In eukaryotic cells terminally misfolded proteins of the secretory pathway are retarded in the endoplasmic reticulum (ER) and subsequently degraded in a ubiquitin‐proteasome‐dependent manner. This highly conserved process termed ER‐associated protein degradation (ERAD) ensures homeostasis in the secretory pathway by disposing faulty polypeptides and preventing their deleterious accumulation and eventual aggregation in the cell. The focus of this paper is the functional description of membrane‐bound ubiquitin ligases, which are involved in all critical steps of ERAD. In the end we want (...) to speculate on how the modular architecture of these entities ensures the specificity of substrate selection and possibly accomplishes the transport of misfolded polypeptides from the ER into the cytoplasm. (shrink)

PurposeTo evaluate the prevalence and treatment patterns of speech and language disorders in Germany.MethodsA retrospective analysis of data collected from 32% of the German population, insured by the statutory German health insurance. We used The International Statistical Classification of Diseases and Related Health Problems, 10th revision, German Modification codes for stuttering, cluttering, and developmental disorders of speech and language to identify prevalent and newly diagnosed cases each year. Prescription and speech therapy reimbursement data were used to evaluate treatment patterns.ResultsIn 2017, (...) 27,977 patients of all ages were diagnosed with stuttering. Stuttering prevalence peaks at age 5 years. Cluttering was diagnosed in 1,800 patients of all ages. Developmental disorders of speech and language were identified in 555,774 AOK-insurants. Treatment data indicate a substantial proportion newly diagnosed stuttering individuals receive treatment, with slightly fewer than 20 sessions per year, on average. We confirmed a previous study showing increased rates of atopic disorders and neurological and psychiatric comorbidities in individuals with stuttering, cluttering, and developmental disorders of speech and language.ConclusionThis is the first nationwide study using health insurance data to analyze the prevalence and newly diagnosed cases of a speech and language disorder. Prevalence and gender ratio data were consistent with the international literature. The crude prevalence of developmental disorders of speech and language increased from 2015 to 2018, whereas the crude prevalence for stuttering remained stable. For cluttering, the numbers were too low to draw reliable conclusions. Proportional treatment allocation for stuttering peaked at 6 years of age, which is the school entrance year, and is later than the prevalence peak of stuttering. (shrink)

It has been shown that counterintuitive ideas from mythological and religious texts are more acceptable than other world knowledge violations. In the present experiment we explored whether this relates to the way they are interpreted. Participants were presented with verification questions that referred to either the literal or a metaphorical meaning of the sentence previously read, in a block-wise design. Both behavioral and electrophysiological results converged. At variance to the literal interpretation of the sentences, the induced metaphorical interpretation specifically facilitated (...) the integration of religious counterintuitions, whereas the semantic processing of non-religious counterintuitions was not affected by the interpretation mode. We suggest that religious ideas tend to operate like other instances of figurative language, such as metaphors, facilitating their acceptability despite their counterintuitive nature. (shrink)

Peer review is a widely accepted instrument for raising the quality of science. Peer review limits the enormous unstructured influx of information and the sheer amount of dubious data, which in its absence would plunge science into chaos. In particular, peer review offers the benefit of eliminating papers that suffer from poor craftsmanship or methodological shortcomings, especially in the experimental sciences. However, we believe that peer review is not always appropriate for the evaluation of controversial hypothetical science. We argue that (...) the process of peer review can be prone to bias towards ideas that affirm the prior convictions of reviewers and against innovation and radical new ideas. Innovative hypotheses are thus highly vulnerable to being “filtered out” or made to accord with conventional wisdom by the peer review process. Consequently, having introduced peer review, the Elsevier journal Medical Hypotheses may be unable to continue its tradition as a radical journal allowing discussion of improbable or unconventional ideas. Hence we conclude by asking the publisher to consider re-introducing the system of editorial review to Medical Hypotheses. (shrink)

PurposeChildhood onset speech fluency disorder is possibly related to dopaminergic dysfunction. Mesencephalic hyperechogenicity detected by transcranial ultrasound might be seen as an indirect marker of dopaminergic dysfunction. We here determined whether adults who stutter since childhood show ME.MethodsWe performed TCS in ten AWS and ten matched adults who never stuttered. We also assessed motor performance in finger tapping and in the 25 Foot Walking test.ResultsCompared to controls, AWS showed enlarged ME on either side. Finger tapping was slower in AWS. Walking (...) cadence, i.e., the ratio of number of steps by time, tended to be higher in AWS than in control participants.DiscussionThe results demonstrate a motor deficit in AWS linked to dopaminergic dysfunction and extending beyond speech. Since iron deposits evolve in childhood and shrink thereafter, ME might serve as an easily quantifiable biomarker helping to predict the risk of persistency in children who stutter. (shrink)

Friedrich Nietzsche, den Gottfried Benn als das "grosste Ausstrahlungsphanomen der Geistesgeschichte" bezeichnete, steht im Zentrum dieses Buches. Es enthalt die Vortrage der Ringvorlesung, welche die Freiburger Forschungsstelle "Nietzsche-Kommentar" zum 100. Geburtstag der Heidelberger Akademie der Wissenschaften organisierte. - In der konstruktiven Auseinandersetzung mit Nietzsche beleuchten die Aufsatze Nietzsches Bedeutung als Leitfigur moderner Lebensphilosophie, Kulturdiagnose und Anthropologie. Nietzsches Kritik an der philosophischen Tradition, sein Konzept der Umwertung, seine Psychologie, sein Geschichtsdenken, seine Beziehung zu Darwin, Schopenhauer, Wagner und Heidegger, seine Lyrik sowie (...) die Charakteristika seines Stils gehoren zum breitgefacherten Themenspektrum.Der Band enthalt Beitrage von Dieter Borchmeyer, Gunter Figal, Hans-Martin Gauger, Volker Gerhardt, Katharina Gratz, Lore Huhn, Helmuth Kiesel, Ludger Lutkehaus, Klaus Monig, Barbara Neymeyr, Annemarie Pieper, Jochen Schmidt und Andreas Urs Sommer. (shrink)

Metaphysics is, as Adorno once notes, the nuisance of philosophy. On the one hand, metaphysics is the reasons of philosophy's existence; on the other hand, it is nearly impossible to characterise metaphysics precisely. This tension is reflected with reference to the contemporary political and cultural situation in Adorno's "Meditations on Metaphysics", the last part of his opus magnum *Negative Dialectics*. The essays in this volume are devoted to different facets of Adorno's examination of metaphysics. They do, however, not only concern (...) themselves with Adorno's metaphysical reflections in a narrow sense, but also extend to other themes Adorno relates to metaphysics: critique of concepts, history, truth, and materialism. Thereby, they render a hardly investigated topic of the *Negative Dialectics* accessible. -/- Contributors: Emil Angehrn, Dirk Braunstein, Peggy H. Breitenstein, Gunnar Hindrichs, Axel Hutter, Philip Hogh, Christian Iber, Julia Jopp, Guido Kreis, Ansgar Martins, Brian O'Connor, Mario Schärli, Marc Nicolas Sommer, Tilo Wesche. (shrink)

Heidegger hielt die unter dem Titel Geschichte des Zeitbegriffs angekundigte Vorlesung im Sommer-Semester 1925 in der Marburger Universitat. Er gelangte jedoch nicht mehr zur Ausfuhrung der zentralen Thematik. Der Themenkreis der Vorlesung ist mit der Nennung des Untertitels abgesteckt: Prolegomena zu einer Phanomenologie von Geschichte und Natur. Heideggers thematische Uberlegungen beginnen mit einer Kennzeichnung der Situation von Philosophie und Wissenschaft in der zweiten Halfte des 19. Jahrhunderts und stellen das seiner Deutung nach entscheidende Ereignis dieser Zeit heraus: den Durchbruch (...) der Phanomenologie als philosophische Forschung. Er untersucht ihre wesentlichen Entdeckungen, verteidigt sie gegen Missverstandnisse, um dann seinerseits Kritik vorzubringen, wo die Phanomenologie ihrer Forderung zu den Sachen selbst nicht gerecht wird. (shrink)

Nietzsche hat die Hauptgedanken seines Philosophierens in den von ihm publizierten oder zur Publikation vorbereiteten Werken zur Sprache gebracht. Sein umfangreicher Nachlass ist hilfreich, um die Genese dieser Werke zu verstehen, kann - z. B. gegen Martin Heidegger - jedoch nicht als das Eigentliche und Wesentliche von Nietzsches Philosophie betrachtet werden. Umso dringlicher ist es, zu einer genauen und sorgfältigen Lektüre von Nietzsches Werken zurückzukehren. Dies wird versucht im Nietzsche-Kommentar der Heidelberger Akademie der Wissenschaften, der in den nächsten Jahren (...) entstehen wird. Der vorliegende Aufsatz stellt Probleme der Kommentierungsarbeit anhand von Nietzsches Spätschrift Götzen-Dämmerung zur Diskussion. (shrink)

Im Mittelpunkt des Bandes steht mit Nietzsches Nachlass derjenige Teil seines Schaffens, von dem seit jeher eine besondere Faszination ausging. Sein Status ist bis heute höchst umstritten. Handelt es sich bei den nachgelassenen Aufzeichnungen um Skizzen und Vorstufen, um Bausteine für neue Werke oder gar – wie etwa Martin Heidegger meinte – um das ‚eigentliche‘ Werk Nietzsches? Außer Frage steht, dass der Nachlass besondere editorische und interpretatorische Schwierigkeiten aufwirft. Zugleich herrscht aber weitgehender Konsens darüber, dass er für das Verständnis (...) von Nietzsches Denken und Schreiben unverzichtbar ist, denn viele seiner zentralen Gedanken sind im Nachlass anders, mitunter scheinbar deutlicher, bisweilen überhaupt nur hier formuliert. Die Beiträge gehen diesen Spannungsverhältnissen nach, indem sie sowohl am Beispiel konkreter Einzelfälle als auch grundsätzlich den angemessenen Umgang mit Nietzsches nachgelassenen Schriften diskutieren. (shrink)

Given some links between Lyndon’s Interpolation Theorem, term distribution, and Sommers and Englebretsen’s logic, in this contribution we attempt to capture a sense of interpolation for Sommers and Englebretsen’s Term Functor Logic. In order to reach this goal we first expound the basics of Term Functor Logic, together with a sense of term distribution, and then we offer a proof of our main contribution.

En esta contribución proponemos una representación de un fragmento de la silogística estadística de Thompson usando la lógica de términos de Sommers. El resultado es una interpretación terminista de la silogística estadística.

Der erste Teilband des umfangreichen Seminarbandes 84 der Gesamtausgabe gehort in den grossen Kontext von Martin Heideggers Auseinandersetzung mit Immanuel Kant und Gottfried Wilhelm Leibniz. Leibniz ist fur Heidegger von herausragender Bedeutung fur die Geschichte der neuzeitlichen Metaphysik zwischen Descartes und Kant. Im Band 84.1 kommen drei Seminare zu Kant und ein Seminar zu Leibniz erstmals zur Veroffentlichung. Die drei Kant-Seminare befassen sich mit Kants Preisschrift uber die aFortschritte der Metaphysik (Sommer 1931), mit Kants aTranszendentaler Dialektik aus der (...) Kritik der reinen Vernunft im Hinblick und Vorgriff auf Kants praktische Philosophie (Winter 1931/32) und nochmals mit aHauptstucken aus der Kritik der reinen Vernunft (Sommer 1934). Das Leibniz-Seminar (Winter 1935/36) gibt erstmals eine grundlegende und wegweisende Gesamtinterpretation der aMonadologie. (shrink)

In this paper we propose a tableaux method for the intermediate syllogistic of Peterson and Thompson by using the algebra of Sommers and Englebretsen. The result is an analytic tableaux method capable of modeling inference in basic, relational, and intermediate syllogistic.

Online supplement, "Mulsow: Additions to Notes drawn from the 2002 edition of Moderne aus dem Untergrund" full versions of nearly 300 notes that were truncated in the print edition. Hosted on H. C. Erik Midelfort's website. Martin Mulsow's seismic reinterpretation of the origins of the Enlightenment in Germany won awards and renown in its original German edition, and now H. C. Erik Midelfort's translation makes this sensational book available to English-speaking readers. In Enlightenment Underground, Mulsow shows that even in (...) the late seventeenth century some thinkers in Germany ventured to express extremely dangerous ideas, but did so as part of a secret underground. Scouring manuscript collections across northern Europe, Mulsow studied the writings of countless hitherto unknown radical jurists, theologians, historians, and dissident students who pushed for the secularization of legal, political, social, and religious knowledge. Often their works circulated in manuscript, anonymously, or as clandestinely published books. Working as a philosophical microhistorian, Mulsow has discovered the identities of several covert radicals and linked them to circles of young German scholars, many of whom were connected with the vibrant radical cultures of the Netherlands, England, and Denmark. The author reveals how radical ideas and contributions to intellectual doubt came from Socinians and Jews, church historians and biblical scholars, political theorists, and unemployed university students. He shows that misreadings of humorous or ironic works sometimes gave rise to unintended skeptical thoughts or corrosively political interpretations of Christianity. This landmark book overturns stereotypical views of the early Enlightenment in Germany as cautious, conservative, and moderate, and replaces them with a new portrait that reveals a movement far more radical, unintended, and puzzling than previously suspected. (shrink)

The aim of this paper is to examine the philosophical sources of some of the criticisms made in the second half of the 20th century to the practices and the main assumptions of historiography. In particular, the influence of the writings by Nietzsche dedicated to European Historicism on the renewed concept of history which is imposed in the twentieth century from the thought of Heidegger and Foucault. The divergent concepts of historical time and existential temporality, as well as those of (...) narrative unity and continuity of historical events, are the concepts that mainly fall under the critical scrutiny of these thinkers. Archaeological investigations that Foucault devotes to institutions and procedures of the European past are mentioned as examples of the critical review of traditional historiography. (shrink)

abstract G. A. Cohen argues that egalitarians should compensate for expensive tastes or for the fact that they are expensive. Ronald Dworkin, by contrast, regards most expensive tastes as unworthy of compensation — only if a person disidentifies with his own such tastes (i.e. wishes he did not have them) is compensation appropriate. Dworkinians appeal, inter alia, to the so‐called ‘first‐person’ or ‘continuity’ test. According to the continuity test, an appropriate standard of interpersonal comparison reflects people's own assessment of their (...) relative standing: Person A can only legitimately demand compensation from person B if he regards himself as worse off, all things considered, than B. The typical bearer of expensive tastes does not regard herself as being worse off than others with less expensive tastes. Hence, in the typical case, pace Cohen, compensation for expensive tastes is inappropriate. The article scrutinizes this rationale for not compensating for expensive tastes. Especially, we try to bolster the continuity test by relating it to Dworkin's distinction between integrated and detached values, pointing out that an argument for the continuity test can be built on the assumption that equality has integrated value. In brief, the point is that a metric of equality should be assessed, partly, in virtue of its consequences for related ideals. One of these is the kind of justificatory community promoted by the continuity test. We defend this view against an objection to the effect that equality is a detached value. We conclude that the continuity test constitutes a strong foothold for the resourcist egalitarian reluctance to compensate people for their expensive tastes. (shrink)

Consent governs innumerable everyday social interactions, including sex, medical exams, the use of property, and economic transactions. Yet little is known about how ordinary people reason about the validity of consent. Across the domains of sex, medicine, and police entry, Study 1 showed that when agents lack autonomous decision-making capacities, participants are less likely to view their consent as valid; however, failing to exercise this capacity and deciding in a nonautonomous way did not reduce consent judgments. Study 2 found that (...) specific and concrete incapacities reduced judgments of valid consent, but failing to exercise these specific capacities did not, even when the consenter makes an irrational and inauthentic decision. Finally, Study 3 showed that the effect of autonomy on judgments of valid consent carries important downstream consequences for moral reasoning about the rights and obligations of third parties, even when the consented-to action is morally wrong. Overall, these findings suggest that laypeople embrace a normative, domain-general concept of valid consent that depends consistently on the possession of autonomous capacities, but not on the exercise of these capacities. Autonomous decisions and autonomous capacities thus play divergent roles in moral reasoning about consent interactions: while the former appears relevant for assessing the wrongfulness of consented-to acts, the latter plays a role in whether consent is regarded as authoritative and therefore as transforming moral rights. (shrink)

In the second half of the nineteenth century, France was the main site of the controversy around the so-called eoliths, supposedly human-made tools of Tertiary Europe. In contrast to the more common situation where scientists have to make sure that an object stabilized in a laboratory is not an artifact of the lab but a natural object, in the eoliths debates the opposite was the case. The eolith proponents tried to render plausible the object's artificial, that is human, origin. In (...) their case, the objects would only be of scientific interest if they were artifacts not geofacts (naturally flaked stones). The paper ties in with existing literature on the French eoliths movement and investigates the successive eoliths debates in Britain. In Bruno Latour's terms, eoliths as archaeological evidence for Tertiary Man in Europe could gain in reality through a successful enlisting of the collaboration of human and non-human actors such as scientists, theories, publications, taxonomies, technologies, institutions, etc. Indeed, networks were established among scientists, preferably of powerful institutions, the 'tools' were integrated or denied a place in existing taxonomies of prehistoric artifacts, experiments were carried out to demonstrate their chance or designed origin, and their convergence or incompatibility with a certain theoretical framework was discussed. Arguments often revolved around questions of negative evidence, since both proponents and opponents of eoliths as tools were aware of the fact that the eoliths' strongest tie to reality would be evidence of the toolmakers themselves. Several known hominid fossils, among them those of doubtful age, were thus proposed as Tertiary shapers of the 'tools'. These hypothetical 'Englishmen' and their supposed artifacts were enmeshed in particular theories of human evolution, marked as they were by the racism and nationalism widespread at the time. (shrink)

Divided into four parts, this treatise begins with well-known criticisms of nonreligious ethics and then develops an atheistic metaethics. In Part 2, Martin criticizes the Christian foundation of ethics, specifically the ’divine command theory’ and the idea of imitating the life of Jesus as the basis of Christian morality. Part 3 demonstrates that life can be meaningful in the absence of religious belief. Part 4 criticizes the theistic point of view in general terms as well as the specific Christian (...) doctrines of the atonement, salvation, and the resurrection. (publisher, edited). (shrink)

Taking issue with those who see recent social transformations as an extension of modernity, the author contends that social theory must confront an epochal change from the modern era to a new era of globality, in which human beings can conceive of forces at work on a global scale, and in which they espouse values that take the globe as their reference point. The book begins by assessing the problems of writing about modernity, showing how narratives of an endlessly self-perpetuating (...) modern age were intrinsic to the "modern project," the attempt by Enlightenment philosophers to transform the everyday world in accord with science and logic under the auspices of the nation-state. Now we are beginning to realize that the nation-state and the modern project cannot renew themselves endlessly through expansion. Instead, the author contends, the age has culminated in its own dissolution, and globality has supplanted modernity as the basis for action and social organization. In theorizing the global age, he considers the worldwide environmental consequences of aggregate human activities, the reconception of human security in the age of nuclear weapons, technological advances in communication systems, the rise of a global economy, and the growing reflexivity of global consciousness, as people and groups begin to refer to the globe as the frame for their beliefs. The book concludes by examining the consequences of the Global Age thesis for politics, identifying a new popular construction of the state that the author terms "performative citizenship." In the modern age, the nation-state was the central power and citizens were beneficiaries of that power, with rights and duties. In the global age, citizens respond to the lack of central power by creating, or performing, the state themselves. The global managerial class uses the skills learned in the bureaucracy of the nation-state to bring pressure on national governments in the interests of global economic, environmental, or human-rights issues. (shrink)

This collection of texts (originally published in German under the title Holzwege) is Heidegger's first post-war book and contains some of the major expositions of his later philosophy. Of particular note are 'The Origin of the Work of Art', perhaps the most discussed of all of Heidegger's essays, and 'Nietzsche's Word 'God is Dead',' which sums up a decade of Nietzsche research. Although translations of the essays have appeared individually in a variety of places, this is the first English translation (...) to bring them all together as Heidegger intended. The text is taken from the last edition of the work, which contains the author's final corrections together with important marginal annotations that provide considerable insight into the development of his thought. This fresh and accurate new translation will be an invaluable resource for all students of Heidegger, whether they work in philosophy, literary theory, religious studies, or intellectual history. (shrink)