New concepts may prove necessary to profit from the avalanche of sequence data on the genome, transcriptome, proteome and interactome and to relate this information to cell physiology. Here, we focus on the concept of large activity-based structures, or hyperstructures, in which a variety of types of molecules are brought together to perform a function. We review the evidence for the existence of hyperstructures responsible for the initiation of DNA replication, the sequestration of newly replicated origins of replication, cell division (...) and for metabolism. The processes responsible for hyperstructure formation include changes in enzyme affinities due to metabolite-induction, lipid-protein affinities, elevated local concentrations of proteins and their binding sites on DNA and RNA, and transertion. Experimental techniques exist that can be used to study hyperstructures and we review some of the ones less familiar to biologists. Finally, we speculate on how a variety of in silico approaches involving cellular automata and multi-agent systems could be combined to develop new concepts in the form of an Integrated cell (I-cell) which would undergo selection for growth and survival in a world of artificial microbiology. (shrink)

This book offers a systematic account of Wittgenstein's unique ethical thought, both in his early and in his later writings.

Shaul Magid's Meir Kahane: The Public Life and Political Thought of an American Jewish Radical (2021) stresses the American character of Kahane's thought. This review analyzes this claim in two ways. First, it offers a transnational perspective on Kahane's philosophy. Second, it examines Magid's concept of neo‐Kahanism in light of Kahane's legacy in Israel.

This article argues that constitutional mixture should be regarded as an inherent, inevitable feature of constitutions, and to some degree all constitutions are mixed. Thus, “mixed constitutions” should not be regarded as a distinct category of constitutions. Instead of asking whether a constitution is mixed, it might therefore be more useful to ask in which characteristics and to what extent a constitution is mixed. To demonstrate this, the article provides a preliminary typology of constitutional mixture considering the form or system (...) of government; the nature or character of government; the religious or secular identity; the flexibility or rigidity of the constitution; and its model of judicial enforcement—judicial or parliamentary supremacy. Examining these constitutional features, allows to shed light on the three different dimensions of “constitutional mixture”: First, the various features of the constitutional order do not function in a binary yes-or-no manner but appear and move along a spectrum. Second, the various features of the constitution change with time. Third, the various features of the constitutional text may be in tension with the features of the society. (shrink)

Ten years after the enactment of the Biologics Price Competition and Innovation Act, competition in biologics markets remains scant and far from sufficient for lowering prices of biologics to the level of 80-90% price drops seen in generic drug markets. This reality is not a result of one or two cardinal reasons, but many. If lowering the price of biologics is the goal and competition is the means by which we seek to achieve that goal, then there does not seem (...) to be a quick fix to address all of the many impediments to competition that plague biologics markets. Yet, certain changes to how the Food and Drug Administration evaluates and approves biologics may go a long way toward the creation of meaningful competition in biologics markets. One such change would be making original biologics' manufacturing information available to follow-on manufacturers.As recognized by several commentators, access to biologics manufacturing information is key to increasing competition in biologics markets. Without access to such information, making follow-on biologics is difficult and expensive, if not outright impossible. This is expected to be especially true for the highly anticipated class of interchangeable biologics, none of which has been approved by the FDA to date. Yet, it has long been the position of the brand-name pharmaceutical industry that biologics manufacturing information is proprietary and, thus, may not be shared. Congress has subscribed to the Industry's position, prohibiting the FDA from disclosing regulatory filings submitted by developers of original biologics, including manufacturing information, to third parties. That prohibition not only undermines competition in biologics markets, but is also wasteful, potentially unethical, and poses unnecessary risks to the health and safety of patients.This article makes the case for FDA sharing of original biologics manufacturing information with follow-on biologics developers. It is informed by the similar legal and commercial circumstances in the area of pesticides and the regulatory regime established by Congress in the Federal Insecticide, Fungicide and Rodenticide Act, which is administered by the Environmental Protection Agency. The article reviews the FIFRA regime, including its upholding as constitutional by the United States Supreme Court, and then examines its applicability to the area of biologics. The article concludes with a proposal for a similar regime to be incorporated into the pathway for approval of follow-on biologics as a means of increasing competition in biologics markets. (shrink)

In a recent paper, Dylan Evans proposed that emotions could help solve what has been known as ‘the frame problem’. In the process, he first questioned the utility of using the frame problem as a framework. After tackling this issue, he provided an alternative terminology to the frame problem—termed ‘the search hypothesis of emotion’—in order to re-examine how emotions aid rational agents. His new terminology, however, opens itself to other critiques. While accepting the basic tenets of his analysis, I question (...) (i) whether a single search theory of emotion is adequate, and (ii) whether his theory would have been better termed ‘the search hypothesis of feeling’. Finally, I extend some of the ideas developed in Evans' paper. 1. Introduction 2. Emotion, reason and ends 3. The search hypothesis of emotion revisited 4. Conclusion. (shrink)

Magnetic resonance imaging (MRI) is an imaging technique with a rapidly expanding application range. This methodology, which relies on quantum physics and substance magnetic properties, is now being routinely used in the clinics and medical research. With the advent of measuring functional brain activity with MRI (functional MRI), this methodology has reached a larger section of the neuroscience community (e.g. psychologists, neurobiologists). In the past, the use of MRI as a biomarker or as an assay to probe tissue pathophysiological condition (...) was limited. However, with the new applications of MRI: molecular imaging, contrast‐enhanced imaging and diffusion imaging, MRI is turning into a powerful tool for in vivo characterization of tissue pathophysiology. This review focuses on the diffusion MRI. Although it only measures the averaged Brownian translational motion of water molecules, using different analysis schemes, one can extract a wide range of quantitative indices that represent tissue morphology and compartmentalization. Statistical and visualization routines help to relate these indices to biologically relevant measures such as cell density, water content and size distribution. The aim of this review is to shed light on the potential of this methodology to be used in biological research. To that end, this review is intended for the non‐MRI specialists who wish to pursue biological research with this methodology. We will overview the current applications of diffusion MRI and its relation to cellular biology of brain tissue. BioEssays 30:1235–1245, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Freedom and security are often portrayed as things that have to be traded off against one another, but this view does not capture the full complexity of the freedom-security relationship. Rather, there seem to be four different ways in which freedom and security connect to each other: freedom can come at the cost of security, security can come at the cost of freedom, freedom can work to the benefit of security, and security can work to the benefit of freedom. This (...) paper analyses each of these connections in turn. It shows that particular understandings of freedom can help us to see particular connections between freedom and security. The practical examples used to illustrate these connections are drawn from the context of the COVID-19 pandemic. It will be suggested that, in the face of challenges such as this one, taking into account all four connections between freedom and security can ultimately help decision-makers in upholding both. (shrink)

The central thesis of this essay is that basic income experiments are justified if their expected benefits in terms of justice exceed their expected costs in terms of justice. The benefits are a function of basic income’s effect on the level of justice attained in the context in which it is implemented, and the experiment’s impact on future policy-making. The costs comprise the sacrifices made as a result of the experiment’s interventional character, as well as the study’s opportunity costs. In (...) light of the proposed standard of justification for basic income experiments, the factors that play a role in it, and the way these interact with one another, this essay provides some practical recommendations for researchers hoping to conduct such an experiment. (shrink)

ABSTRACT A common conclusion of lab dishonesty studies is that subjects cheat to a very modest extent even when they cannot get caught. The modest level of cheating is attributed to subjects’ moral feelings which restrict their cheating to a level that enables them to retain their self-image as honest individuals. The present paper questions this claim, reporting the results of two experiments which uncover a discrepancy between self-portrayed honesty and actual dishonest behavior. The experiments reveal, first, that self-portrayed honesty (...) is stricter than practical honesty, suggesting that when facing an opportunity to benefit from dishonest behavior, subjects trade off some of their self-image as honest persons for dishonestly-generated payoffs. Secondly, dishonesty out of lab, in subjects’ self-chosen environment, is greater than in the lab, with a considerable fraction of subjects cheating to the maximum extent possible. We suggest that it is not a concern about their self-image that holds subjects back from cheating maximally, but rather a concern about their social image. The modest level of dishonesty observed in the lab presumably reflects caution subjects exercise in an unsafe setup. Given an environment where they feel safe to reap the fruits of dishonesty without compromising their image as honest persons in the eyes of others, the image they have of themselves hardly plays a role in curbing their unethical behavior. (shrink)

In this paper, I argue for a wider application of Archon Fung's (2007) idea of a "pragmatic equilibrium". Would implementation of the practical recommendations that follow from a certain theory really contribute to the realisation of the values on which the theory was built? If political philosophers asked this question more often, this would benefit both the quality and the relevance of their theories. [Dutch].

As the COVID-19 pandemic was unfolding, a surge in scams was registered across the globe. While COVID-19 poses higher health risks for older adults, it is unknown whether older adults are also facing higher financial risks as a result of COVID-19 scams. Here, we examined age differences in vulnerability to COVID-19 scams and individual difference measures that might help explain them. A lifespan sample of sixty-eight younger, 79 middle-aged, and 63 older adults recruited through Prolific completed questions and questionnaires online. (...) In a within-subjects design, each participant responded to five COVID-19 solicitations, psychological measures, and demographic questions. Age group comparisons revealed that older adults were marginally less likely to perceive COVID-19 solicitations as genuine than middle-aged adults were. In addition, older adults perceived significantly fewer benefits than both younger and middle-aged adults did and perceived marginally higher risks than younger adults did. Hence, older adults did not exhibit greater vulnerability to COVID-19 scams. Regardless of age, intentions to respond to COVID-19 solicitations were positively predicted by higher levels of educational attainment, being married, past fraud victimization, and higher levels of positive urgency. As expected, stronger genuineness and benefit perceptions positively predicted action intentions, whereas stronger risk perceptions negatively predicted action intentions As such, COVID-19 scam susceptibility appears to be the result of a impulse control issue that is not easily inhibited, not even by past experiences of scam victimization. (shrink)

L'article montre que, contrairement à ce qui est généralement admis, il existe de la variation dans le sens des mots même en corpus spécialisés. Mise en relation avec les sous-domaines dont lesquels sont repérés ces différents sens, cette variation peut être assimilée à une variation de point de vue.

Proposed solutions to sustainability often bring different economic sectors into conflict; when a sustainable solution for one sector is non-sustainable for another it creates what we call the dilemma of sustainability. A recent example took place in the Columbia Basin of the Pacific Northwest, involving competing notions of sustainability by fisheries and the energy industry. Taking up some ideas of Eger and Lyotard, we criticize the constructivist approach which treats large ecosystems as constructions and the process of resolving conflicts of (...) sustainability as one solely consisting of negotiations involving the trading off of interests. We propose instead to treat such conflict resolution via a Gadamerian-inspired hermeneutics that sees different economic sectors as having different interpretations of sustainability and that aims at common understanding. (shrink)

INTRODUCTION: LE LIEU SÉMIOTIQUE JULIA KRISTEVA Les stoïciens furent probablement les premiers à developper une théorie détaillée du SIGNE - du ...

La confrontation Kant/Wittgenstein qui se dessine ici n'a pas pour objectif principal de présenter les doctrines des deux auteurs. Il s'agit plutôt de marier ces pensées qui ne le désirent pas, de profiter de la confrontation pour faire avancer le débat. Quel débat? Contrairement à I'ordre historique, il tire son origine de Wittgenstein: comment faut-il comprendre les prorèmes que soulève Wittgenstein, les interdits qu'il pose? Certaines de ses affirmations ne peuvent tout simplement pas être des jugements analytiques, aurait dit Kant. (...) Nombre de ses «remarques grammaticales» ne sont évidemment pas des tautologies, et la question se pose au moins de savoir comment elles sont possibles comme jugements analytiques. (shrink)

Le but de ces quelques remarques sur le jugement est de faire apparaître cette notion sous différents éclairages , tout en assurant une certaine progression d’un point de vue à l’autre. Dans la première section, il sera question non seulement de la synthèse au sens kantien du jugement synthétique fondé sur l’intuition, mais également des trois synthèses predicative, véritative et apophantique distinguées par Heidegger et reprises par Lotz. La deuxième section, plus proche de la pensée de Wittgenstein, s’interroge sur le (...) jugement dans le cadre de la « grammaire philosophique ». Enfin, la troisième section examine l’idée d’un primat du jugement sur la base du primat de la raison théorique soutenu par Jacques Poulain. En apparence, cette thèse prend le contre-pied de celle de Kant dans la Critique de la raison pratique, sans qu’on puisse lui attribuer la volonté de fonder une nouvelle « philosophie théorique ».The aim of the following remarks on judgment is to present this notion from different points of view , with a certain progression from the first to the others point of view. In the first section, it will be question not only of synthesis in the kantian sense which bears upon intuition, but equally of the three syntheses distinguished by Heidegger and Lotz. The second section, more wittgensteinian in spirit, asks the question of judgment in the context of the " philosophical grammar ". Finally, the third section investigates Jacques Poulain’s idea of a primacy of judgment on the basis of the primacy of theoretical reason over practical reason. At first sight, this thesis of Poulain seems to go against Kant’s thesis in the Critic of practical Reason, but we don’t have to attribute to him the will to establish a new " theoretical philosophy ". (shrink)

Based on electrophysiological and anatomical studies, a prevalent conception is that the visual system recovers features of the world from retinal images to generate perceptions and guide behavior. This paradigm, however, is unable to explain why visual perceptions differ from physical measurements, or how behavior could routinely succeed on this basis. An alternative is that vision does not recover features of the world, but assigns perceptual qualities empirically by associating frequently occurring stimulus patterns with useful responses on the basis of (...) survival and reproductive success. The purpose of the present article is to briefly describe this strategy of vision and the evidence for it. (shrink)