SummaryMutations in human genes encoding transcription factors are often dominant because one active allele cannot ensure a normal phenotype (haploinsufficiency). In other instances, heterozygous mutations of two genes are required for a phenotype to appear (combined haploinsufficiency). Here, we explore with models (i) the basis of haploinsufficiency and combined haploinsufficiency owing to mutations in transcription activators, and (ii) how the effects of such mutations can be amplified or buffered by subsequent steps in a transcription cascade. We propose that the non‐linear (...) (sigmoidal) response of transcription to the concentration of activators can explain haploinsufficiency. We further show that the sigmoidal character of the output of a cascade increases with the number of steps involved, the settings of which will determine the buffering or enhancement of the effects of a decreased concentration of an upstream activator. This exploration provides insights into the bases of compensatory mutations and on interloci interactions underlying oligogenic inheritance patterns. (shrink)

In the metabolic control theory, the control coefficient is a key parameter in quantifying the sensitivity of the flux towards an infinitesimal variation of enzyme activity. This concept does not apply just as it is for variations of enzyme concentrations whenever there is spatial, energy or resources limitations in the cell. Due to constraint on total enzyme concentration, the variation of concentration of any given enzyme may affect the concentrations of other enzymes. To take into account these correlations between enzyme (...) concentrations, we propose the concept of "combined response coefficient". Its definition is similar to that of the control coefficient, but its mathematical expression is different. Its range of variation is from – + 1, the null value corresponding to optimum enzyme concentration, i.e. to concentrations that maximise the flux, and the negative values to concentrations beyond the optimum value. A summation property could be derived using a simple weighting of the combined response coefficients, the sum of the weighed coefficient being 0. (shrink)

In this multi-disciplinary volume, comprising the work of several established scholars from different countries, central concepts associated with the work of the Bakhtin Circle are interrogated in relation to intellectual history, language theory and an understanding of new media. The book will prove an important resource for those interested in the ideas of the Bakhtin Circle, but also for those attempting to develop a coherent theoretical approach to language in use and problems of meaning production in new media.

From the book: What is to be done with political ecology? Nothing. What is to be done? Political ecology!

This article stages a new encounter between rhetoric and the philosophy of Karl Marx. We argue that the configuration of two major tropes in Marx’s 1852 pamphlet The Eighteenth Brumaire of Louis Bonaparte renders explicit the operative but implicit logics of Marxian historical materialism. Our reading therefore makes available a novel and untimely dimension of Marx’s conceptual labor where we least expect to find it: in a text that has been largely, but not exclusively, understood as a history of counterrevolution (...) that was meant to intervene within its own context in particular ways. While we do not wish to lose sight of that context, our aim is to demonstrate that The Eighteenth Brumaire is suggestive of the.. (shrink)

We present a conjecture in Diophantine geometry concerning the construction of line bundles over smooth projective varieties over ${\overline {\mathbb {Q}}}$. This conjecture, closely related to the Grothendieck period conjecture for cycles of codimension $1$, is also motivated by classical algebraization results in analytic and formal geometry and in transcendence theory. Its formulation involves the consideration of $D$-group schemes attached to abelian schemes over algebraic curves over ${\overline {\mathbb {Q}}}$. We also derive the Grothendieck period conjecture for cycles of codimension (...) $1$ in abelian varieties over ${\overline {\mathbb {Q}}}$ from a classical transcendence theorem à la Schneider–Lang. (shrink)

L'article montre comment l'édit de Nantes (1598), qui avait été critiqué par les protestants français au moment où il fut promulgué, devint peu à peu pour eux le symbole de leur appartenance à la communauté nationale française et de la reconnaissance de leur spécificité religieuse. Mais c'est en définitive après sa révocation (1685) que cet édit prend, aux yeux des porte-parole huguenots, toute sa valeur. Réfléchissant d'un point de vue théologique, mais aussi historique, juridique et philosophique, ils y voient le (...) symbole de la liberté religieuse. Cependant, c'est en faisant le deuil de leur statut perdu depuis la révocation de l'édit de Nantes qu'ils parviennent à développer une pensée originale à propos des rapports entre l'État et l'individu. Ils doivent pour cela distinguer le sujet ou Je citoyen d'une part, et Je croyant d'autre part. Or cette distinction impose de renoncer à la nostalgie d'un corps protestant, reconnu comme tel, au sein du royaume de France. (shrink)

Fichte assigns ‘intellectual intuition’ a new meaning after Kant. But in 1799, his doctrine of intellectual intuition is publicly deemed indefensible by Kant and nihilistic by Jacobi. I propose to defend Fichte’s doctrine against these charges, leaving aside whether it captures what he calls the ‘spirit’ of transcendental idealism. I do so by articulating three problems that motivate Fichte’s redirection of intellectual intuition from being to acting: (1) the regress problem, which states that reflecting on empirical facts of consciousness leads (...) only to further facts and so cannot yield a first principle; (2) the rhapsody problem, which states that the categories form a haphazard set and so lack necessity unless they derive from a first principle; and (3) the nihilism problem, which states that a first principle cannot lie outside our cognition of it, lest it be the cause of our cognition and, being first, the cause of all our actions, reducing us to machines. Crucially, Fichte’s three motivating problems are in fact aspects of a single problem. Leaving any aspect unsolved spoils putative solutions to the other two. Consequently, Fichte requires a single unified solution to all three, which his doctrine of intellectual intuition provides. (shrink)

I argue against the interpretation of propositions as intentions and proof-objects as fulfillments proposed by Heyting and defended by Tieszen and van Atten. The idea is already a frequent target of criticisms regarding the incompatibility of Brouwer’s and Husserl’s positions, mainly by Rosado Haddock and Hill. I raise a stronger objection in this paper. My claim is that even if we grant that the incompatibility can be properly dealt with, as van Atten believes it can, two fundamental issues indicate that (...) the interpretation is unsustainable regardless: (1) it is hard to determine, without appealing to propositional intentions on pain of circularity, what intention a proof-object should be understood as a fulfillment of; (2) due to a difficult fulfillment dilemma, it is unclear, at best, what the object of an intention corresponding to a proposition is. (shrink)

One of the most debated questions in psychology and cognitive science is the nature and the functioning of the mental processes involved in deductive reasoning. However, all existing theories refer to a specific deductive domain, like syllogistic, propositional or relational reasoning.Our goal is to unify the main types of deductive reasoning into a single set of basic procedures. In particular, we bring together the microtheories developed from a mental models perspective in a single theory, for which we provide a formal (...) foundation. We validate the theory through a computational model (UNICORE) which allows fine‐grained predictions of subjects' performance in different reasoning domains.The performance of the model is tested against the performance of experimental subjects—as reported in the relevant literature—in the three areas of syllogistic, relational and propositional reasoning. The computational model proves to be a satisfactory artificial subject, reproducing both correct and erroneous performance of the human subjects. Moreover, we introduce a developmental trend in the program, in order to simulate the performance of subjects of different ages, ranging from children (3–6) to adolescents (8–12) to adults (>21). The simulation model performs similarly to the subjects of different ages.Our conclusion is that the validity of the mental model approach is confirmed for the deductive reasoning domain, and that it is possible to devise a unique mechanism able to deal with the specific subareas. The proposed computational model (UNICORE) represents such a unifying structure. (shrink)

The combination of increased availability of large amounts of fine-grained human behavioral data and advances in machine learning is presiding over a growing reliance on algorithms to address complex societal problems. Algorithmic decision-making processes might lead to more objective and thus potentially fairer decisions than those made by humans who may be influenced by greed, prejudice, fatigue, or hunger. However, algorithmic decision-making has been criticized for its potential to enhance discrimination, information and power asymmetry, and opacity. In this paper, we (...) provide an overview of available technical solutions to enhance fairness, accountability, and transparency in algorithmic decision-making. We also highlight the criticality and urgency to engage multi-disciplinary teams of researchers, practitioners, policy-makers, and citizens to co-develop, deploy, and evaluate in the real-world algorithmic decision-making processes designed to maximize fairness and transparency. In doing so, we describe the Open Algortihms project as a step towards realizing the vision of a world where data and algorithms are used as lenses and levers in support of democracy and development. (shrink)

General-elimination harmony articulates Gentzen’s idea that the elimination-rules are justified if they infer from an assertion no more than can already be inferred from the grounds for making it. Dummett described the rules as not only harmonious but stable if the E-rules allow one to infer no more and no less than the I-rules justify. Pfenning and Davies call the rules locally complete if the E-rules are strong enough to allow one to infer the original judgement. A method is given (...) of generating harmonious general-elimination rules from a collection of I-rules. We show that the general-elimination rules satisfy Pfenning and Davies’ test for local completeness, but question whether that is enough to show that they are stable. Alternative conditions for stability are considered, including equivalence between the introduction- and elimination-meanings of a connective, and recovery of the grounds for assertion, finally generalizing the notion of local completeness to capture Dummett’s notion of stability satisfactorily. We show that the general-elimination rules meet the last of these conditions, and so are indeed not only harmonious but also stable. (shrink)

_Badiou and Politics_ offers a much-anticipated interpretation of the work of the influential French philosopher Alain Badiou. Countering ideas of the philosopher as a dogmatic, absolutist, or even mystical thinker enthralled by the force of the event as a radical break, Bruno Bosteels reveals Badiou’s deep and ongoing investment in the dialectic. Bosteels draws on all of Badiou’s writings, from the philosopher’s student days in the 1960s to the present, as well as on Badiou’s exchanges with other thinkers, from (...) his avowed “masters” Louis Althusser and Jacques Lacan, to interlocutors including Gilles Deleuze, Slavoj Žižek, Daniel Bensaïd, Jacques Derrida, Ernesto Laclau, and Judith Butler. Bosteels tracks the philosopher’s political activities from the events of May 1968 through his embrace of Maoism and the work he has done since the 1980s, helping to mobilize France’s illegal immigrants or _sans-papiers_. Ultimately, Bosteels argues for understanding Badiou’s thought as a revival of dialectical materialism, and he illuminates the philosopher’s understanding of the task of theory: to define a conceptual space for thinking emancipatory politics in the present. (shrink)

German classicist's monumental study of the origins of European thought in Greek literature and philosophy. Brilliant, widely influential. Includes "Homer's View of Man," "The Olympian Gods," "The Rise of the Individual in the Early Greek Lyric," "Pindar's Hymn to Zeus," "Myth and Reality in Greek Tragedy," and "Aristophanes and Aesthetic Criticism.".

In a series of papers Ladyman and Presnell raise an interesting challenge of providing a pre-mathematical justification for homotopy type theory. In response, they propose what they claim to be an informal semantics for homotopy type theory where types and terms are regarded as mathematical concepts. The aim of this paper is to raise some issues which need to be resolved for the successful development of their types-as-concepts interpretation.

This paper argues that we should solve paradoxes for propositions (such as the Russell–Myhill paradox) in essentially the same way that we solve Russellian paradoxes for sets. That is, the standard, iterative approach to sets is extended to include properties, and then the resulting hierarchy of sets and properties is used to construct propositions. Propositions on this account are structured in the sense of mirroring the sentences that express them, and they would seem to serve the needs of philosophers of (...) language and metaphysicians who rely on such propositions. The resulting account has limitations, comparable to those faced by the iterative approach to sets, but it is argued to be in important ways preferable to others that have been proposed. (shrink)

In a series of papers, 137–158; 1994, Midwest Studies in Philosophy, 23, 61–74, 1999) Fine develops his hylomorphic theory of embodiments. In this article, we supply a formal semantics for this theory that is adequate to the principles laid down for it in. In Section 1, we lay out the theory of embodiments as Fine presents it. In Section 2, we argue on Cantorian grounds that the theory needs to be stabilized, and sketch some ways forward, discussing various choice points (...) in modeling the view. In Section 3, we develop a formal semantics for the theory of embodiments by constructing embodiments in stages and restricting the domain of the second-order quantifiers. In Section 4 we give a few illustrative examples to show how the models deliver Finean hylomorphic consequences. In Section 5, we prove that Fine’s principles are sound with respect to this semantics. In Section 6 we present some inexpressibility results concerning Fine’s various notions of parthood and show that in our formal semantics these notions are all expressible using a single mereological primitive. In Section 7, we prove several mereological results stemming from the model theory, showing that the mereology is surprisingly robust. In Section 8, we draw some philosophical lessons from the formal semantics, and in particular respond to Koslicki’s main objection to Fine’s theory. In the appendix we present proofs of the inexpressibility results of Section 6. (shrink)

In his article Banicki proposes a universal model for all forms of philosophical therapy. He is guided by works of Martha Nussbaum, who in turn makes recourse to Aristotle. As compared to Nussbaum’s approach, Banicki’s model is more medical and less based on ethical argument. He mentions Foucault’s vision to apply the same theoretical analysis for the ailments of the body and the soul and to use the same kind of approach in treating and curing them. In his interpretation of (...) philosophical therapy, there are, however, some controversial issues, to which we would like to call attention: -/- Is restoring health by a philosophical method of treatment – health understood as a person’s ability to reach his/her vital goals – a convincing explication of philosophical therapy in general? In order to answer this question, it may be useful to look at Plato. It is not only Platonism (and especially Neo-platonism since Plotinus) that questions the idea that therapy is necessarily connected with „vital goals“. Buddhist and Gnostic philosophies are questioning „the vital“ in general. The immense effort in the history of philosophy to liberate the mind from the body casts doubt on the project to explain philosophical therapy solely in analogy to medical therapy. -/- According to Banicki a therapeutic philosophy has to identify the diseases it attempts at curing. There are, however, reasons for associating the term therapy with suffering/risk rather than disease. If a therapy aims at reducing the fear of death, as for example many classical philosophical therapies do, then there is no disease to be cured. A model based on chances and risks also has the advantage that the Buddhist and Stoic reinterpretation of desires/emotions as “diseases” can be dropped in contemporary philosophical therapy. -/- Banicki mentions the comparison of therapies as one of the primary goals of modelling. Methods should be verified by a statistical correlation between method and therapeutic success and/or by a theory which justifies the method. Some forms of therapies, however, avoid theory-specific terms and concepts in favor of an unprejudiced interpretation of the patient’s statements. Others share the (Nietzschean) aspiration to explore and change measures of value. If the therapeutic process is seen as a unique phenomenon, then there can be no theory and no statistics with co-occurrences. -/- According to Banicki philosophical therapy has to describe techniques which qualify as genuinely philosophical. Techniques like maieutics and hermeneutics, however, are antique philosophical “inventions”, which were later adopted by psychotherapy. If meditation is accepted as a therapeutic tool – as it was in ancient times – then there is not only a methodical but also an emotional relation to religion. If finally, the Socratic search for a good life is seen as one of the characteristics of philosophical therapy, then delimitation even turns into a criterion for non-philosophical therapies. The search for a good life requires an interdisciplinary approach. -/- For the concretization of the formal structure, we suggest a typology of therapies, which is based on chances and risks. Such a typology has the advantage, that it can model conflicting (and even opposing) forms of therapies. The variety of therapeutic goals and methods is a consequence of the historical development towards conceptual freedom. (shrink)

Research teams have made considerable progress in treating absolute uterine factor infertility through uterus transplantation, though studies have differed on the choice of either deceased or living donors. While researchers continue to analyze the medical feasibility of both approaches, little attention has been paid to the ethics of using deceased versus living donors as well as the protections that must be in place for each. Both types of uterus donation also pose unique regulatory challenges, including how to allocate donated organs; (...) whether the donor / donor's family has any rights to the uterus and resulting child; how to manage contact between the donor / donor's family, recipient, and resulting child; and how to track outcomes moving forward. (shrink)

Throughout his career, Schelling assigns knowledge of the absolute first principle of philosophy to intellectual intuition. Schelling's doctrine of intellectual intuition raises two important questions for interpreters. First, given that his doctrine undergoes several changes before and after his identity philosophy, to what extent can he be said to “hold onto” the same “sense” of it by the 1830s, as he claims? Second, given that his doctrine of intellectual intuition restricts absolute idealism to what he calls a “science of reason”, (...) which he says cannot prove the absolute’s existence, what other doctrine does he require in order to prove this? I will answer these questions by tracing the shifts in Schelling’s doctrine of intellectual intuition from the 1790s to the 1830s and drawing out its evolving methodological role within his science of intelligibility. (shrink)

European thought begins with the Greeks. Scientific and philosophic thinking--the pursuit of truth and the grasping of unchanging principles of life--is a historical development, an achievement; and, as Bruno Snell writes in The Discovery of the Mind, nothing less than a revolution. The Greeks did not take mental resources already at their disposal and merely map out new subjects for discussion and investigation. In poetry, drama, and philosophy they in fact discovered the human mind. The stages in man's gradual (...) understanding of himself are revealed in the course of ancient literature from Homer to Virgil. A rational view of the nature of man slowly established itself in the creations of epic and lyric poetry, tragedy and literary criticism, pre-Socratic thought, and early Greek ethics all the way to the discovery of humanitas and the spiritual landscape of Virgil's Arcadia. The Discovery of the Mind is a landmark work in tracing this evolution of consciousness--one of the distinguishing characteristics of the history of man. (shrink)

Serious actualism is the prima facie plausible thesis that things couldn’t have been related while being nothing. The thesis plays an important role in a number of arguments in metaphysics, e.g., in Plantinga’s argument for the claim that propositions do not ontologically depend on the things that they are about and in Williamson’s argument for the claim that he, Williamson, is necessarily something. Salmon has put forward that which is, arguably, the most pressing challenge to serious actualists. Salmon’s objection is (...) based on a scenario intended to elicit the judgment that merely possible entities may nonetheless be actually referred to, and so may actually have properties. It is shown that predicativism, the thesis that names are true of their bearers, provides the resources for replying to Salmon’s objection. In addition, an argument for serious actualism based on Stephanou, 219–250 2007) is offered. Finally, it is shown that once serious actualism is conjoined with some minimal assumptions, it implies property necessitism, the thesis that necessarily all properties are necessarily something, as well as a strong comprehension principle for higher-order modal logic according to which for every condition there necessarily is the property of being a thing satisfying that condition. (shrink)

pt. I. En tout temps, l'art comme figure du bonheur -- pt. II. La réinitialisation artistique de la culture -- pt. III. La réinitialisation des perceptions bienheureuses du monde.