Binding of a growth factor (GF) to its specific receptor on the cell surface causes the initiation of a signal transduction cascade which eventually results in mitosis. GF:receptor complexes are removed from the cell surface via receptor‐mediated endocytosis, a process which involves clathrin‐coated pits. After internalization into the endosomal compartment, a significant pool of GFs and GF receptors escape recycling to the cell surface and are sorted to the degradation pathway. The ligandinduced internalization and lysosomal degradation of GF receptors result (...) in the dramatic loss of surface receptors, a phenomenon termed receptor down‐regulation. In this review, we discuss relevant biochemical, morphological and kinetic studies of the mechanism of GF endocytosis, and the possible role of this process in mitogenic signaling by growth factor receptors. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Journal of the History of Ideas 63.1 (2002) 83-104 [Access article in PDF] Reluctant Modernism: Moses Mendelssohn's Philosophy of History Matt Erlin In a well-known passage from the second section of Jerusalem (1784) Moses Mendelssohn takes his old friend Lessing to task for his recent treatise on The Education of the Human Race (1780). His respect for the author notwithstanding, Mendelssohn has little sympathy for Lessing's view of human (...) progress. Opposing the attempt to force the entire species into a single framework of linear development, Mendelssohn claims that, as a species, humankind has always oscillated between cultivation and barbarism. Borrowing the "ages of man" metaphor that Lessing employed in his own discussion, he writes that at almost any point in human history, man is "child, adult, and old man at the same time, though in different places and regions of the world." 1 Against Lessing's concept of global progress Mendelssohn proposes a model in which each individual follows his own trajectory of self-cultivation, a trajectory that begins before birth, intersects more or less briefly with the plane of historical time, and then continues after death into eternity.Mendelssohn's resistance to the Geschichtsphilosophie articulated here by Lessing and later appropriated by Kant, Schiller, and Hegel has been subject to a variety of interpretations. Not surprisingly, more recent commentators have stressed the philosopher's defense of particularity, his opposition to a totalizing theory of history that threatens to grant the individual nothing more than a bit part in the realization of some future state of human perfection. Norbert Hinske, for example, has argued that Mendelssohn's late writings engage in a conscious confrontation with Kant's understanding of historical progress. 2 [End Page 83]According to Hinske, especially Mendelssohn's short text On the Ideal Constitution indicates that the author "must have recognized spontaneously that Kant's proposed solution, whether intentionally or unintentionally, degraded the individual to a mere means of social progress...." 3Mendelssohn's concern for the individual is certainly central to his rejection of a species-based historical teleology, but one should also keep in mind the ethnic and cultural implications of such a model. As both Kant's and Hegel's later writings reveal, any attempt to understand human history in terms of a coherent, linear narrative, especially one that culminates in the rise of Christian Europe, is necessarily troubled by the continued existence of Judaism. In other words it is not just the individual who suffers an implicit reduction in status in late eighteenth-century theories of progress; entire cultures become vestigial once their historical function has been fulfilled. 4 Although the texts containing the most striking hostility toward Judaism were published after the appearance of Jerusalem, a somewhat surprising anti-Jewish bias is already evident in Lessing's explorations of the topic. Lessing does after all refer to the Jews in the period of Egyptian exile as "the most rude and the most ferocious" people imaginable. 5 Moreover, although he grants them a crucial role as educators of humanity, this role lasts only until the appearance of Jesus Christ, an event that simultaneously marks the end of the childhood of humankind. As Hans Liebeschütz has remarked, Lessing's adoption of this position must have been quite a blow to Mendelssohn. 6Each of these reasons for Mendelssohn's skepticism is significant in its own right; taken together, they also raise fundamental questions regarding his relationship to modernity and modern historical consciousness more generally. In one respect, of course, the topic of Mendelssohn's modernity has been much debated. Ever since Alexander Altmann's 1973 biography addressed the philosopher's complex relation to the "two disparate worlds of Judaism and modern Enlightenment," scholars have sought to untangle the strands of tradition and innovation in his work. 7 Most recently, Allan Arkush has depicted Mendelssohn as a radical deist whose observance of Jewish law was largely [End Page 84] strategic, while David Sorkin has emphasized the more conservative aims of his long neglected Hebrew works. 8In light of this interest... (shrink)

This paper argues that specific phobia is an ideal kind of psychiatric disorder because it bears the marks of a mature medical diagnosis and is amenable to causal explanation. A new and ambitious program of ‘causal revolution’ has recently emerged in psychiatry that hopes to refurnish our taxonomies by discovering the underlying biological and psychological causes that create and maintain mental illness. I show that the sort of causal story envisioned by the program is a mechanistic property cluster (MPC) structure, (...) which involves a causal mechanism that explains the co-occurrence of a disorder’s signs and symptoms (Kendler, Zachar & Craver, 2011). I then build a model of fear in humans and sketch a novel account of specific phobia as a configuration of the fear system in thrall to deregulated network dynamics such as hysteresis, tipping points, and feedback loops. Specific phobia has an MPC structure. I close by reflecting on whether we can reasonably expect other mental disorders to fit an MPC mold, and thus lend themselves to future causal validation. This paper shows that specific phobia holds a unique place in our picture of mental disorder that has so far been missed. It is an ideal kind of psychopathology. (shrink)

Seit dem 2. nachchristlichen Jahrhundert werden die Schriften von Aristoteles kommentiert. Diese Ausgabe enthält griechische Kommentare zu seinem Werk vom 3. bis 8. Jahrhundert n. Chr., u. a. von Alexander von Aphrodiensias, Themistios, Joh. Philoponus, Simplicius in griechischer Sprache.

This chapter contains sections titled: Introduction Necessity and Essence Naming and Reference Rules and Meaning Conclusion References.

Can we have a posteriori knowledge of modal facts? And if so, is that knowledge fundamentally a posteriori, or does a priori intuition provide the modal component of what is known? Though the latter view seems more straightforward, there are also reasons for taking the first option seriously.

Metaphors involve immense explanatory power and positive impact predominantly in the scientific education and popularization. Still the use of metaphors in science might be a double-edged sword. Introduction of the computer metaphor to many scientific fields in the last century resulted in reductionist approaches, oversimplifications and mechanistic explanations in science as well as in humanities. In this short commentary we developed further the computer metaphor by prof. Noble and the illusions this metaphor led to in genetics, linguistics and consequently DNA (...) linguistics. (shrink)

Gleichzeitig reformuliert er die Erbsundenlehre der christlichen Tradition, wenn er den Menschen als radikal bose bezeichnet. Heit zeigt, dass Kant die Spannung zwischen Freiheit und Sunde nur durch religiosen Vollzug fur uberwindbar halt.

What are the criteria for counting something as Buddhist? This discipline-defining question has become increasingly perplexing as Buddhism is transmitted across the globe, taking new forms as it adapts to new contexts, especially as non-Buddhists increasingly come to participate in the meditation activities of Buddhist communities in the West. Through an ethnographic analysis of a Shambhala center in the southern United States, this article suggests that the best way to talk about such groups is neither through categorizing membership demographics, nor (...) by ranking the different degrees of Buddhism practiced in Shambhala as more or less authentic, but rather by focusing on how the group ultimately coheres despite inevitable differences in opinion. Thus instead of defining what is ‘authentically’ Buddhist among Shambhalians, this article tracks the manner in which certain Buddhist forms of signification are shared regardless of personal religious identities, forging a community through common interest. (shrink)

The gradual crowding out of singleton and small team science by large team endeavors is challenging key features of research culture. It is therefore important for the future of scientific practice to reflect upon the individual scientist’s ethical responsibilities within teams. To facilitate this reflection we show labor force trends in the US revealing a skewed growth in academic ranks and increased levels of competition for promotion within the system; we analyze teaming trends across disciplines and national borders demonstrating why (...) it is becoming difficult to distribute credit and to avoid conflicts of interest; and we use more than a century of Nobel prize data to show how science is outgrowing its old institutions of singleton awards. Of particular concern within the large team environment is the weakening of the mentor–mentee relation, which undermines the cultivation of virtue ethics across scientific generations. These trends and emerging organizational complexities call for a universal set of behavioral norms that transcend team heterogeneity and hierarchy. To this end, our expository analysis provides a survey of ethical issues in team settings to inform science ethics education and science policy. (shrink)

For the last 30 years there have been debates in philosophy about the concept of rationality. In anglo-american circles they have been primary characterized as discussions about “justified beliefs.” By contrast, the debate in Germany among discourse-theorists (Habermas, Apel) has been linked to the problem of justification of communicative speech-acts (within the concept of the entire communicative situation). Herbert Schnädelbach has modified the discours-theoretical account. His concept can be regarded along a number of dimensions. He has developed a linguistic analysis (...) of the validity claims made in various speech-act situations (following Paul Taylor). In Schnädelbach’s view, normative characterizations of speech acts can be used descriptively, too. Furthermore, the hierarchy of justifications ends on the level of rational choice.My starting point here is: there is a fundamental distinction between justifications in everyday-life and a theoretical level of justification (discoursive justifications). Thus, I discuss the hierarchy of justifications developed by Schnädelbach.Furthermore, I evaluate Schnädelbach’s concept in a semantic perspective. I will show that Schnädelbach’s pragmatical account requires a semantic analysis. Without recourse to such analysis, we cannot understand the universe of normative language. (shrink)

In the Soviet scientific literature of 1920‒30 the concept of probability was holly debated. The frequency concept which was proposed by R. von Mises became popular among Soviet physicists belonging to the L.I. Mandelstam community. Landau and Lifshitz were also close to this concept in their famous course of theoretical physics. A.Khinchin, a mathematician who cooperated with Kolmogorov, opposed to the frequency conception. In this paper we try to demonstrate that the frequency position was connected with the anthropomorphous approach to (...) physics, whereas Khinchin’s positions implied the criticism of anthropomorphism and put forward the ideal of objective knowledge. (shrink)

The purpose of the research is to analyze the context, the essence, and the philosophical implications of Franz Rosenzweig's reconsideration of the ban on idolatry as an implication of pure monotheism. As often as not idolatry is defined generally as the adoration of some images that, representing deity, are considered to be autonomous and hereupon become the objects of worship. The study confines itself to the analysis of the significance of the ban on idolatry in Rosenzweig's interpretation of the concept (...) of difference that underlies his theoretical model of the Other. The consideration proceeds on the general assumption that the encounter of tradition with modernity is the factor that determines the radical change in the philosophies of societies under modernization. In this context, the ancient ban on idolatry means the rejection and prohibition of whatever representation as intricate mediation that is, in turn, the hallmark of modernity. However, according to Rosenzweig, idolatry is not the usage of images as the representations of the reputedly unrepresentable God, but the fixation on one image which would mean the arbitrary limitation of God's infinite freedom to reveal himself visually. This implies that the reconsidered ban on idolatry does not require the absolute prohibition of representation, but the latter should be construed as temporal. Such an approach prevents the identification of the representation of entity with this entity itself, the sign with the thing, and therefore prohibits self-referentiality. Rosenzweig's stance determines also his understanding of familiarity, unfamiliarity, and difference in art and translation. Rosenzweig's emphasis on the shocking influence of the defamiliarizing difference as the feature of the work of art correlates with his interpretation of the translation that should make stable shared senses unfamiliar. Thus, the reconsidered ban on idolatry underlies Rosenzweig's conception of the reconciliation between Jewish tradition and modernity. (shrink)

Some people are opposed to abortion in general because they loved their children when these were fetuses. While this may be a psychological explanation of why these people believe thus, and perhaps an argument for these people not to abort the children they love, it does not at first sight seem to be an argument for the..

What is the nature of our reasons for loving something? Why does a particular person or activity stimulate our imagination and hopes more deeply than others do? Is the reason in the object of our affection or in ourselves? Much philosophical debate revolves around this dichotomy between objective and subjective reasons for loving. In this paper I will instead propose that our reasons are primarily relational, having to do with the concept of affinity. Affinity, defined as “fitness” between two parties, (...) allows us to analyze loving activity in terms of a practical inference concerned with a long-term engagement in activities and relationships that are worthwhile and suitable to oneself. This approach does justice to the considerations on both sides of the debate. (shrink)