The transcription factor NF‐κB (p65/p50) plays a central role in the coordination of cellular responses by activating the transcription of numerous target genes. The precise role of the dynamics of NF‐κB signalling in regulating gene expression is still an open question. Here, we show that besides external stimulation intracellular parameters can influence the dynamics of NF‐κB. By applying mathematical modelling and bifurcation analyses, we show that NF‐κB is capable of exhibiting different types of dynamics in response to the same stimulus. (...) We identified the total NF‐κB concentration and the IκBα transcription rate constant as two critical parameters that modulate the dynamics and the fold change of NF‐κB. Both parameters might vary as a result of cell‐to‐cell variability. The regulation of the IκBα transcription rate constant, e.g. by co‐factors, provides the possibility of regulating the NF‐κB dynamics by crosstalk. (shrink)

It is of fundamental importance to understand how the individual processes of gene expression, transcription, and translation, as well as mRNA and protein stability, act in concert to produce dynamic cellular proteomes. We use the concept of response times to illustrate the relation between degradation processes and responsiveness of the proteome to system changes and to provide supporting experimental evidence: proteins with short response times tend to be more strongly up‐regulated after 1 hour of TNFα stimulation than proteins with longer (...) response times. Furthermore, based on process‐dependent response times, we demonstrate that synthesis and degradation act in concert to enable rapid responses. Finally, by building on a previously published data set quantifying the mammalian gene expression cascade, we speculate on how combinations of stable and unstable mRNAs and proteins may be wired to transcriptional or translational regulation to support gene function. (shrink)

Dorothea B. Heitsch is Assistant Professor of French and German at Shippensburg University in Pennsylvania.

First published in 1918, this volume was partly based on lectures delivered by Dorothea Jane Stephen at and near Bangalore and was intended to illustrate the considerable influence exercised by the early literature of India on later Indian philosophy and culture. Examining themes of divinity and religion together with morality and human nature, the essays in this book combine to offer a fitting introduction to the importance and far-reaching effects of early Indian thought.

The present paper considers our ability to ‘shape our own mental lives’; more specifically, it considers the claim that subjects sometimes can and do engage in ‘mental self-regulation’, that is, that subjects sometimes can be, and are, actively involved with their own mental lives in a goal-directed way. This ability of mental self-regulation has been rather neglected by contemporary philosophers of mind, but I show why it deserves careful philosophical attention. In order to further our understanding of the nature of (...) the phenomenon of mental self-regulation and to locate it within the wider context of our everyday lives and the world we live in, I proceed to develop some conditions which need to be met in order for a subject to be able to engage in mental self-regulation. In developing those conditions we find that compared to the physical realm, our mental lives are a rather elusive domain in the face of attempts at intervention, and our ability to intervene in our own mental lives is rather fragile. We also find that our ability to regulate our own mental lives in many cases depends on our possession of mental skills and mental know-how. Both these observations in turn throw new light on our understanding of the nature of the human mind. (shrink)

The aim of this chapter is to show how what I call critical republicanism can be developed on the basis of Pettit’s neo-republicanism. On the one hand, I argue that with regard to all three of the most important elements of a republican theory of non-domination, its normative core, the conception of domination, and its institutional implications, Pettit’s neo-republicanism does contain a powerful critical potential, too easily dismissed by some of his critics. On the other hand, I show how this (...) critical potential can be strengthened by reconceptualizing each of the elements of his theory of domination from a perspective inspired by the Kantian line of republican thought and contemporary Frankfurt School-style critical theory. (shrink)

ABSTRACT While multiple crisis phenomena have sparked experimentation with alternative forms of production and consumption on the micro level, it is not clear if and how these alternative practices may become hegemonic and thus displace capitalism as the hegemonic order on the macro level, rather than merely fostering pockets of a solidarity economy within capitalism. This question is hard to research, because it relates to post-capitalist futures rather than actual events or phenomena in the past or present. In this article, (...) I propose a methodological framework for studying the transformative potential of counter-hegemonic initiatives. Building on debates on causality and prediction within Critical Realism, I introduce the concept of ‘ex-ante’ retroduction. Using this mode of reasoning helps to identify possible generative mechanisms for the viability and achievability of alternative futures which can then be empirically investigated. (shrink)

The present paper offers a philosophical discussion of phenomena which in the empirical literature have recently been subsumed under the concept of ‘mental time travel’. More precisely, the paper considers differences and similarities between two cases of ‘mental time travel’, recollective memories (‘R-memories’) of past events on the one hand, and sensory imaginations (‘S-imaginations’) of future events on the other. It develops and defends the claim that, because a subject who R-remembers a past event is experientially aware of a past (...) particular event, while a subject who S-imagines a future event could not possibly be experientially aware of a future particular event, R-memories of past events and S-imaginations of future events are ultimately mental occurrences of two different kinds. (shrink)

ABSTRACT:Partnerships between companies and NGOs have received considerable attention in CSR in the past years. However, the role of NGO legitimacy in such partnerships has thus far been neglected. We argue that NGOs assume a status as special stakeholders of corporations which act on behalf of the common good. This role requires a particular focus on their moral legitimacy. We introduce a conceptual framework for analysing the moral legitimacy of NGOs along three dimensions, building on the theory of deliberative democracy. (...) Against this background we outline three procedural characteristics which are essential for judging the legitimacy of NGOs as potential or actual partners of corporations. (shrink)

The following paper considers one important feature of our experiential or ‘recollective’ memories, namely their spatial perspectival characteristics. I begin by considering the ‘Past-Dependency-Claim’, which states that every recollective memory (or ‘R-memory’) has its spatial perspectival characteristics in virtue of the subject’s present awareness of the spatial perspectival characteristics of a relevant past perceptual experience. Although the Past-Dependency-Claim might for various reasons seem particularly attractive, I show that it is false. I then proceed to develop and defend the ‘Present-Dependency-Claim’, namely (...) the claim that the spatial perspectival characteristics of an R-memory depend on the spatial perspectival characteristics of perceptual experiences that the subject has at the time at which the R-memory occurs. Lastly, I discuss the phenomenon of so-called ‘observer-memories’, which presents a special challenge for any attempt to account for the spatial perspectival characteristics of R-memories. I argue that we have no good reason to deny that the relevant experiences should count as memories, and I show that we can account for the spatial perspectival characteristics of observer-memories with the help of the ‘Present-Dependency-Claim’. More generally, the paper shows that certain events that occur in a subject’s mental life (namely, a subject’s R-memories) are necessarily dependent on other events that occur in the relevant subject’s mental life (namely, on certain perceptual experiences). This more general conclusion in turn should be relevant for any attempt to develop an appropriate account of a subject’s mental life as a whole. (shrink)

Dorothea Olkowski's exploration of the philosophy of Gilles Deleuze clarifies the gifted French thinker's writings for specialists and nonspecialists alike. Deleuze, she says, accomplished the "ruin of representation," the complete overthrow of hierarchic, organic thought in philosophy, politics, aesthetics, and ethics, as well as in society at large. In Deleuze's philosophy of difference, she discovers the source of a new ontology of change, which in turn opens up the creation of new modes of life and thought, not only in (...) philosophy and feminism but wherever creation is at stake. The work of contemporary artist Mary Kelly has been central to Olkowski's thinking. In Kelly she finds an artist at work whose creative acts are in themselves the ruin of representation as a whole, and the text is illustrated with Kelly's art. This original and provocative account of Deleuze contributes significantly to a critical feminist politics and philosophy, as well as to an understanding of feminist art. (shrink)

Imagine you are walking through a park. Suddenly, a mugger points a gun at you, threatening to shoot you if you do not hand over your valuables. Is this an instance of domination? Many authors working within the neo-republican framework - including Philip Pettit himself - are inclined to say 'yes'. After all, the mugger case seems to be a paradigmatic example of what it means to be at someone's mercy. However, I argue that this conclusion is based on a (...) misleading, interactional account of domination that misconceives its structural character. Domination, I maintain, is a structurally constituted form of power. Whether the mugger in the park dominates you or not can only be established by analysing the wider power structures in which your interaction is embedded. (shrink)

In order to be a self-governing agent, a person must govern the process by means of which she acquires the intention to act as she does. But what does governing this process require? The standard compatibilist answers to this question all assume that autonomous actions differ from nonautonomous actions insofar as they are a more perfect expression of the agent’s agency. I challenge this conception of autonomous agents as super agents. The distinguishing feature of autonomous agents is, I argue, the (...) nonagential role they play in the formation of their intentions. I offer an account of the relevant role. (shrink)

To treat some human beings as less worthy of concern and respect than others is to lose sight of their humanity. But what does this moral blindness amount to? In exploring the value of humanity, the essays in this volume offer a wide range of competing, yet overlapping, answers to this question. Some essays examine influential views in the history of Western philosophy. In others, philosophers currently working in ethics develop and defend their own views. Some essays appeal to distinctively (...) human capacities. Others argue that our obligations to one another are ultimately grounded in self-interest or certain shared interests or our natural sociability. The philosophers featured here disagree about whether the value of human beings depends on the value of anything else. They disagree about how reason and rationality relate to this value, and even about whether we can reason our way to discovering it. This rich selection of proposals encourages us to rethink some of our own deepest assumptions about the moral significance of being human. (shrink)

The original essays in this book address Harry Frankfurt's influential writing on personal identity, love, value, moral responsibility, and the freedom and ...

Sokrates – Platon – Aristoteles: Ohne die Bedeutung späterer Philosophen schmälern zu wollen, kann man sagen, dass es keine Lehrer-Schüler-Konstellation gegeben hat, die von vergleichbarer Bedeutung nicht nur für die Philosophiegeschichte, sondern für die Geistes- und Wissenschaftsgeschichte des Abendlandes überhaupt gewesen ist. Zugleich stellt uns dieses Dreigestirn jedoch vor die eigenartige Schwierigkeit, dass das persönliche wie auch das intellektuelle Verhältnis dieser drei Männer zueinander weitgehend im Dunkeln liegt, und dies, obwohl es vielerlei Zeugnisse über Sokrates gibt, Platons Werke vollständig, die (...) des Aristoteles zu einem guten Teil erhalten sind. Ferner bestehen über Daten und Lebensumstände der drei ›Väter‹ der griechischen Philosophie keine Zweifel. Wenn über die intellektuellen Beziehungen zwischen ihnen so große Unsicherheit herrscht, so ist dies nicht auf mangelndes Interesse der Fachleute zurückzuführen. Das Verhältnis zwischen Sokrates und Platon wie auch das zwischen Platon und Aristoteles steht bis heute immer wieder im Zentrum der Forschung. (shrink)

Keine ausführliche Beschreibung für "Kierkegaards Begriff der Wiederholung" verfügbar.

Envy is sometimes suggested as an underlying motive in the assessment of different economic allocations. In the theoretical literature on fair division, following Foley [Foley, D. (1967), Yale Economic Essays, 7, 45–98], the term “envy” refers to an intrapersonal comparison of different consumption bundles. By contrast, in its everyday use “envy” involves interpersonal comparisons of well-being. We present, discuss results from free-form bargaining experiments on fair division problems in which inter-and intrapersonal criteria can be distinguished. We find that interpersonal comparisons (...) play the dominant role. The effect of the intrapersonal criterion of envy freeness is limited to situations in which other fairness criteria are not applicable. (shrink)

Band 1. Von Augustinus bis Nietzsche -- Band 2. Das 20. Jahrhundert.

Joseph Nechvatal 'La Beaute tragique: Olkowski, Deleuze, and the 'Ruin of Representation'' _Film-Philosophy_, Deleuze Special Issue vol. 5 no. 36, November 2001.

This text addresses the profound human questions of love and work. Beginning with a historical introduction, the author progresses through adaptive problems that humans face, and concludes by showing how evolutionary psychology encompasses all branches of psychology.

The present article aims to show that a subject can only fully grasp the concept of the past if she has some experiential, or recollective, memories of particular past events. More specifically, I argue that (1) in order for a subject to understand the concept of the past, it is necessary that the subject understand the concept of a particular past event in such a way that it might contribute to her understanding of the concept of the past. (2) But (...) then, in order for a subject to understand the concept of a particular past event in such a way that it might contribute to her understanding of the concept of the past, it is necessary that the subject have some recollective memories of particular past events. (C) Hence, a subject can only understand the concept of the past if she has some recollective memories of particular past events. I defend the premises of the present argument against various objections, indicate why we should accept both premises, and accordingly end by endorsing the argument's conclusion. (shrink)

This volume contains articles covering a broad spectrum of proof theory, with an emphasis on its mathematical aspects. The articles should not only be interesting to specialists of proof theory, but should also be accessible to a diverse audience, including logicians, mathematicians, computer scientists and philosophers. Many of the central topics of proof theory have been included in a self-contained expository of articles, covered in great detail and depth. The chapters are arranged so that the two introductory articles come first; (...) these are then followed by articles from core classical areas of proof theory; the handbook concludes with articles that deal with topics closely related to computer science. (shrink)

Abstract: The article aims to sharpen the neo-republican contribution to international political thought by challenging Pettit’s view that only representative states may raise a valid claim to non-domination in their external relations. The argument proceeds in two steps: First I show that, conceptually speaking, the domination of states, whether representative or not, implies dominating the collective people at least in its fundamental, constitutive power. Secondly, the domination of states – and thus of their peoples – cannot be justified normatively in (...) the name of promoting individual non-domination because such a compensatory rationale misconceives the notion of domination in terms of a discrete exercise of power instead of as an ongoing power relation. This speaks in favour of a more inclusive law of peoples than Pettit (just as his liberal counterpart Rawls) envisages: In order to accommodate the claim of collective peoples to non-domination it has to recognize every state as a member of the international order. (shrink)