Industrial drug design methodology has undergone remarkable changes in the recent history. Up to the 1970s, the screening of large numbers of randomly selected substances in biological test system was often a crucial step in the development of novel drugs. From the early 1980s, such ‘blind’ screening was increasingly rejected by many pharmaceutical researchers and gave way to ‘rational drug design’, a method that grounds the design of new drugs on a detailed mechanistic understanding of the drug action. Surprisingly, however, (...) the chance-based method of random screening returned to center stage of industrial drug development in the 1990s in the form of ‘high-throughput screening’ (HTS). I will argue in this paper that this to-and-fro in the prominence of random screening comes with fundamental changes in the epistemic significance of chance experiments in pharmaceutical development. While up to the 1970s, random screening used to be chosen as an empirical search strategy primarily because suffi- cient knowledge of the mechanistic basis of drug action was lacking, it has turned with high-throughput screening into an experimental method that employs chance variation and testing to illuminate this mechanistic basis. As a consequence, research into the underlying mechanisms of drug action and the development of new drugs have become closely integrated. The rise of HTS therefore not only shows how chance experiments have assumed a new epistemic role in drug development. It also allows for a detailed study of the much debated emergence of a new relationship between scientific understanding and the development of technological artifacts. (shrink)

This teaching resource introduces undergraduate students to Chapter 2 of John Stuart Mill's Utilitarianism. John Stuart Mill was an English philosopher and well-known proponent of utilitarianism. This chapter is Mill's attempt to answer 'What is good?' and the implications of our answer for determining which actions are morally right. Mill thinks that, ultimately, happiness is the only thing that is good, and right actions are those which maximise happiness. In providing his answer, he considers and replies to several objections, including (...) that this account is 'worthy of swine', and that it is impossible to always be certain which actions will produce the most happiness over the long-term. This piece introduces summarises the main arguments and guides readers through the chapter, outlining the key concepts and exploring the wider implications of Mill's version of utilitarianism. (shrink)

Epistemology and Relativism Epistemology is, roughly, the philosophical theory of knowledge, its nature and scope. What is the status of epistemological claims? Relativists regard the status of epistemological claims as, in some way, relative— that is to say, that the truths which epistemological claims aspire to are … Continue reading Epistemology and Relativism →.

Reason has very often been seen as the highest faculty of man and, therefore, a strong tendency to attempt to analyze man mainly in terms of the rational dimension exists. This tendency was strong in antiquity and was given renewed attention in the seventeenth century.

Que faire quand tout est perdu? Céder la place aux fantômes.

All football teams that compete within the F. A. Premier League possess an academy, whose objective is to produce more and better home-grown players that are capable of playing professionally. These young players spend a large amount of time with their coach, but little is known about player’s perception of the coach-athlete relationship within F.A. Premier League Academies. The objectives of this study were to examine whether perceptions of the coach-athlete relationship changed over six months and if the coach-athlete relationship (...) predicted self-reported goal achievement among F. A. Premier League academy players. This study included cross-sectional (n = 104) and longitudinal (n = 52) assessments, in which academy soccer players completed a measure of the coach-athlete relationship and goal achievement across either one or two time periods. The cross-sectional data were subjected to bivariate correlations, whereas the longitudinal data were analyzed using multiple regressions. Perceptions of the coach-athlete relationship remained stable over time. The coach-athlete relationship predicted the achievement of mastery goals six months later. Enhancing the quality of the coach-athlete relationship among elite adolescent athletes appears to be a suitable way of maximizing mastery achievement goals, particularly among developmental athletes who participate in team sports. (shrink)

This article seeks to reconsider the meaning of the phrase al-shayṭān al-rajīm. It surveys the controversy surrounding the meaning of rajīm in this context and argues two points: first, that by the time the phrase was employed in the Qurʾan its original meaning had been forgotten, and second, that the original meaning of the term was related to Satan’s role as a heavenly accuser.

Michel Foucault's genealogies, due to their reliance on Nietzschean accounts of the violent origins of human culture, present a problematic description of the emergence of patterns of resistance and domination. By creating a parallel fiction of emergence that replaces Nietzschean originary violence with Richard Dawkins's account of the centrality of cultural transmission in human survival we can release emergence from the unitary Foucauldian drama. It is then possible to reconstruct Foucault's genealogies, anchoring the will to knowledge in an active agent (...) dedicated to the transgression of sociocultural limits. (shrink)

In defending the fundamentality of the open systems view for quantum theory, Cuffaro and Hartmann (2024) articulate an account of frameworks in physics. They argue that the general quantum theory of open systems is a more fundamental framework than standard quantum theory. In this chapter, we articulate an account of frameworks using the examples of quantum field theory and statistical mechanics. We argue that what makes frameworks useful in physics is the combination of generality and abstractness of frameworks. In particular, (...) their abstractness makes them poor targets for metaphysical analysis; the more concrete levels of theories or models are the appropriate target for ontological fundamentality claims. (shrink)

Drug development regularly has to deal with complex circumstances on two levels: the local level of pharmacological intervention on specific target proteins, and the systems level of the effects of pharmacological intervention on the organism. Different development strategies in the recent history of early drug development can be understood as competing attempts at coming to grips with these multi-level complexities. Both rational drug design and high-throughput screening concentrate on the local level, while traditional empirical search strategies as well as recent (...) systems biology approaches focus on the systems level. The analysis of these strategies reveals serious obstacles to integrating the study of interventive and systems complexity in a systematic, methodical way. Due to some fairly general properties of biological networks and the available options for pharmaceutical intervention, drug development is captured in an obstinate methodological dilemma. It is argued that at least in typical cases, drug development therefore remains dependent on coincidence, serendipity or plain luck to bridge the gap between development methodology and actual therapeutic success. (shrink)

L'auteur propose une réflexion sur le parcours et la pensée de Frantz Fanon, grande figure de l'anticolonialisme et du tiers-mondisme. Articulé autour de grands thèmes tels que la défense des cultures nationales ou la conscientisation de la jeunesse africaine, l'auteur entend ainsi répondre aux phénomènes d'aliénation ou de communautarisme qui caractérisent, selon lui, nos sociétés.

Multiple epistemological programs make use of intuitive judgments pertaining to an individual’s ability to gain knowledge from exclusively probabilistic/statistical information. This paper argues that these judgments likely form without deference to such information, instead being a function of the degree to which having knowledge is representative of an agent. Thus, these judgments fit the pattern of formation via a representativeness heuristic, like that famously described by Kahneman and Tversky to explain similar probabilistic judgments. Given this broad insensitivity to probabilistic/statistical information, (...) it directly follows that these epistemic judgments are insensitive to a given agent’s epistemic status. From this, the paper concludes that, breaking with common epistemological practice, we cannot assume that such judgments are reliable. (shrink)

According to a common view, the activity of justifying is epistemologically irrelevant: being justified in believing as one does never requires the ability to justify one’s belief. This view runs into trouble regarding the epistemic basing relation, the relation between a person’s belief and the reasons for which the person holds it. The view must appeal to basing relations as part of its account of what it is for a person to be justified in believing as she does, but the (...) view prevents basing relations from doing the needed work. In place of the common view, I propose an account of basing relations which links them to the person’s commitments and hence to her justificatory activity. If this proposal is correct, then positive justificatory status, too, will be conceptually linked to the ability to succeed in the activity of justifying. (shrink)

Bacterial chemotaxis is often considered to be a textbook example of the rudimentary semiotic process. As such, it gives an excellent opportunity to better understand both semiosis and biology. Our study reviews this phenomenon in the light of up-to-date scientific knowledge to answer the most basic semiotic questions: what is the sign? What types of signs are there? What is the meaning understood on the molecular level, and by what means can it grow with time? As a case study, the (...) bacterial chemotaxis toward glucose in E. coli species is chosen, and the semiotic framework of Charles Sanders Peirce applied. The analyses provide us with the following results: the sign, in its ultimate nature, is a general process. Bacterial chemotaxis can be understood in terms of Peircean type, symbol, and argument. The meaning on the molecular level is entirely pragmatic and, in this case, reduced to a bacterial response to glucose. A sign can grow through sign generalization, the emergence of different sign categories, the integration of these categories in functional cycles, and the introduction of contextuality. The sign of bacterial chemotaxis extends from the cell signaling pathways up to the population level. The presented results advance our knowledge of sign processing in the context of semiotic evolution. (shrink)

In the twentieth century, economic modernization projects were often part of a broader programme of social engineering, which did not avoid – and in many cases assumed – the use of violence. The author analyses the relationship between definitions of modernity developed by the classic authors of modernization theory during the 1950s and 1960s, tries to look for their roots in Marx’s writings on colonialism, and shows the consequences of the radical version of such projects, using the example of the (...) Chinese modernization programme implemented by Mao. In conclusion, Leszczyński assumes that a clear relationship can be traced between socio-economic modernization programmes and political violence in the twentieth century. (shrink)