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)

A complete English translation of the correspondence between the philosopher Martin Heidegger and the novelist and essayist Ernst Jünger, together with a translation of Jünger’s essay Across the Line.

Evolutionary change is opportunistic, but its course is strongly constrained in several fundamental ways. These constraints (historical/phylogenetic, functional/adaptive, constructional/morphogenetic) and their dynamic relationships are discussed here and shown to constitute the conceptual framework of Constructional Morphology. Notwithstanding recent published opinions which claim that the discovery of constraints renders Neodarwinian selection theory obsolete, we regard the insights of Constructional Morphology as being entirely consistent with this theory. As is shown here in the case of the Hyracoidea, formal analysis of the constraints (...) which have framed the evolution of various characters extends our understanding of the evolution of a taxon. (shrink)

Almost two decades ago, Prahalad and Hammond [Harv Bus Rev, 80(9):48–59, 2002] introduced the base/bottom of the pyramid (BOP) approach to profitably serving the poor with business models adapted from developed markets while alleviating poverty. In response to disappointing results and ethical criticism, the BOP approach evolved from a just-for-profit approach with a passive role of the poor to an inclusive development approach that integrates the principles of the triple bottom line. A recent review of the BOP literature [Dembek et (...) al., J Bus Ethics 165(3):365–382, 2020], however, reveals a lack of empirical evidence to support the sustainable BOP approach. In this paper, we specify the assumptions underlying the sustainable BOP approach and test them using structural equation modeling with clustered robust standard errors on a unique dataset of 212 firms. Our findings show that BOP business model involvement and adaptive capacity are significant drivers of the triple bottom line at the BOP; however, business model adaptive capacity does not guarantee an ecologically sustainable performance at the BOP. We find that there is a need for further extension of the ethical foundations of the sustainable BOP approach. (shrink)

Die Autoren berichten über die erste kontrollierte Psychotherapiestudie, die psychoanalytische und kognitiv-verhaltenstherapeutische Langzeitpsychotherapien mit randomisierter und präferierter Zuweisung mit­einander vergleicht. In vier Behandlungszentren wurden 554 chronisch depressive Patienten interviewt, von denen 252 in die Studie aufgenommen werden konnten. In den Selbsteinschätzungen der Patienten zeigten sich große und stabile Veränderungen. Die vollständige Remissionsrate (für BDI) lag nach einem Jahr bei 34 % und stieg auf 45 % nach drei Jahren. Analoge Ergebnisse zeigten sich in den Einschätzungen der unabhängigen, bezogen auf die (...) Therapieverfahren verblindeten Rater (QIDS). Entgegen ihrer Hypothesen fanden die Autoren aber keinen statistisch signifikanten Unterschied zwischen den Verfahren und auch keine Effektunterschiede zwischen randomisierter Therapiezuweisung und Behandlung mit der präferierten Psychotherapie. Besser als in anderen Studien sind die erzielten Remissionsraten, die zeigten, dass chronisch depressive Patienten von Langzeitpsychotherapien profitieren. (shrink)

Ernst Cassirer occupies a unique space in Twentieth-century philosophy. A great liberal humanist, his multi-faceted work spans the history of philosophy, the philosophy of science, intellectual history, aesthetics, epistemology, the study of language and myth, and more. Cassirer's thought also anticipates the renewed interest in the origins of analytic and continental philosophy in the Twentieth Century and the divergent paths taken by the 'logicist' and existential traditions, epitomised by his now legendary debate in 1929 with the philosopher Martin (...) Heidegger, over the question "What is the Human Being?" The Philosophy of Symbolic Forms is Cassirer's most important work. It was first published in German in 1923, the third and final volume appearing in 1929. In it Cassirer presents a radical new philosophical worldview - at once rich, creative and controversial - of human beings as fundamentally "symbolic animals," placing signs and systems of expression between themselves and the world. This major new translation of all three volumes, the first for over fifty years, brings Cassirer's magnum opus to a new generation of students and scholars. Taken together, the three volumes of The Philosophy of Symbolic Forms are a vital treatise on human beings as symbolic animals and a monumental expression of neo-Kantian thought. Correcting important errors in previous English editions, this translation reflects the contributions of significant advances in Cassirer scholarship over the last twenty to thirty years. Each volume includes a new introduction and translator's notes by S. G. Lofts, a foreword by Peter Gordon, a glossary of key terms, and a thorough index. (shrink)

BackgroundBiobanking biospecimens and consent are common practice in paediatric research. We need to explore children and young people’s (CYP) knowledge and perspectives around the use of and consent to biobanking. This will ensure meaningful informed consent can be obtained and improve current consent procedures.MethodsWe designed a survey, in co-production with CYP, collecting demographic data, views on biobanking, and consent using three scenarios: 1) prospective consent, 2) deferred consent, and 3) reconsent and assent at age of capacity. The survey was disseminated (...) via the Young Person’s Advisory Group North England (YPAGne) and participating CYP’s secondary schools. Data were analysed using a qualitative thematic approach by three independent reviewers (including CYP) to identify common themes. Data triangulation occurred independently by a fourth reviewer.ResultsOne hundred two CYP completed the survey. Most were between 16–18 years (63.7%, N = 65) and female (66.7%, N = 68). 72.3% had no prior knowledge of biobanking (N = 73).Acceptability of prospective consent for biobanking was high (91.2%, N = 93) with common themes: ‘altruism’, ‘potential benefits outweigh individual risk’, 'frugality', and ‘(in)convenience’.Deferred consent was also deemed acceptable in the large majority (84.3%, N = 86), with common themes: ‘altruism’, ‘body integrity’ and ‘sample frugality’. 76.5% preferred to reconsent when cognitively mature enough to give assent (N = 78), even if parental consent was previously in place. 79.2% wanted to be informed if their biobanked biospecimen is reused (N = 80).ConclusionProspective and deferred consent acceptability for biobanking is high among CYP in the UK. Altruism, frugality, body integrity, and privacy are the most important themes. Clear communication and justification are paramount to obtain consent. Any CYP with capacity should be part of the consenting procedure, if possible. (shrink)

Eu creio que devemos agradecer a Heidegger por nos ter claramente colocado, diante de nossos olhos, o verdadeiro “acontecimento” filosófico, que se consuma na fundamentação da filosofia de Kant, de modo que tal acontecimento torna-se visível na totalidade de sua força interna e em seu ímpeto. Mas, me parece que ele não percorreu a totalidade da esfera da problemática do “idealismo transcendental”.

Normal 0 21 In 1802 Hegel publishes in Jena “On the Relationship of Skepticism to Philosophy”. This article has the objective of criticizing the skepticism of Gottlob Ernst Schulze. The accomplishment of that critic will demand from Hegel the review of some fundamental aspects of the ancient skepticism. It treats here of reconsidering Hegel’s interpretation of the ancient skepticism, starting from that critic to the modern skepticism of Schulze.

Article Punt, Jozef: Die Idee der Menschenrechte. Ihre geschichtliche Entwicklung und ihre Rezeption durch die moderne katholische Sozialverkündigung Böckenförde, Ernst, Wolfgang und Spaemann, Robert (Hg.): Menschenrechte und Menschenwürde. Historische Voraussetzungen - säkulare Gestalt - christliches Verständnis was published on February 1, 1989 in the journal Zeitschrift für Evangelische Ethik (volume 33, issue 1).

Ernst Cassirer est un philosophe juif allemand, contemporain de la Seconde Guerre mondiale. Auteur majeur pour l'histoire de la pensée occidentale, il est cependant resté dans l'ombre de Heidegger pendant de nombreuses années. Sa philosophie, centrée sur la question de la culture et du politique, trouve dans la forme symbolique du mythe une explication à la naissance du totalitarisme. Dans une démarche critique, Cassirer analyse l'apparition du mythe totalitaire en Allemagne comme une crise culturelle ayant engendré par la suite (...) une crise morale et politique. Cette crise culturelle trouve sa source au sein du courant romantique allemand, dont les mauvaises interprétations – ou réutilisations – par les idéologues nazis ont conduit aux dérives nationalistes et au culte du héros. À la pensée mythique, Cassirer oppose la pensée libre, éclairée et critique, seule voie de sortie possible selon lui pour dépasser le mythe totalitaire. « Sapere aude! », selon la formule kantienne : osons penser! Ayons le courage de nous servir de notre propre entendement. (shrink)

Growing interest has been shown toward humanism in the 21st century after decades of critique and rejection. Posthumanism and transhumanism have redefined the topic primarily through developments in technology and by focusing on relations of interconnectedness between humans and the environment. A different concern with ‘being human’ can be found in the writings of Zygmunt Bauman and Ernst Bloch. The leitmotif of Bauman’s sociology and of Bloch’s utopian philosophy is their assertion that humans have the distinct capacity to transcend (...) necessity and inevitability. Their works share the concern for a good society that would ameliorate social fragmentation and disintegration. Following this, the article seeks to theorize the meaning of humanism in the contemporary era. Taking up Bauman’s notion of interregnum, the article will argue that the contemporary importance of humanism is social in the sense of redeeming the currently casualized human condition, i.e. diminished life-chances, inequality and alienation. Interregnum marks a historical epoch where the old order has decayed, but the new one is not yet present. In interregnum, or in what Bloch calls Mischzeit, humanism is about a human being-in-the-world which contains the possibility to do better. (shrink)

--Prophet mit Marx- und Engelszungen, von M. Walser.--Philosophie zwischen Traum und Apokalypse, von I. Frenzel.--Messianismus und Marxismus, von J. Moltmann.--Ein marxistischer Schelling, von J. Habermas.--Ein Gespräch über ungelöste Aufgaben der sozialistischen Theorie, von E. Bloch und F. Vilmar.--Ein grosser Einzelgänger, von I. Fetscher.--Ernst Blochs Evolution des Marxismus, von W. Maihofer.--Ausgewählte Bibliographie der Schriften über Ernst Bloch, zusammengestellt von R. Kübler (p. 133-[149]).

Der Skeptizismus ist der advocatus diaboli der Philosophie. Welche Immunisierungsstrategien fand man gegen ihn? Zu den spannenden und lehrreichen Facetten des Deutschen Idealismus gehört zweifelsohne die mit der Auseinandersetzung mit Kants kritizistischer Position anhebende Debatte um einen neuen Skeptizismus. Von ausserordentlichem Interesse bleibt hierbei der Gehalt der Repliken Reinholds, Fichtes und Hegels auf die Attacken von Gottlob Ernst Schulze. Aus heutiger Perspektive geht es um die philosophische Relevanz und Stringenz der verschiedenen Immunisierungsstrategien gegen den Skeptizismus. Der Band widmet sich (...) den philosophischen Voraussetzungen, systematischen Aspekten und Kontexten der Angriffe Schulzes auf Reinhold, sowie den Auswirkungen dieser zum Teil neu zugespitzten Angriffe bei Fichte, Hegel u.a. (shrink)

RÉSUMÉ: Cet article questionne la relation de pensée entre Martin Heidegger et Ernst Jünger. Pour comprendre les motifs philosophiques qui la sous-tendent, nous situons Jünger dans la reconstruction heideggérienne de la métaphysique. On s’aperçoit alors que Heidegger mesure la pensée de Jünger en fonction de la place de Nietzsche dans l’histoire de la philosophie. Parce que Jünger appartient au paradigme nietzschéen, Heidegger le juge digne d’être lu, et critiqué, car Jünger n’a pas accompli le projet que Nietzsche a (...) rendu possible en signant l’achèvement de la métaphysique. C’est ce projet que Heidegger a adapté, en menant la pensée philosophique par-delà la métaphysique et en espérant un renouveau civilisationnel de l’Allemagne. Nietzsche se présente comme le pôle central de la relation entre Heidegger et Jünger: à travers sa lecture critique de Jünger, Heidegger mène un dialogue ininterrompu avec Nietzsche.ABSTRACT: This article investigates Martin Heidegger’s intellectual relation to Ernst Jünger. In order to show that Heidegger’s appraisal of Jünger is directly related to his understanding of Nietzsche’s pre-eminent standing in the history of Western philosophy, I situate Jünger in the Heideggerian reconstruction of the history of metaphysics. It is because Jünger belongs to the Nietzschean paradigm that Heidegger believes he is worth reading-but also worth criticizing Indeed, Jünger did not overtake the philosophical project that Nietzsche made possible by accomplishing the end of metaphysics. This is the very project adopted by Heidegger, first by thinking beyond metaphysics, and second by hoping Germany would turn towards a spiritual renewal of its civilization. Thus, since Nietzsche is the central figure who stands between Heidegger and Jünger, this article wishes to show that through his critical reading of Jünger, Heidegger in fact fosters a fundamental and uninterrupted dialogue with Nietzsche. (shrink)

RÉSUMÉ: Cet article questionne la relation de pensée entre Martin Heidegger et Ernst Jünger. Pour comprendre les motifs philosophiques qui la sous-tendent, nous situons Jünger dans la reconstruction heideggérienne de la métaphysique. On s’aperçoit alors que Heidegger mesure la pensée de Jünger en fonction de la place de Nietzsche dans l’histoire de la philosophie. Parce que Jünger appartient au paradigme nietzschéen, Heidegger le juge digne d’être lu, et critiqué, car Jünger n’a pas accompli le projet que Nietzsche a (...) rendu possible en signant l’achèvement de la métaphysique. C’est ce projet que Heidegger a adapté, en menant la pensée philosophique par-delà la métaphysique et en espérant un renouveau civilisationnel de l’Allemagne. Nietzsche se présente comme le pôle central de la relation entre Heidegger et Jünger: à travers sa lecture critique de Jünger, Heidegger mène un dialogue ininterrompu avec Nietzsche.ABSTRACT: This article investigates Martin Heidegger’s intellectual relation to Ernst Jünger. In order to show that Heidegger’s appraisal of Jünger is directly related to his understanding of Nietzsche’s pre-eminent standing in the history of Western philosophy, I situate Jünger in the Heideggerian reconstruction of the history of metaphysics. It is because Jünger belongs to the Nietzschean paradigm that Heidegger believes he is worth reading-but also worth criticizing Indeed, Jünger did not overtake the philosophical project that Nietzsche made possible by accomplishing the end of metaphysics. This is the very project adopted by Heidegger, first by thinking beyond metaphysics, and second by hoping Germany would turn towards a spiritual renewal of its civilization. Thus, since Nietzsche is the central figure who stands between Heidegger and Jünger, this article wishes to show that through his critical reading of Jünger, Heidegger in fact fosters a fundamental and uninterrupted dialogue with Nietzsche. (shrink)

RÉSUMÉ: Cet article questionne la relation de pensée entre Martin Heidegger et Ernst Jünger. Pour comprendre les motifs philosophiques qui la sous-tendent, nous situons Jünger dans la reconstruction heideggérienne de la métaphysique. On s’aperçoit alors que Heidegger mesure la pensée de Jünger en fonction de la place de Nietzsche dans l’histoire de la philosophie. Parce que Jünger appartient au paradigme nietzschéen, Heidegger le juge digne d’être lu, et critiqué, car Jünger n’a pas accompli le projet que Nietzsche a (...) rendu possible en signant l’achèvement de la métaphysique. C’est ce projet que Heidegger a adapté, en menant la pensée philosophique par-delà la métaphysique et en espérant un renouveau civilisationnel de l’Allemagne. Nietzsche se présente comme le pôle central de la relation entre Heidegger et Jünger: à travers sa lecture critique de Jünger, Heidegger mène un dialogue ininterrompu avec Nietzsche.ABSTRACT: This article investigates Martin Heidegger’s intellectual relation to Ernst Jünger. In order to show that Heidegger’s appraisal of Jünger is directly related to his understanding of Nietzsche’s pre-eminent standing in the history of Western philosophy, I situate Jünger in the Heideggerian reconstruction of the history of metaphysics. It is because Jünger belongs to the Nietzschean paradigm that Heidegger believes he is worth reading-but also worth criticizing Indeed, Jünger did not overtake the philosophical project that Nietzsche made possible by accomplishing the end of metaphysics. This is the very project adopted by Heidegger, first by thinking beyond metaphysics, and second by hoping Germany would turn towards a spiritual renewal of its civilization. Thus, since Nietzsche is the central figure who stands between Heidegger and Jünger, this article wishes to show that through his critical reading of Jünger, Heidegger in fact fosters a fundamental and uninterrupted dialogue with Nietzsche. (shrink)

The present analysis of the evolution of the concept of freedom in Ernst Tugendhat’s philosophy aims to highlight several interesting facts. First, Tugendhat attempts to describe the meaning of Kant’s statement “I could have acted otherwise” from a non-transcendental perspective. Second, he makes an effort to avoid the classical Kantian dilemma of the relation of free will and determinism by posing the question differently. Third, he situates the issue of the relation of freedom and causality in the framework of (...) the inner structure of freedom – examining it from the perspective of the human’s relation to him- or herself. Fourth, he attempts repeatedly to overcome the impossibility of considering freedom in the objective language of causality. The paper demonstrates why the issue of freedom remains a central problem of continental philosophy. (shrink)

"Exemplary Originality": Kant on Genius and Imitation MARTIN GAMMON 1. INTRODUCTION ACCORDING TO ERNST CASSIRER, Kant 's discussion of genius in the Third Cri- tique stands "at the crossroads of all aesthetic discussions in the eighteenth century," in that he tries to accommodate the neo-Classical demand that art- works follow determinate rules to the Romantic insistence that aesthetic cre- ativity be free from such rules? In the Third Critique itself, Kant defends both of these criteria through the doctrine (...) of "exemplary originality." For Kant, the genius combines two qualities: on the one hand, "a talent for produc- ing that for which no rule can be given," so that "originality must be its primary property"; however, "since there may also be original nonsense, its products must at the same time be models, i.e., be exemplary; and consequently, though not themselves derived from imitation, they must serve that purpose for oth- ers, i.e., as a standard or rule for estimating."' On the basis of this exemplary originality, then, a genius puts "freedom from constraint of rules so into force in his art, that for art itself a new rule is won -- which is what shows a talent to be exemplary". Recently, some commentators have puzzled over the "air of paradox" sur- rounding Kant 's union of originality and exemplarity in works of genius. "If such works," Timothy Gould conjectures, "make advances on what is familiar and gain new ground, their very. (shrink)

The aim is to examine Alois Riehl’s contribution to the “culture war” (Kulturkampf) in the second half of the nineteenth century. We show that he used Kant’s autonomy principle to argue against the idea that religious dogmatism is a fundament of morality. We prove this thesis by focusing on the forgotten historical background, which is important for an understanding of Morals und Dogma. Originally this essay was an expert opinion for the court case of the socialist H. Tauschinski who was (...) accused of blasphemy. Tauschinski wrote an article in which he doubted the immortality of the soul and the existence of a personal God. These two dogmas of the Catholic Church were considered bу the Austrian authorities to be the foundations of public order. Riehl questioned not only the charge but also the validity of religious dogmas for morality. Based on Kant’s ethics, he argued for a moral indifferentism of religious dogmas. His career was significantly influenced by this essay, because of its anti-clerical content. During the culture war, Riehl repeatedly had problems with the authorities, especially in the Austro-Hungarian monarchy. The “Neurath-Haller Thesis” argues that in Austria the appointment of professorships was controlled and monitored by the state, with the goal of installing a philosophy which was beneficial to the interests of the state, and a strong anti-Kantianism in Austrian Philosophy as a consequence. We can agree with this thesis insofar as Riehl in the period of the “Catholic Renaissance” in Austria was not allowed to succeed Ernst Mach. The analysis of Riehl’s arguments allows us furthermore to understand Riehl as a neo-Kantian as early as 1871/1872, which has been questioned by many authors who think the early Riehl was no Kantian. (shrink)