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)

We study the lattice of extensions of four-valued Belnap–Dunn logic, called super-Belnap logics by analogy with superintuitionistic logics. We describe the global structure of this lattice by splitting it into several subintervals, and prove some new completeness theorems for super-Belnap logics. The crucial technical tool for this purpose will be the so-called antiaxiomatic (or explosive) part operator. The antiaxiomatic (or explosive) extensions of Belnap–Dunn logic turn out to be of particular interest owing to their connection to graph theory: the lattice (...) of finitary antiaxiomatic extensions of Belnap–Dunn logic is isomorphic to the lattice of upsets in the homomorphism order on finite graphs (with loops allowed). In particular, there is a continuum of finitary super-Belnap logics. Moreover, a non-finitary super-Belnap logic can be constructed with the help of this isomorphism. As algebraic corollaries we obtain the existence of a continuum of antivarieties of De Morgan algebras and the existence of a prevariety of De Morgan algebras which is not a quasivariety. (shrink)

A compelling account of evil in which Adam Morton draws on fascinating examples as diverse as Augustine and Buffy the Vampire Slayer. Exciting and thought-provoking, On Evil is essential reading for anyone interested in a topic that attracts and.

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)

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)

According to some, such as Carruthers (2009, 2010, 2011, 2015), the confabulation data (experimental data showing subjects making false psychological self-ascriptions) undermine the view that we can know our propositional attitudes by introspection. He believes that these data favour his interpretive sensory-access (ISA) theory—the view that self-knowledge of our propositional attitudes always involves self-interpretation of our sensations, behaviour, or situational cues. This paper will review some of the confabulation data and conclude that the presence and pattern of these data do (...) not substantiate the claim that we cannot introspect our propositional attitudes. As a consequence of this discussion, I conclude that the ISA theory is not well supported by the empirical data. (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)

Behemoth is traditionally read as supporting Hobbes's science from the treatises, but it also goes beyond the strict limitations of Hobbes's science. Understanding how Hobbes expands his approach requires that we examine how A's confidence in institutional reform is met by B's cynicism. Hobbes shifts from an analysis of general inclinations to an analysis of the particular strategies that skilful sovereigns use to acquire and maintain peace. The result is a theory of the state that relies less on> institutional arrangement, (...) and more on effective statesmanship, than we typically see when considering Hobbes's treatises alone. (shrink)

language="EN"> The eighth annual meeting of the ASSC took place between June 25th and 28th in Antwerp, an extremely beautiful Belgian city, a major European port and the home of the Peter Paul Rubens, 'the prince of painters and painter of princes'. The meeting was held in a University building at the edge of the old town. This part of the city is remarkable both for the elegance of its architecture and for its innumerable short, interlocking, streets with oddly indistinguishable (...) names. The demands on spatial memory were high and some delegates may still be hunting for the conference dinner which took place, magnificently but improbably, in a hotel - the Elzenveld - inside a hospital. (shrink)

The slightest reflection shows that the conceptual material employed in writing history is that of the period in which a history is written. There is no material available for leading principles and hypotheses save that of the historic present. As culture changes, the conceptions that are dominant in a culture change. Of necessity new standpoints for viewing, appraising and ordering data arise. History is then rewritten.The problem referred to in this passage is well known both from the literature on the (...) subject and the practice of historiography: historical works get old, the development of science—particularly of historical science—determines a new approach to old problems, and, consequently, history is rewritten in a different way. The fact is incontestable. But how should it be interpreted? Why is it so? (shrink)

Sogdian Epigraphy of Central Asia and Semirech’e. By Vladimir A. Livshits, translated by Tom Stableford and edited by Nicholas Sims-Williams. Corpus Inscriptionum Iranicarum, pt. II: Inscriptions of the Seleucid and Parthian periods of Eastern Iran and Central Asia, vol. III: Sogdian IV. London: School of Oriental and African Studies, 2015. Pp. 315. £60.

The Collegium Phaenomenologicum has met in Umbria, Italy every summer since 1976; only COVID made it pause, and hopefully only temporarily. It has been a forum for deep and broad discussion of the phenomenological tradition; it has also been a place where that tradition has itself been broadened and deepened by generations of thinkers who came to study the classical texts and to do phenomenology. In 2019, over the course of three weeks in July, in three lecture courses, several talks (...) by visiting faculty, twelve text seminars sessions, art workshops, and very many informal talks over dinner, on the terrace, and on long walks through the town of Città di Castello and beyond, the Collegium worked on the question of critical phenomenology. (shrink)

Drones deployed to monitor endangered species often crash. These crashes teach us that using drones for conservation is a contingent practice ensnaring humans, technologies, and animals. This article advances a crash theory in which pilots, conservation drones, and endangered megafauna are relata, or related actants, that intra-act, cocreating each other and a mutually constituted phenomena. These phenomena are entangled, with either reciprocal dependencies or erosive entrapments. The crashing of conservation drones and endangered species requires an ethics of care, repair, or (...) reworlding. Diffractions, disruptions that expose difference, result from crashes and reveal the precarious manner by which technologies, laws, and discourses bring nature and culture together. To support crash theory, this article presents three ethnographic cases. A drone crash in the United Kingdom near white rhinoceroses while building machine learning training data exhibits the involvement of the electromagnetic spectrum; the threat of crashes in the Pacific Northwest near Puget Sound orcas discloses the impacts of drone laws; and drone crashes in Sri Lanka among Asian elephants presents the problems of technoliberal ideals around programming natural worlds. Throughout the article, a methodology is developed, parallelism, which attends to the material similarities in lateral phenomena. (shrink)

Originally published during the early part of the twentieth century, the Cambridge Manuals of Science and Literature were designed to provide concise introductions to a broad range of topics. They were written by experts for the general reader and combined a comprehensive approach to knowledge with an emphasis on accessibility. Plato: Moral and Political Ideals by Adela Marion Adam, first printed in 1913, deals with the main substance of Plato's philosophy of ethics and politics, set within the context of (...) his intellectual debt to Socrates. (shrink)

Reid's principle of credulity may be interpreted as equivalent to a principle of charity, due to the nature of three beliefs it implies concerning the interlocutors, which are held by the person who attempts to acquire their language: They are telling truth in the sense that they are saying what they really think, perceive, feel, believe; they are veracious in the sense that what they say is objectively true; they use language consistently. This interpretation relies on Reid's straightforward remarks on (...) his principle of credulity and on his view of two related correspondences: One correspondence is between the principle of credulity and the principle of veracity. The other is between these two principles and the principles that create the ‘language of nature’ and guide us in our efforts to unravel it. (shrink)

In this paper, a lesson is drawn from the way class definitions are provided in object-oriented programming. The distinction is introduced between the visible structure given in a class definition and the hidden structure, and then possible connections are indicated between these two structures and the structure of an entity modeled by the class definition.

According to a typical skeptical hypothesis, the evidence of your senses has been massively deceptive. Venerable skeptical hypotheses include the hypotheses that you have been deceived by a powerful evil demon, that you are now having an incredibly detailed dream, and that you are a brain in a vat. It is obviously reasonable for you now to be confident that neither of the above hypotheses is true. Epistemologists have proposed many stories to explain why that is reasonable. One theory is (...) that those hypotheses are inherently much less plausible than the hypothesis that your senses are basically reliable. Another theory is that you currently don’t believe any of those hypotheses, and that you need no justification to continue in that disbelief, given that your current beliefs cohere properly. A third theory is that —given that your senses are working properly—your sensory experiences themselves justify you in believing propositions such as the proposition that you have hands. Neo is given very good evidence that some skeptical hypothesis is true. He rightly becomes doubtful that his senses are or have been trustworthy. In fact, he becomes confident of a particular hypothesis: that AI’s created the Matrix, etc. But this is just one of many types of hypotheses that might account for his experiences. These types include. (shrink)