Sorting of membrane proteins is generally mediated by cytosolic coats, which create a scaffold to form coated buds and vesicles and to selectively concentrate cargo by interacting with cytosolic signals. The classical paradigm is the interaction between clathrin coats and associated adaptor proteins, which cluster receptors with characteristic tyrosine and dileucine motifs during endocytosis. Clathrin in association with different sets of adaptors is found in addition at the trans-Golgi network and endosomes. Sequences similar to internalization signals also direct lysosomal and (...) basolateral sorting, which implicates related clathrin-adaptor coats in the respective sorting pathways. This review concentrates on the recognition of sorting signals by clathrin-associated adaptor proteins, an area of significant recent progress due to new methodological and conceptual approaches. BioEssays 21:558–567, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

Martin Flashar und Ralf von der Hoff, Die Statue des sog. Philosophen Delphi im Konlexl einer mehrfigurigen Stiftung p. 407-433 Zu den prominentesten Skulpturenfunden in Delphi zâhlt die Statue des sog. Philo sophen (Inv. 1819). Sie fand Aufnahme in die wichtigsten Handbûcher griechischer Plas- tik, obwohl weder Datierung noch Deutung oder gar ursprunglicher Aufstellungszusam- menhang geklàrt sind. Meist wird sie mit stilistischen Argumenten um 250 v. Chr. datiert, ausgelôst durch die hypothetische und falsche Zuweisung an das ebenfalls ungedeutete (...) und undatierte (hâufig aber um die Mitte des 3. Jhs. angesetzte) «Hufeisenmonument» westlich der Daochosgruppe durch L. Lerat. Wie die Neuuntersuchung zeigen kann, ist der « Philosoph » Bestandteil einer mehrfîguren Stiftung gewesen. Die Forschung hat gera- dezu «vergessen», daB er zusammen mit zwei weiteren Statuen, einer weiblichen bekleide- ten (Inv. 1817) und einer ebenfalls langgewandeten mânnlichen (Inv. 1820) gefunden wurde. Technische Indizien belegen den Werkstattzusammenhang, die drei Figuren waren auch zusammen aufgestellt. Sie rechneten zu einer u.U. noch grôBeren (môglicher- weise ist die nackte mànnliche Figur Inv. 1793 zugehôrig) um 300 v. Chr. oder in den ersten Jahrzehnten des 3. Jhs. im Nordsektor des Heiligtums geweihten Gruppe. Das Portràt, der Statuen- und Gewandtypus charakterisieren den « Philosophen » als bûrgerlichen alten Mann — fur die Deutung als wirklicher Philosoph gibt es kein stich- haltiges Argument. Die Frauenfigur lehnt sich ebenfalls an das Darstellungsrepertoire weiblicher Sterblicher (etwa auf attischen Grabreliefs) an. Die dritte Statue bezeugt einen seit dem Strengen Stil gelàufîgen Dionysos-Typus. Als Stifter kommt ein dionysischer Technit oder Chorege in Frage. Auf jeden Fall handelt es sich um ein Familienmonu- ment, das Portràts von mindestens zwei Verwandten prâsentierte und den Gott, dem es geweiht war, in das Ensemble miteinbezog. (shrink)

Multigene delivery and expression systems are emerging as key technologies for many applications in contemporary biology. We have developed new methods for multigene delivery and expression in eukaryotic hosts for a variety of applications, including production of protein complexes for structural biology and drug development, provision of multicomponent protein biologics, and cell‐based assays. We implemented tandem recombineering to facilitate rapid generation of multicomponent gene expression constructs for efficient transformation of mammalian cells, resulting in homogenous cell populations. Analysis of multiple parameters (...) in living cells may require co‐expression of fluorescently tagged sensors simultaneously in a single cell, at defined and ideally controlled ratios. Our method enables such applications by overcoming currently limiting challenges.Here, we review recent multigene delivery and expression strategies and their exploitation in mammalian cells. We discuss applications in drug discovery assays, interaction studies, and biologics production, which may benefit in the future from our novel approach. (shrink)

BackgroundFunctional neurodiagnostics could allow researchers and clinicians to distinguish more accurately between the unresponsive wakefulness syndrome and the minimally conscious state. It remains unclear how it informs surrogate decision-making.ObjectiveTo explore how the next of kin of patients with disorders of consciousness interpret the results of a functional neurodiagnostics measure and how/why their interpretations influence their attitudes towards medical decisions.Methods and SampleWe conducted problem-centered interviews with seven next of kin of patients with DOC who had undergone a functional HD-EEG examination at (...) a neurological rehabilitation center in Germany. The examination included an auditory oddball paradigm and a motor imagery task to detect hidden awareness. We analyzed the interview transcripts using structuring qualitative content analysis.ResultsRegardless of the diagnostic results, all participants were optimistic of the patients’ meaningful recovery. We hypothesize, that participants deal with the results of examinations according to their belief system. Thus, an unfavorable evaluation of the patient’s state had the potential to destabilize the participant’s belief system. To re-stabilize or to prevent the destabilization of their belief system, participants used different strategies. Participants accepted a “positive” HD-EEG result since it stabilized their belief system.ConclusionWe hypothesize, that a group of next of kin of patients with DOC deals with functional neurodiagnostics results on the basis of the result’s value and their high hope that the patient will recover meaningfully. A psychological mechanism seems to moderate the impact of functional neurodiagnostics on surrogate treatment decisions. (shrink)

The allocation of any scarce health care resource, especially a lifesaving resource, can create profound ethical and legal challenges. Liver transplant allocation currently is based upon urgency, a sickest-first approach, and does not utilize capacity to benefit. While urgency can be described reasonably well with the MELD system, benefit encompasses multiple dimensions of patients’ well-being. Currently, the balance between both principles is ill-defined. This survey with 502 participants examines how urgency and benefit are weighted by different stakeholders. Liver transplant patients (...) favored the sickest-first allocation, although all other groups tended to favor benefit. Criteria of a successful transplantation were a minimum survival of at least 1 year and recovery of functional status to being ambulatory and capable of all self-care. An individual delisting decision was accepted when the 1-year survival probability would fall below 50%. Benefit was found to be a critical variable that may also trigger the willingness to donate organs. The strong interest of stakeholder for successful liver transplants is inadequately translated into current allocation rules. (shrink)

Background The allocation of any scarce health care resource, especially a lifesaving resource, can create profound ethical and legal challenges. Liver transplant allocation currently is based upon urgency, a sickest-first approach, and does not utilize capacity to benefit. While urgency can be described reasonably well with the MELD system, benefit encompasses multiple dimensions of patients’ well-being. Currently, the balance between both principles is ill-defined. Methods This survey with 502 participants examines how urgency and benefit are weighted by different stakeholders. Results (...) Liver transplant patients favored the sickest-first allocation, although all other groups tended to favor benefit. Criteria of a successful transplantation were a minimum survival of at least 1 year and recovery of functional status to being ambulatory and capable of all self-care. An individual delisting decision was accepted when the 1-year survival probability would fall below 50%. Benefit was found to be a critical variable that may also trigger the willingness to donate organs. Conclusions The strong interest of stakeholder for successful liver transplants is inadequately translated into current allocation rules. (shrink)

We show that L absoluteness for semi-proper forcings is equiconsistent with the existence of a remarkable cardinal, and hence by [6] with L absoluteness for proper forcings. By [7], L absoluteness for stationary set preserving forcings gives an inner model with a strong cardinal. By [3], the Bounded Semi-Proper Forcing Axiom is equiconsistent with the Bounded Proper Forcing Axiom , which in turn is equiconsistent with a reflecting cardinal. We show that Bounded Martin's Maximum is much stronger than BSPFA (...) in that if BMM holds, then for every X ∈ V , X# exists. (shrink)

The present paper investigates the power of proper forcings to change the shape of the universe, in a certain well-defined respect. It turns out that the ranking among large cardinals can be used as a measure for that power. However, in order to establish the final result I had to isolate a new large cardinal concept, which I dubbed “remarkability.” Let us approach the exact formulation of the problem—and of its solution—at a slow pace.Breathtaking developments in the mid 1980s found (...) one of its culminations in the theorem, due to Martin, Steel, and Woodin, that the existence of infinitely many Woodin cardinals with a measurable cardinal above them all implies that AD, the axiom of determinacy, holds in the least inner model containing all the reals, L. One of the nice things about AD is that the theory ZF + AD + V = L appears as a choiceless “completion” of ZF in that any interesting question seems to find an at least attractive answer in that theory. Beyond that, AD is very canonical as may be illustrated as follows.Let us say that L is absolute for set-sized forcings if for all posets P ∈ V, for all formulae ϕ, and for all ∈ ℝ do we have thatwhere is a name for the set of reals in the extension. (shrink)

Der große jüdische Religionsphilosoph Martin Buber (1878-1965) war auch als Pädagoge und Andragoge eine bedeutende Persönlichkeit in der Geistesgeschichte des 20. Jahrhunderts. 1924 war er Gast der damals von Wilhelm Flitner geleiteten Volkshochschule Jena. An seinen dortigen Begegnungen lässt sich exemplarisch das Selbstverständnis und die Methodik Bubers eindrucksvoll sichtbar machen. Von der Analyse der Jenaer Konstellation geht dieser Sammelband aus, führt aber darüber hinaus zu Bubers weitgespannten Wirkungsfeldern, wobei auch bisher unerschlossenes Archivmaterial ausgewertet wird. Vertieft werden neben pädagogisch-andragogischen auch (...) religiöse, sprachanalytische und politisch-ethische Aspekte, dargestellt u.a. auch über biographische Bezüge zu herausragenden Zeitgenossen wie Leo Boeck und Dag Hammarskjöld. Darüberhinaus enthält der Band auch Unveröffentlichtes aus Bubers Feder, so eine Auswahl aus seinem Briefwechsel mit Wilhelm Flitner sowie einen systematischen Grundlagenartikel zur Erwachsenenbildung. (shrink)

The conference in a nutshell: philosophy in times of crises returned to a crisis in philosophy. The pandemic throws us back on our feet and makes us rethink the question raised at the Davos Disputation between Martin Heidegger and Ernst Cassirer in 1929: “What is a human being?” While both had agreed that the initial question was the crucial question to tackle, neither of them could put forth a solution to the question given that their own thought paths proved (...) to have led them into a dead end and to the necessity to turn in a new direction in order to overcome a philosophical crisis. So, in 2020, why not move beyond the scope of this German–German disputation in Davos, and even beyond the horizon of Europe to look for new pathways of thought? (shrink)

We show that if I is a precipitous ideal on ω₁ and if θ > ω₁ is a regular cardinal, then there is a forcing P = P(I, θ) which preserves the stationarity of all I-positive sets such that in $V^P $ , is a generic iterate of a countable structure . This shows that if the nonstationary ideal on ω₁ is precipitous and $H_\theta ^\# $ exists, then there is a stationary set preserving forcing which increases $\delta _2^1 $ (...) · Moreover, if Bounded Martin's Maximum holds and the nonstationary ideal on ω₁ is precipitous, then $\delta _2^1 $ = u₂ = ω₂. (shrink)

The famous debate between Ernst Cassirer and Martin Heidegger of 1929 in Davos was set on a global stage and, yet, inherently Eurocentric. This volume explores how the hypothetical presence of the Kyoto school founder Nishida Kitarō would have overcome this limitation.

We isolate natural strengthenings of Bounded Martin’s Maximum which we call ${\mathsf{BMM}}^{*}$ and $A-{\mathsf{BMM}}^{*,++}$, and we investigate their consequences. We also show that if $A-{\mathsf{BMM}}^{*,++}$ holds true for every set of reals $A$ in $L$, then Woodin’s axiom $$ holds true. We conjecture that ${\mathsf{MM}}^{++}$ implies $A-{\mathsf{BMM}}^{*,++}$ for every $A$ which is universally Baire.

This book presents the first collection of essays on the philosophy of Ueda Shizuteru in a Western language. Ueda, the last living member of the Kyoto school, has fostered the East-West dialogue in all his works and has helped to open up the Western image of philosophy by engaging the Zen tradition. The book reflects this particular trait of Ueda’s philosophy, but it also covers all thematic fields of his writings. Contributions from both young and established scholars and experts from (...) Japan, Europe and the U.S. make this a unique introduction to and reception of Ueda’s philosophy. Readers will discover discussions of mysticism in the East and West, and consideration of modern philosophy topics including self-awareness, nature and poetic language. The book also presents a focussed look at language and nothingness, considering silence and nihilism. Chapters allow the reader to understand the timeliness of a thinking that mediates and transcends the dichotomy of East and West. This volume will appeal not only to scholars of Nishida, Japanese philosophy, mysticism and religious experience in Japan, but also to scholars of Western philosophy, especially those interested in Meister Eckhart, Martin Heidegger and Martin Buber. It makes an ideal introduction to Zen philosophy and presents important contributions to scholarship on language and experience. (shrink)

Angesichts von Zweifel und Verzweiflung, von Furcht und Angst - jeweils verstanden als existentielle Grundbefindlichkeiten des Menschen - werden Haltungen gelingenden Lebens gesucht. Die Ethik bietet Tugenden als Wege zu einer gelingenden Lebensfuhrung an. Die Beitrager dieses Buches suchen nach Entwurfen, die die Verbindung des Tugendgedankens mit dem naturlichen Glucksverlangen des Menschen zu ermoglichen helfen und erortern, welche Bedeutung dabei Mut, Gelassenheit und Weisheit zukommt. Dabei werden ideengeschichtliche Entwurfe in heutigen Problemkontexten auf ihre Gultigkeit hin gepruft. Mit Beitragen von (...) class='Hi'>Martin Ebner, Markus Enders, Friedrich-Wilhelm von Herrmann, Stephan Herzberg, Hubert Irsigler, Margit Kopper, Matthias Kossler, Jean-Luc Marion, Peter Reifenberg, Ralf Rothenbusch, Gerd Theissen, Klaus Viertbauer und Gunther Wenz. (shrink)

Gustav Radbruch war Deutschlands beruhmtester Rechtsphilosoph im 20. Jahrhundert. Seine gehaltvollen, aber auch spannungsreichen Schriften pragen die deutschsprachige Rechtsphilosophie bis heute. Im Zentrum von Radbruchs Lehre steht sein neukantianisch gepragter Rechtsbegriff, der im Laufe der Zeit eine Reihe von Veranderungen erfahren hat. Die Beitrage in diesem Band sind Radbruchs Rechtsbegriff im Allgemeinen und den Wandlungen dieses Rechtsbregriffs im Besonderen gewidmet. Nach der orthodoxen Lesart vertrat Radbruch vor dem Kriege eine rechtspositivistische Lehre, wurde unter dem Eindruck der nationalsozialistischen Grauel jedoch zum (...) Naturrecht bekehrt. Zunehmend wird gesehen, dass diese 'Bekehrungsthese' zu Ungereimtheiten fuhrt. Verschiedene Beitrage dieses Bandes betonen demgegenuber die Kontinuitat nichtpositivistischer Elemente in der Entwicklung von Radbruchs Rechtsbegriff. Mit Beitragen von: Hidehiko Adachi, Martin Borowski, Horst Dreier, Ralf Dreier, An dreas Funke, Ulfrid Neumann, Stanley L. Paulson, Joachim Renzikowski, Hubert Rottleuthner, Marc Andre Wiegand. (shrink)

Peter Abelard (1079–1142 ce) was the most wide‐ranging philosopher of the twelfth century. He quickly established himself as a leading teacher of logic in and near Paris shortly after 1100. After his affair with Heloise, and his subsequent castration, Abelard became a monk, but he returned to teaching in the Paris schools until 1140, when his work was condemned by a Church Council at Sens. His logical writings were based around discussion of the “Old Logic”: Porphyry's Isagoge, aristotle'S Categories and (...) On Interpretation and boethius'S textbook on topical inference. They comprise a freestanding Dialectica (“Logic”; probably c.1116), a set of commentaries (known as the Logica [Ingredientibus], c. 1119) and a later (c. 1125) commentary on the Isagoge (Logica Nostrorum Petititoni Sociorum or Glossulae). In a work Abelard called his Theologia, issued in three main versions (between 1120 and c.1134), he attempted a logical analysis of trinitarian relations and explored the philosophical problems surrounding God's claims to omnipotence and omniscience. The Collationes (“Debates,” also known as “Dialogue between a Christian, a Philosopher and a Jew”; probably c.1130) present a rational investigation into the nature of the highest good, in which the Christian and the Philosopher (who seems to be modeled on a philosopher of pagan antiquity) are remarkably in agreement. The unfinished Scito teipsum (“Know thyself,” also known as the “Ethics”; c.1138) analyses moral action. (shrink)

ABSTRACTOne prestudy based on a corpus analysis and four experiments in which participants had to invent novel names for persons or objects investigated how the valence of a face or an object affects the phonological characteristics of the respective novel name. Based on the articulatory feedback hypothesis, we predicted that /i:/ is included more frequently in fictional names for faces or objects with a positive valence than for those with a negative valence. For /o:/, the pattern should reverse. An analysis (...) of the Berlin Affective Word List – Reloaded yielded a higher number of occurrences of /o:/ in German words with negative valence than in words with positive valence; with /i:/ the situation is less clear. In Experiments 1 and 2, participants named persons showing a positive or a negative facial expression. Names for smiling persons included more /i:/s and fewer /o:/s than names for persons with a negative facial expression. In Experiments 3 and 4, participant... (shrink)

In this lively collection ten philosophers tackle the notoriously elusive issues raised by religious discourse in a series of linked debates. The debates focus on reason and faith; the logic of mysticism; the meaning of the word 'God'; language, biblical interpretation and worship; and religion and ethics. Through contemporary philosophical analysis it is possible to shed new light on teh status and language of religion, and in many ways the contributors to Religion and Philosophy break new ground in this perennially (...) controversial field. The collection is addressed to philosophers, theologians and anyone with a general intellectual interest in religion. Certainly it will be a valuable addition to the reading list of all teachers or students of the philosophy of religion. (shrink)

Martin Wrights original ground-breaking and influential analysis of the defects of the adversarial system of justice, plus the arguments in favour of a more ...

Inductive Metaphysics combines an anti-aprioristic emphasis on an empirical and scientific basis for metaphysics with an insistence on a specifically philosophical abductive theory-building. Since the latter specifically philosophical work is not empirical itself, it may in a liberal sense be called apriori. This paper highlights this apriori dimension within IM by a case study on Structuralism, the view that fundamental reality consists of a network of relations, which a number of philosophers consider to be suggested by modern physics. Focussing on (...) Dasgupta’s algebraic Generalism, the author argues that Structuralism suffers from a severe entailment problem, because the relations-spanning apparatus must stand for metaphysically fundamental forms. Schaffer’s contention that there are no entailment problems is rejected. Advocates of IM are well advised to take seriously their own insistence on metaphysical abduction and not to one-sidedly emphasise the empirical input: the elaboration of exact metaphysical theories and the apriori evaluation of their inherent tenability is a constituent of IM no less important than the consideration of scientific input. More traditional ways of metaphysical reasoning inevitably survive as an essential dimension within IM. (shrink)

Heidegger in America explores the surprising legacy of his life and thought in the United States of America. As a critic of modern life, Heidegger often lamented the growing global influence of all things American. However, it was precisely in America where his thought inspired the work of generations of thinkers – not only philosophers but also theologians, architects, novelists, and even pundits. As a result, the reception and dissemination of Heidegger's philosophical writings transformed the intellectual and cultural history of (...) the United States at a time when American influence was itself transforming the world. A case study in the complex and sometimes contradictory process of transnational exchange, Heidegger in America recasts the scope and methods of contemporary intellectual and cultural history in the age of globalization, challenging what we think we know about Heidegger and American ideas simultaneously. (shrink)

Strong dispositional monism, the position that all fundamental physical properties consist in dispositional relations to other properties, is naturally construed as property structuralism. J. Lowe’s circularity/regress objection constitutes a serious challenge to SDM that questions the possibility of a purely relational determination of all property essences. The supervenience thesis of A. Bird’s graph-theoretic asymmetry reply to CRO can be rigorously proved. Yet the reply fails metaphysically, because it reveals neither a metaphysical determination of identities on a purely relational basis nor (...) a determination specifically of identities in the sense of essences. Asymmetry is thus not by itself sufficient for a solution to CRO. But it cannot even help to answer CRO when a model for the determination of essences is taken as a basis. Nor is asymmetry necessary for a reply, as property structures may well be symmetric. A metaphysics of dispositional properties as grounded in a purely relational structure faces serious obstacles, and the properties would not be fundamental. Since essence and grounding are notions of metaphysical priority, there can be no essentially dispositional metaphysically fundamental properties, and the prospects of a “coherentist” metaphysics of basic properties are dim. A modal retreat that refrains from a post-modal conception of essence and simply claims that fundamental properties play dispositional roles by metaphysical necessity is unsatisfactory. (shrink)

The mechanics of claims focusses predominantly on the claim to life. The claim to life is rooted in the autonomy principle, just like other specific claims. Still, the mechanics of claims does not have a systematic place for the fundamental negation of the status as an autonomous being as such. It is, however, the proctiction of the status as such, which is at the center of the protection of human dignity in German constitutional law. Looked at it from this perspective, (...) the protection of human dignity as the protection of the status of an autonomous human being, appears to be a blind spot of the mechanics of claims. The comment attempts to show, how this blindspot leads to inconsistencies in the mechanics of claims, and how they might be ameliorated if human dignity is considered as an absolute right independent of the claims to life. (shrink)