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)

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)

My strategy is to examine a recent trend in philosophical discussions of responsibility, a trend that tries, but I think ultimately fails, to give an acceptable analysis of the conditions of responsibility. It fails due to what at first appear to be deep and irresolvable metaphysical problems. It is here that I suggest that the condition of sanity comes to the rescue. What at first appears to be an impossible requirement for responsibility---the requirement that the responsible agent have created her- (...) or himself---turns out to be the vastly more mundane and non controversial requirement that the responsible agent must, in a fairly standard sense, be sane. (shrink)

At the very beginning of L’Homme-Machine, La Mettrie claims that Leibnizians with their monads have “rather spiritualized matter than materialized the soul”; a few years later Pierre-Louis Moreau de Maupertuis, President of the Berlin Academy of Sciences and natural philosopher with a strong interest in the modes of transmission of ‘genetic’ information, conceived of living minima which he termed molecules, “endowed with desire, memory and intelligence,” in his Système de la nature ou Essai sur les corps organisés. This text first (...) appeared in Latin in 1751 under the title Dissertatio inauguralis metaphysica de universali naturae systemate, with the pseudonym Dr Baumann; it was translated by Maupertuis in 1754 as Essai sur la formation des corps organisés and was later included in his 1756 Œuvres under the title Système de la nature. Now, it is clear that Maupertuis was a kind of Leibnizian; and that his molecule possessed higher-level, ‘mental’ properties. In that sense he falls under the first category described by La Mettrie. But he was also involved in a debate on this issue with Diderot, who put forth a sustained critique of Maupertuis’ theory of the molecule in the additions to his 1753 Pensées sur l’interprétation de la nature. Where Maupertuis attributes higher-level properties to his living minima, Diderot argues that these properties are ‘organizational’, i.e., they can only be properties of the whole. At issue here is the degree of commitment to a form of materialism. (shrink)

Bioethics has paid surprisingly little attention to the special problems faced by women and to feminist analyses of current health care issues other than ...

In the Transcendental Aesthetic (TA), Kant is typically held to make negative assertations about “things in themselves,” namely that they are not spatial or temporal. These negative assertions stand behind the “neglected alternative” problem for Kant’s transcendental idealism. According to this problem, Kant may be entitled to assert that spatio-temporality is a subjective element of our cognition, but he cannot rule out that it may also be a feature of the objective world. In this paper, I show in a new (...) way how Kant’s view (focusing on his conclusions about space) is not subject to this objection, by showing that he does not make the denial about mind-independent reality that he is typically held to make. The argument develops consequences of a new reading of Kant’s expression “an sich selbst” (‘in itself’; ‘in themselves’). I argue that “an sich selbst” or “per se” has a special, judgment-level role, so that this expression does not form new noun-terms adjectivally. It follows that the conceptual unit of Kant’s “Conclusions” in the TA is simply “things” (Dinge), since “things in themselves” is not a nominal expression; Kant adopts the Wolffian ontological use of “thing” as the basic kind-term for any existent. The arguments that things per se are not in space are arguments that space cannot be a necessary property or relations of things as a kind. I show that this does not involve the positive claim about mind-independent reality that inspires the neglected alternative objection. (shrink)

Příspěvek se snaží ukázat, jaký dopad mělo poznávání přírody Nového světa na utváření specific- kých podob raně novověké vědecké kooperace a vědy obecně. Záměrem textu je prezentovat originální metody a formy vědění, které v souvislosti s kooperativním poznáváním Nového světa především ve Španělsku vznikaly a jež v soudobé Evropě neměly obdobu. Studie tak chce poukázat na význam, který mělo poznávání Nového světa Španěly v procesu tzv. vědecké revoluce, resp. proměny vědecké praxe i teoretických episte- mologických schémat.

In his Philosophical Inquiry concerning Human Liberty (1717), the English deist Anthony Collins proposed a complete determinist account of the human mind and action, partly inspired by his mentor Locke, but also by elements from Bayle, Leibniz and other Continental sources. It is a determinism which does not neglect the question of the specific status of the mind but rather seeks to provide a causal account of mental activity and volition in particular; it is a ‘volitional determinism’. Some decades later, (...) Diderot articulates a very similar determinism, which seeks to recognize the existence of “causes proper to man” (as he says in the Réfutation d’Helvétius). The difference with Collins is that now biological factors are being taken into account. Obviously both the ‘volitional’ and the ‘biological’ forms of determinism are noteworthy inasmuch as they change our picture of the nature of determinism itself, but my interest here is to compare these two determinist arguments, both of which are broadly Spinozist in nature – and as such belong to what Jonathan Israel called in his recent book “the radical Enlightenment,” i.e. a kind of underground Enlightenment constituted by Spinozism – and to see how Collins’ specifically psychological vision and Diderot’s specifically biological vision correspond to their two separate national contexts: determinism in France in the mid-1750s was a much more medico-biological affair than English determinism, which appears to be on a ‘path’ leading to Mill and associationist psychology. (shrink)

This analysis investigates whether solidarity is an appropriate concept for thinking about justifications for a just distribution of bioethical goods in the international arena. This will be explored by looking at the national origins of the idea of justifying solidarity in the form of the health care that welfare states offer. Following that, ‘life’ and ‘health’ will be placed within a philosophical context by focusing on the main arguments of John Rawls and Amartya Sen and the role of solidarity in (...) these two theories of justice will be analysed. It will be shown that these theories assume that solidarity is not a prerequisite for just international structures. Finally, the possibility will be discussed, that there is a degree of uncertainty surrounding justifications for fair distribution in the international context that can result when the concepts of solidarity and justice are handled imprecisely. (shrink)

Sport provides an arena for human flourishing. For some, this pursuit of a meaningful life through sport involves the use of non-human animals, not least of all through sport hunting. This paper will take seriously that sport – including sport hunting – can provide a meaningful arena for human flourishing. Additionally, it will accept for present purposes that animals are of less moral value than humans. This paper will show that, even accepting these premises, much use of animals for sport (...) – including sport hunting – is unacceptable. Nonetheless it will show that there can be acceptable ways of using animals as part of a human’s meaningful life pursuits through sport, albeit in a more limited fashion than many sportspersons currently accept. (shrink)

This chapter discusses the analysis of Joseph Raz on coercion, trust, and citizenship. The chapter starts with a number of brief comments on some of his observations regarding the doctrine of liberty and the preference for minimum government. The chapter also includes one of Raz's arguments that states that some people favour non-perfectionist forms of government out of a misunderstanding of the implications of perfectionism for liberty.

Bringing these two emergent areas of thought into direct conversation in Before the Law, Cary Wolfe fosters a new discussion about the status of nonhuman animals and the shared plight of humans and animals under biopolitics.

First published in 1991. Routledge is an imprint of Taylor & Francis, an informa company.

Part of the draw of athletics is its straightforwardness. There are nuances to competitions to make them more sporting contests, but at the end of a long jump competition whomever records the longest jump should win. Unfortunately, a recent rule-change at the highest level of the sport – the “Final 3” format – undermined this simplicity for the horizontal jumps and the throws for some of the 2020 and much of the 2021 seasons. While fortunately this rule was largely reverted (...) within days of the initial submission of this paper, it’s still valuable to critically evaluate why such a rule is problematic so as to better understand of the value of sporting competitions and give guidance on future rule changes, be they in athletics or other sports. To that end, we will be drawing from the literature on the purpose and value of competitions and coupling that with simulations based on data from actual top-tier long jump competitions to show that the Final 3 format makes for significantly worse competitions than the standard format. (shrink)

Critical accounts over the past years have focused on neoliberalism as a subject of knowledge; there has been a recently growing interest in neoliberalism as an object of knowledge. This article considers the theoretical, epistemological and political implications of the relationship between neoliberalism as an epistemic subject and neoliberalism as an epistemic object. It argues that the ‘gnossification’ of neoliberalism – framing it an epistemic project, and deriving implications for political engagement from this – avoids engaging with numerous ambiguous elements (...) of the production of knowledge. Drawing on Bourdieu’s concept of the ‘scholastic fallacy’ and Boltanski and Chiapello’s work in sociology of critique, the article lays out a framework for the study of the relationship between epistemic, moral, and political elements of critique of neoliberalism, including the conditions of its own production in contemporary academic contexts. (shrink)

Conversational artificial intelligence (CAI) presents many opportunities in the psychotherapeutic landscape—such as therapeutic support for people with mental health problems and without access to care. The adoption of CAI poses many risks that need in-depth ethical scrutiny. The objective of this paper is to complement current research on the ethics of AI for mental health by proposing a holistic, ethical, and epistemic analysis of CAI adoption. First, we focus on the question of whether CAI is rather a tool or an (...) agent. This question serves as a framework for the subsequent ethical analysis of CAI focusing on topics of (self-) knowledge, (self-)understanding, and relationships. Second, we propose further conceptual and ethical analysis regarding human-AI interaction and argue that CAI cannot be considered as an equal partner in a conversation as is the case with a human therapist. Instead, CAI’s role in a conversation should be restricted to specific functions. (shrink)

We develop and apply a multi-dimensional conception of explanatory depth towards a comparative analysis of inflationary and bouncing paradigms in primordial cosmology. Our analysis builds on earlier work due to Azhar and Loeb (2021) that establishes initial condition fine-tuning as a dimension of explanatory depth relevant to debates in contemporary cosmology. We propose dynamical fine-tuning and autonomy as two further dimensions of depth in the context of problems with instability and trans-Planckian modes that afflict bouncing and inflationary approaches respectively. In (...) the context of the latter issue, we argue that the recently formulated trans-Planckian censorship conjecture leads to a trade-off for inflationary models between dynamical fine-tuning and autonomy. We conclude with the suggestion that explanatory preference with regard to the different dimensions of depth is best understood in terms of differing attitudes towards heuristics for future model building. (shrink)

In this essay I advocate for the pedagogical value of public philosophy. In public essays, philosophers craft short arguments in clear prose that avoids disciplinary specific technical terms. Such texts are pedagogically valuable both because they teach students philosophical ideas and also because they offer students a template for philosophical argumentation upon which to model their own writing. Here I report on some of the pedagogical practices I have used for teaching public texts to advanced and introductory level undergraduates in (...) order to demonstrate how public philosophy serves as a valuable resource for the teaching of philosophy that can help students develop their capacity for engaged philosophical thinking and the effective communication of philosophical ideas. (shrink)

Ce livre étudie, à travers une série d'épisodes allant de la philosophie des Lumières à notre époque, le problème du matérialisme dans l'histoire de la philosophie et l’histoire des sciences. Comment comprendre les spécificités de l’histoire du matérialisme, des Lumières à nos jours, au sein de la grande histoire de la philosophie et de l’histoire des sciences ? Quelle est l’actualité de l’opposition classique entre le corps et l’esprit ? Qu’est-ce que le rire ou le rêve peuvent nous apprendre du (...) matérialisme ? En traversant l’histoire de ce concept jusqu’à l’émergence d’un « nouveau matérialisme » contemporain, l’ouvrage vise à revitaliser le matérialisme et sa lecture. -/- . (shrink)

This article introduces the concept of epistemic positioning to theorize the relationship between identity-based epistemic judgements and the reproduction of social inequalities, including those of gender and ethnicity/race, in the academia. Acts of epistemic positioning entail the evaluation of knowledge claims based on the speaker’s stated or inferred identity. These judgements serve to limit the scope of the knowledge claim, making it more likely speakers will be denied recognition or credit. The four types of epistemic positioning – bounding (reducing a (...) knowledge claim to elements of personal identity), domaining (reducing a knowledge claim to discipline or field associated with identity), non-attribution (using the claim without recognizing the author) and appropriation (presenting the claim as one’s own) – are mutually reinforcing. Given the growing importance of visibility and recognition in the context of increasing competition and insecurity in academic employment, these practices play a role in the ability of underrepresented groups to remain in the academic profession. (shrink)

This paper explores the problem of racial privilege in US American feminist thought. Drawing on Gayatri Spivak’s analysis of ethics, particularly her ideas of epistemic discontinuity and teleopoietic reading, I argue that a specific kind of ethical openness can help feminist social-political philosophy better negotiate the legacy of white privilege. Spivak’s work calls for a reconsideration and reworking of the subject who theorizes. Her analysis of ethics suggests that racially privileged feminists must be able to confront their own complicity in (...) order to engage in political critique less likely to recreate historical patterns of racial domination and exclusion. (shrink)

Study of Inference (anumāna) according to the Nyāyabhūṣaṇa, an autocommentary by Bhāsarvajña, 10th century, on his Nyāyasāra, aphorism on Nyaya philosophy.

Electroconvulsive therapy (ECT), an efficient psychiatric treatment method, is one of the most controversial and the most stigmatized therapeutic approaches in medicine. ECT uses transcranial electrical impulses to induce artificial epileptiform paroxysm. For the first time it was used in 1938 by Italian neuro-psychiatrists Ugo Cerletti and Lucio Bini in treatment of schizophrenia. Efficacy of the method was proven in clinical practice, clinical studies and meta-analyses. ECT is the most efficient in the treatment of mood disorders and in lesser extent (...) in some other disorders. Important advance in ECT was the introduction of anaesthesia and muscle relaxation. It reduced adverse effect incidence and severity. Currently, ECT is associated mostly with anaesthesia adverse effects. Other adverse reactions include muscle pain, headache, prolonged paroxysm, cardiopulmonary complications. The most discussed and the most disturbing adverse effect is memory impairment which is usually transient. Incidence and severity of adverse effects is comparable to other therapeutic modalities. Examining the available information it appears, that modern practice of ECT in Europe (European Union member states) and USA is, apart from a few exceptions, in accordance with principles of beneficence and to some extent with autonomy and nonmaleficence. In many countries, the principle of justice is not respected – either because of limited availability or restrictive laws. In the Czech Republic the problem is non-existence of codified treatment guidelines and insufficient training of medical specialists. Aside from this, position of ECT in the Czech Republic is similar to that in the rest of Europe and in USA. (shrink)

Dieses Buch fragt danach, wie Recht und Rechtsprechung, Staats- und Rechtstheorie sowie moderne Verhaltensökonomie die Rationalität und den Egoismus des Menschen begreifen und wie dies die Wahl staatlicher Steuerungsinstrumente beeinflusst. Das scheinbar neuartige Instrument Nudging wird mit Blick auf Umweltschutzinstrumente, die Regulierung des Tabakrauchens und der Organspende in den öffentlich-rechtlichen Handlungsformenkatalog eingeordnet, wobei verfassungsrechtliche Grenzen diskutiert werden. Zielgruppe sind die an der "Metaebene" des Rechts und der Verhaltenssteuerung interessierten Leserinnen und Leser. Der Inhalt Zeigt Möglichkeiten und verfassungsrechtliche Grenzen staatlicher Verhaltenssteuerung (...) auf Diskutiert das egoistisch-rationale Menschenbild aus Sicht der Staats- und Rechtstheorie Ordnet Nudging systematisch in die öffentlich-rechtliche Handlungsformenlehre ein Die AutorinJana Maruschke war zwischen März 2016 und Oktober 2021 wissenschaftliche Mitarbeiterin am Lehrstuhl für öffentliches Recht, Umwelt- und Technikrecht sowie Rechtstheorie von Prof. Dr. Andreas Fisahn an der Universität Bielefeld. In diesem Rahmen hat sie sich vor allem mit Fragen des Umwelt- und Staatsrechts befasst. Das Rechtsreferendariat am Landgericht Bielefeld hat sie mit dem 2. Staatsexamen im Juni 2023 erfolgreich abgeschlossen. (shrink)

Für Aristoteles ist das Kontinuum ein potentiell Unendliches. Dieser Unendlichkeitsbegriff, den er neben dem prozessualen und aktualen einführte, wurde im Laufe der Philosophiegeschichte nicht mehr berücksichtigt. So verwenden ihn u.a. weder Kant noch Weyl in ihren Kontinuumsbetrachtungen, obwohl ihr Kontinuumsverständnis ihn geradezu nahelegt. - In dieser Arbeit werden zum einen die ontologischen Kontinuumslehren des Aristoteles und späterer Philosophen und Mathematiker behandelt, zum anderen erfährt die von Aristoteles im 6. Buch der «Physik» vorgelegte strukturelle Kontinuumsuntersuchung eine eingehende Würdigung.

The past years have witnessed a growing awareness of the role of institutions of knowledge production in reproducing the global climate crisis, from research funded by fossil fuel companies to the role of mainstream economics in fuelling the idea of growth. This essay argues that rethinking knowledge production for post-carbon futures requires engaging with the co-determination of modes of knowing and modes of governing. The ways in which knowledge production is embedded in networks of global capitalism shapes how we (can) (...) think about the future. The essay argues for an attentivity to the material and infrastructural sides of knowledge production, which will enable us to re-think transition to post-carbon futures in ways that recognize the deep structural, spatial and social inequalities underpinning knowledge production. (shrink)

While the idea of philosophy as conceptual analysis has attracted many adherents and undergone a number of variations, in general it suffers from an authority problem with two dimensions. First, it is unclear why the analysis of a concept should have objective authority: why explicating what we mean should express how things are. Second, conceptual analysis seems to lack intersubjective authority: why philosophical analysis should apply to more than a parochial group of individuals. I argue that Hegel’s conception of social (...) ontology, focused on his concept of “ethical life” (Sittlichkeit), helps to explain how concepts (and their explication) have both objective and intersubjective authority in the social domain. Hegel claims that modern institutions are the product of self-conscious purposes, so that they are conceptually constituted. Concepts do not just represent these objects and so depend on a contingent relation to them. As many contemporary social ontologists agree, this means that our concepts of these institutions are uniquely epistemically “transparent.” They have objective authority. Concepts have intersubjective authority in the modern world as well, according to Hegel. However, I show that this feature of Hegel’s account does not rely on the solution to a philosophical problem. Rather, since the concepts of modern ethical life are “essentially contested,” their content depends on the practical and political agreement of modern subjects. This means that concepts can only have objective authority if some prior intersubjective agreement has been reached. The role of philosophy as conceptual analysis is thus importantly dependent on political developments. (shrink)

The notion of trust has been discussed among several scientific fields, but it still lacks the joint theory. The goal was to analyze the trust associations of 600 participants and clarify how people associate the word “trust”. Overall, 600 participants produced 1800 associations which were sequentially divided into five domains and 14 categories. The findings imply, that when it comes to trust people tend to associate it mainly with relationships and positive emotions. The fact that associations involved mainly positive emotional (...) states and significant others may show, that trust in itself is something emotional and obviously bound to people we have the strongest bonds with. (shrink)