neural representation of the body in the somatosensory cortex, the body schema and attentional shifts. I will present two challenges to Kinsbourne’s view which demonstrate that Kinsbourne’s reduction of the body image is unsuccessful. Finally, I will present a revised version of the Attentional View that is both empirically adequate and philosophically satisfactory. (shrink)

This collection of essays by Gregor Sebba (1905-1985) reflects the curiosity and insight of his mind. The range of topics is wide, including philosophy and the history of ideas, literature and art; yet there is a single underlying theme - human creativity and the search for truth - pursued along paths as diverse as Greek tragedy, Eric Voegelin's concept of order in history, and the poetry of Rainer Maria Rilke and T.S.Eliot.

Gregor Moder’s Hegel and Spinoza: Substance and Negativity is a lively entry into current debates concerning Hegel, Spinoza, and their relation. Hegel and Spinoza are two of the most influential philosophers of the modern era, and the traditions of thought they inaugurated have been in continuous dialogue and conflict ever since Hegel first criticized Spinoza. Notably, eighteenth- and nineteenth-century German Idealists aimed to overcome the determinism of Spinoza’s system by securing a place for the freedom of the subject within (...) it, and twentieth-century French materialists such as Althusser and Deleuze rallied behind Spinoza as the ultimate champion of anti-Hegelian materialism. This conflict, or mutual rejection, lives on today in recent discussions about materialism. Contemporary thinkers either make a Hegelian case for the productiveness of concepts of the negative, nothingness, and death, or in a way that is inspired by Spinoza they abolish the concepts of the subject and negation and argue for pure affirmation and the vitalistic production of differences. Hegel and Spinoza traces the historical roots of these alternatives and shows how contemporary discussions between Heideggerians and Althusserians, Lacanians and Deleuzians are a variation of the disagreement between Hegel and Spinoza. Throughout, Moder persuasively demonstrates that the best way to read Hegel and Spinoza is not in opposition or contrast but together: as Hegel and Spinoza. (shrink)

The ideal of value free science states that the justification of scientific findings should not be based on non-epistemic (e.g. moral or political) values. It has been criticized on the grounds that scientists have to employ moral judgements in managing inductive risks. The paper seeks to defuse this methodological critique. Allegedly value-laden decisions can be systematically avoided, it argues, by making uncertainties explicit and articulating findings carefully. Such careful uncertainty articulation, understood as a methodological strategy, is exemplified by the current (...) practice of the Intergovernmental Panel on Climate Change (IPCC). (shrink)

This paper gives an explication of our intuitive notion of strength of justification in a controversial debate. It defines a thesis' degree of justification within the bipolar argumentation framework of the theory of dialectical structures as the ratio of coherently adoptable positions according to which that thesis is true over all coherently adoptable positions. Broadening this definition, the notion of conditional degree of justification, i.e.\ degree of partial entailment, is introduced. Thus defined degrees of justification correspond to our pre-theoretic intuitions (...) in the sense that supporting and defending a thesis t increases, whereas attacking it decreases, t's degree of justification. Moreover, it is shown that (conditional) degrees of justification are (conditional) probabilities. Eventually, the paper explains that it is rational to believe theses with a high degree of justification insofar as this strengthens the robustness of one's position. (shrink)

We give a construction of the square principle by means of forcing with finite conditions.

This essay examines what the philosophy of Paul Ricoeur can contribute to current debates on the role of spiritual exercise, or askēsis, in philosophical life. The influential work of Pierre Hadot and Michel Foucault has sparked a widespread interest in the ancient model of philosophy, variously described as a way of life, art of living, or care of the self. Ricoeur’s potential contribution to this conversation has been overlooked, largely because he does not discuss these themes explicitly or often. However, (...) Ricoeur’s early phenomenology of embodiment in The Voluntary and the Involuntary offers valuable insights regarding the exercises of self-transformation. After a brief survey of Ricoeur’s concept of askēsis, this essay draws on Ricoeur to demonstrate the merits of physical exercise, or gymnastic, in ethical and spiritual formation. Gymnastic, Ricoeur shows, can be a form of spiritual exercise. The final section of the paper then makes a similarly counterintuitive claim: namely, that reading is an embodied practice that can facilitate the ethical formation of the lived body. (shrink)

Based on a unique data set on US direct microloans, we study the funding determinants of interest-free peer-to-peer crowdlending aimed at borrowers in the US. By performing logistic regressions on funding success and Tobit regressions on the reversed funding time, the existence of a social underwriting by a third-party trustee and information in the description texts fostering the investors’ trust are shown to be the main predictors of successful funding. Regarding social impact, the possibility to empower women and groups of (...) borrowers appeals to the investors, whereas empowerment of the family or community beyond the borrowers themselves appears to remain unappreciated. When examining the vulnerability of the borrowers as a predictor, the results manifest differences amongst the attitudes of the investors towards social impact. In the subsample of non-endorsed loans, the investors appear to prefer to support borrowers with an immigration background. In contrast, this is not the case with endorsed loans. (shrink)

Mindfulness-based training programs are highly established in competitive and recreational sports. One of the best-known approaches is the Mindfulness-Acceptance-Commitment Approach by Gardner and Moore), which integrates mindfulness aspects of awareness, non-judgmental attitude, and focus. Based on these aspects, Thienot and colleagues developed and validated an English language sport-specific questionnaire, the so-called Mindfulness Inventory for Sport, for the assessment of mindfulness skills in athletes. The aim of this study is to psychometrically test a German language version of the MIS. To assess (...) the psychometric properties, the MIS-D was examined in an online survey with an integrated test–retest design for reliability, validity, and measurement invariance. The present results support the psychometric quality of the German language version of the MIS. Necessary replications should among others focus on checking the measurement invariance for further relevant subgroups. (shrink)

The paper deals with the question of the structure of knowledge and the precise relationship between propositional "knowledge that" and dispositional "knowledge how." In the first part of my essay, I provide an analysis of the term 'knowing how' and argue that the usual alternatives in the recent epistemological debate – knowing how is either a form of propositional or dispositional knowledge – are misleading. In fact it depends on the semantic and pragmatic context of the usage of this term (...) whether 'knowing how' refers to a type of dispositional knowledge, to propositional knowledge, or to a hybrid form of both. Only in the first case, can one say that dispositional know how cannot be reduced to any form of propositional knowledge. Yet, this case is the most interesting one to consider in the investigation of the nature of knowledge, if one assumes that knowing that p presupposes "having found out that p." Having found something out, however, presupposes certain acts of epistemic inquiry and corresponding epistemic abilities. Examined more carefully, it is shown that the dispositional knowledge-how is a necessary condition for propositional knowledge-that, hence propositional knowledge-that is a species of the dispositional knowledge-how. Accordingly, dispositional knowledge has to be understood as being at the very core of our notion of knowledge, including propositional knowledge. (shrink)

Cellular processes are highly dependent on a dynamic proteome that undergoes structural and functional rearrangements to allow swift conversion between different cellular states. By inducing proteasomal degradation of inhibitory or stimulating factors, ubiquitylation is particularly well suited to trigger such transitions. One prominent example is the remodelling of the centrosome upon cell cycle exit, which is required for the formation of primary cilia – antenna‐like structures on the surface of most cells that act as integrative hubs for various extracellular signals. (...) Over the last decade, many reports on ubiquitin‐related events involved in the regulation of ciliogenesis have emerged. Very often, these processes are considered to be initiated ad hoc, that is, directly before its effect on cilia biogenesis becomes evident. While such a temporal restriction may hold true for the majority of events, there is evidence that some of them are initiated earlier during the cell cycle. Here, we provide an overview of ubiquitin‐dependent processes in ciliogenesis and discuss available data that indicate such an early onset of proteolytic regulation within preceding cell cycle stages. (shrink)

Ordinary language and scientific discourse are filled with linguistic expressions for dispositional properties such as “soluble,” “elastic,” “reliable,” and “humorous.” We characterize objects in all domains – physical objects as well as human persons – with the help of dispositional expressions. Hence, the concept of a disposition has historically and systematically played a central role in different areas of philosophy ranging from metaphysics to ethics. The contributions of this volume analyze the ancient foundations of the discussion about disposition, examine the (...) problem of disposition within the context of the foundation of modern science, and analyze this dispute up to the 20th century. Furthermore, articles explore the contemporary theories of dispositions. (shrink)

Abstract. It is commonplace that economic globalization poses new challenges to legal theory. But instead of responding to these challenges, legal scholars often get caught up in heated yet purely abstract discussions of positivist and legal pluralist conceptions of the law. Meanwhile, economics-based theories such as "Law and Social Norms" have much less difficulty in analysing the newly arising forms of private and hybrid "governance without government" from a functional perspective. While legal theory has much to learn from these approaches, (...) we argue that they fail in one crucial point: They cannot uphold the analytical distinction between law and non-law. The reasons for this shortcoming are theory-immanent in that the economic theories' focus on efficiency and their actor-based perspective are necessarily blind to "law's own rationality." We therefore propose to further develop those functional approaches to the study of global governance by complementing them with elements from Niklas Luhmann's systems theory of law. This will provide us with a conceptual framework for analyzing the workings of global governance regimes without ignoring their potential for "legalisation" and "constitutionalisation." As we will show in three concrete examples (Corporate Social Responsibility, lex mercatoria , and internet regulation) we can thus describe the evolution of new forms of legal regulation beyond the nation-state. This will also allow us to draw some preliminary conclusions on the role of law in the context of globalization and, at the same time, show the direction for further empirical research. (shrink)

Climate models don’t give us probabilistic forecasts. To interpret their results, alternatively, as serious possibilities seems problematic inasmuch as climate models rely on contrary-to-fact assumptions: why should we consider their implications as possible if their assumptions are known to be false? The paper explores a way to address this possibilistic challenge. It introduces the concepts of a perfect and of an imperfect credible world, and discusses whether climate models can be interpreted as imperfect credible worlds. That would allow one to (...) use models for possibilistic prediction and salvage widespread scientific practice. (shrink)

Gregor Betz explores the following questions: Where are the limits of economics, in particular the limits of economic foreknowledge? Are macroeconomic forecasts credible predictions or mere prophecies and what would this imply for the way economic policy decisions are taken? Is rational economic decision making possible without forecasting at all?

The Metaphysics of Morals is Kant's major work in applied moral philosophy in which he deals with the basic principles of rights and of virtues. It comprises two parts: the 'Doctrine of Right', which deals with the rights which people have or can acquire, and the 'Doctrine of Virtue', which deals with the virtues they ought to acquire. Mary Gregor's translation, revised for publication in the Cambridge Texts in the History of Philosophy series, is the only complete translation of (...) the whole text, and includes extensive annotation on Kant's difficult and sometimes unfamiliar vocabulary. A new introduction by Roger Sullivan sets the work in its historical and philosophical context. This volume will be of wide interest to students of ethics and of legal and political philosophy. (shrink)

Menschliches Bewusstein findet sich immer schon als verkörpertes vor. Diese Einsicht steht im Zentrum des kognitionswissenschaftlichen Paradigmas der embodied cognition: Der Geist ist „innig an einen Körper gebunden und innig in seine Welt eingebettet“. Der Geist ist kein in einem vermeintlichen Innenraum verborgenes und von der Welt weitgehend gelöstes neuronales Netzwerk, sondern als eine dynamische Weise des leiblichen In-der-Welt-Seins zu verstehen. Mit der Philosophie der Verkörperung gewinnt die Theologie einen Gesprächspartner, der ihr hilft, ihre eigene Körpervergessenheit zu überwinden und Anschluss (...) an die biblischen Anthropologien zu gewinnen. Denn diese verstehen die menschliche Existenz grundsätzlich als leiblich verfasst. Aktuelle Forschungen an der Schnittstelle von Neurobiologie und Philosophie einerseits und Exegese und Systematik andererseits lassen sich so in einen spannenden Diskurs bringen, an dessen Ende eine neue interdisziplinäre Anthropologie stehen könnte. Der vorliegende Band eröffnet diesen Diskurs mit Beiträgen aus Philosophie, Exegese und Systematischer Theologie. (shrink)

"The objective of this book is to review the complex of issues in Soren Kierkegaard's concept of existence. It is evident that for Kierkegaard existence is always composed of three elements: namely, the subject, freedom, and the ethical. In the process of clarifying the relation between these three elements in the different stages of existence, the course of the development the individual must go through in order to become the single individual is described. "The study falls into four parts. The (...) first section describes the levels in existence on which as person attempts by his own powers to actualize the ethical ideals; in this stage the center of gravity for a person's effort still lies within the bounds of immanence. The second section describes a person's ethical and religious growth as it develops in relation to a transcendent power, whose highest expression is Christ as the revelation of God. The third section discusses the issues in existence that Kierkegaard himself designated as the most difficult of all for human thought. The last section points to the highest existential position to which philosophy in the broader sense and Christianity respectively can take a person. Kierkegaard utilizes these positions as a standard for evaluating existence within immanence and for Christian existence. (shrink)