Fanconi anemia (FA) is generally classified as a DNA repair disorder, conferring a genetic predisposition to cancer and prominent bone marrow failure (BMF) in early childhood. Corroborative human and murine studies point to a fetal origin of hematopoietic stem cell (HSC) attrition under replicative stress. Along with intriguing recent insights into non‐canonical roles and domain‐specific functions of FA proteins, these studies have raised the possibility of a DNA repair‐independent BMF etiology. However, deeper mechanistic insight is critical as current curative options (...) of allogeneic stem cell transplantation and emerging gene therapy have limited eligibility, carry significant side effects, and involve complex procedures restricted to resource‐rich environments. To develop rational and broadly accessible therapies for FA patients, the field will need more faithful disease models that overcome the scarcity of patient samples, leverage technological advances, and adopt investigational clinical trial designs tailored for rare diseases. (shrink)

gl. 1. Ėkofilosofii︠a︡ kak zhiznesokhrani︠a︡i︠u︡shchiĭ kulʹturnyĭ proekt -- gl. 2. Obrazy kulʹtury mira v istoriko-personologicheskom izmerenii -- gl. 3. Borʹba za mir v sovremennom mire : opyt, kont︠s︡ept︠s︡ii, modeli resheniĭ.

Wittgenstein’s concepts shed light on the phenomenon of schizophrenia in at least three different ways: with a view to empathy, scientific explanation, or philosophical clarification. I consider two different “positive” wittgensteinian accounts―Campbell’s idea that delusions involve a mechanism of which different framework propositions are parts, Sass’ proposal that the schizophrenic patient can be described as a solipsist, and a Rhodes’ and Gipp’s account, where epistemic aspects of schizophrenia are explained as failures in the ordinary background of certainties. I argue that (...) none of them amounts to empathic-phenomenological understanding, but they provide examples of how philosophical concepts can contribute to scientific explanation, and to philosophical clarification respectively. (shrink)

ResumoO argumento do milagre afirma que o realismo científico é a melhor explicação para o sucesso da ciência:teorias científicas são bem-sucedidas porque são verdadeiras, e cientistas são bem-sucedidos em encontrarteorias verdadeiras porque se baseiam em normas metodológicas confiáveis. A tese da incomensurabilidademetodológica afirma que teorias científicas não são escolhidas através de um algoritmo neutro de normas epistêmicas. Isso revela uma lacuna na explicação realista: normas epistêmicas confiáveis não são suficientes para conduzir a escolhas de teorias verdadeiras, pois tais escolhas também (...) são determinadas por outros fatores além de normas epistêmicas. A introdução de fatores adicionais como subdeterminando a escolha de teorias engendrou argumentos relativistas e antirrealistas contra o realismo. A explicação realista pode ser reabilitada se postular que os cientistas possuem autoridade epistêmica para aprimorar as normas metodológicas da ciência, sendo aptos a tomar decisões autônomas em vez de regidas por regras.AbstractThe no miracles argument claims that scientific realism is the best explanation to science’s success: scientifictheories are empirically successful because they are truthlike, and scientists are successful in theory-choices because they rely on reliable methodological norms. The methodological incommensurability thesis claims that there is no neutral algorithm for theory-choice. It reveals a gap in the realist explanation: reliable epistemic norms are not sufficient to guarantee successful theory-choices, because theory- choices are also determined by other factors besides epistemic norms. The introduction of additional factors as underdetermining theory-choices motivates relativist and antirealist positions. But the realist explanation can be rehabilitated if it postulates that scientists have epistemic authority to develop methodological norms, being apt to take decisions which are autonomous rather than rule-driven. (shrink)

The theory of intentionality is the most important core of the theoretical inheritance of E. Husserl’s phenomenology. Starting from this awareness, Levinas carries out a deep research within the phenomenology in order to see whether «intentionality exhausts modalities in which the thought is meaningful». This paper will try to show how the French-Lituan philosopher, going over the genetic phenomenology research which comes to a precategorial issue, can point out the «pre-intentional», or better the «non-intentional», the original «passivity» of conscience which (...) is not the negation of subjectivity, but instead the possibility of «giving» of transcendency. This «would not be a missed immanency», but would have in sociality – responsibility of the neighbour – the own spiritual excellency, which is the perfection of God. (shrink)

Philosophers have debated for millennia about whether moral requirements are always rational to follow. The background for these debates is often what I shall call “the self-interest model.” The guiding assumption here is that the basic demand of reason, to each person, is that one must, above all, advance one's self-interest. Alternatively, debate may be framed by a related, but significantly different, assumption: the idea that the basic rational requirement is to develop and pursue a set of personal ends in (...) an informed, efficient, and coherent way, whether one's choice of ends is based on self-interested desires or not. For brevity I refer to this as “the coherence-and-efficiency model.” Advocates of both models tend to think that, while it is sufficiently clear in principle what the rational thing to do is, what remains in doubt is whether it is always rational to be moral. They typically assume that morality is concerned, entirely or primarily, with our relations to others, especially with obligations that appear to require some sacrifice or compromise with the pursuit of self-interest. (shrink)

Contract is the dominant model for political philosophy's understanding of government grounded on the consent of the governed. However, there are at least five disabilities attached to classical social contract theory: the grounding contract never actually occurred; its provisions are vague and contestable; the stringency of the obligation thereby established is dubious; trans-generational consent is questionable; interpretive methods for giving effect to the contract are ill-specified. By contrast, the biblical story of the covenant Israel embraces at Sinai is shown to (...) be more adequately attentive to each of these five desiderata. The essay then focuses on the U.S. Constitution, arguing that in many ways it is more reflective of covenantal legitimating themes than those of social contract. The result is a promisingly different mode of understanding government by the consent of the governed. (shrink)

In this paper I shall venture into an area with which I am not very familiar and in which I feel far from confident; namely into phenomenology. My main motive is not to get away from standard, boring, methodological questions like those of induction and demarcation; but the conviction that a phenomenological account of the empirical basis forms a necessary complement to Popper's falsificationism. According to the latter, a scientific theory is a synthetic and universal, hence unverifiable proposition. In fact, (...) in order to be technologically useful, a scientific hypothesis must refer to future states-of-affairs; it ought therefore to remain unverified. But in order to be empirical, a theory must bear some kind of relation to factual statements. According to Popper, such a relation can only be one of potential conflict. Thus a theory T will be termed scientific if and only if T is logically incompatible with a so-called basic statement b, where b is both empirically verifiable and empirically falsifiable. In other words: T is scientific if it entails ¬b; where b, hence also ¬b, is an empirically decidable proposition. (shrink)

s div class="title" a terTwo Notions of Being: Entity and Essence s /div a ter - Volume 62 - E. J. Lowe.

Imagine a society of fisherfolk, who, in the state of nature, fish on a lake of finite size. Fishing on the lake is characterized by decreasing returns to scale in labor, because the lake's finite size imply that each successive hour of fishing labor is less effective than the previous one, as the remaining fish become less dense in the lake. In the state of nature, the lake is commonly owned: each fishes as much as he pleases, and, we might (...) suppose, calculates his fishing plan by taking the labor of the others as given, as he sees it. Each knows that the distribution of fish will be proportional to labor expended among the fisherfolk: if I fish twice as long as you, I will end up with twice as much fish as you. This is not due to some kind of concern with equity among the fisherfolk; it is a technological fact, implied by the assumption that fishing labor is homogeneous, and all are equally likely to catch a fish in a unit of time. An equilibrium under common ownership can be thought of as a Nash equilibrium of the game where each computes his optimal fishing plan, given the labor of the others and knowing what the consequent distribution of fish would be. (shrink)

In this innovative study of the relationship between persons and their bodies, E. J. Lowe demonstrates the inadequacy of physicalism, even in its mildest, non-reductionist guises, as a basis for a scientifically and philosophically acceptable account of human beings as subjects of experience, thought and action. He defends a substantival theory of the self as an enduring and irreducible entity - a theory which is unashamedly committed to a distinctly non-Cartesian dualism of self and body. Taking up the physicalist challenge (...) to any robust form of psychophysical interactionism, he shows how an attribution of independent causal powers to the mental states of human subjects is perfectly consistent with a thoroughly naturalistic world view. He concludes his study by examining in detail the role which conscious mental states play in the human subject's exercise of its most central capacities for perception, action, thought and self-knowledge. (shrink)

Encore un livre sur saint Thomas, dira-t-on. Que pourrait ajouter celui-ci à tout ce qui existe déjà? Nous voudrions d'abord dans cet ouvrage répondre simplement mais en vérité, et en lisant les textes eux-mêmes de saint Thomas et d'Aristote, à certaines objections ou lieux communs entendus ou lus plus ou moins régulièrement, qui empêchent de commencer à vouloir connaître la pensée de frère Thomas. Il s'agit de mettre en évidence la grande richesse, pour l'intelligence et le coeur humains, de sa (...) pensée philosophique, de ses analyses, de ses manières de poser les questions et d'interroger le réel. Un préambule pour une introduction à la philosophie de Thomas, telle est essentiellement l'intention de ces quatre études et non pas une introduction à la philosophie thomasienne purement et simplement. Elles cherchent ainsi à définir l'esprit d'un apprentissage philosophique qui a aussi en lui tout ce qui convient pour aider à un apprentissage théologique et spirituel, mystique même. (shrink)

The path of those who would approach the study of Bentham's writings on Evidence has been considerably smoothed by the recent publication of William Twining's work on the evidence theories of Bentham and Wigmore. The material on evidence is now being tackled by the Bentham Project. It presents no easy task. The central core, The Rationale of Judicial Evidence, edited and published by John Stuart Mill in 1827, exists only in the printed version, the MSS from which Mill worked having (...) disappeared. But a substantial body of related material which survives has yet to be thoroughly investigated, though William Twining has made a gallant start. A new edition of the work hitherto known as ‘An Introductory View of the Rationale of Evidence’, first printed in full in the Bowring edition of the Works of Jeremy Bentham is in preparation. The first fruits of this endeavour is that the title of that work as it should appear in due course in the new Collected Works will be Introduction to the Rationale of Evidence: An Introductory View for the Use of Lawyers as well as Non-lawyers, the title in fact given to the work by Bentham. It is intended that what follows should similarly be of use to non-lawyers as well as lawyers. (shrink)

In 1954 H. L. A. Hart wrote that Austin's work has ‘never, since his death … been ignored’. If it never has been completely ignored, interest in it has periodically waxed and waned. The interest definitely waxed in the 1980s. More books were published about Austin in this period than in any other decade since his death in 1859. Although this literature contains discussions of some of the nineteenth-century responses to his work, they are not the focus of it. Certain (...) of the responses remain completely in the dark, while there is more light to shed on at least some of the others. In short, our knowledge of nineteenth-century interpretations of Austin's legal philosophy is very incomplete. (shrink)

There is an undercurrent to be detected in Anselm's record of the meditative experience that issued in the Ontological Argument and, although it points to a profound and perennial problem in the interpretation of religion, this undercurrent has been largely ignored. The Argument, as is well known, moves entirely within the medium of reflective meaning focused on the idea of God and, unlike the cosmological arguments of later theologians, it makes no appeal whatever to a principle of causality or to (...) the discovery of a sufficient reason for finite existence. Anselm seems to have had his own sense of what one may call the unadulterated rationalism of the Argument when, in his own words, he wondered, ‘if perhaps it might be possible to find one single argument that for its proof required no other save itself, and that by itself would suffice to prove that God really exists’. Here we are entirely within that inner chamber of the mind so dear to the Augustinian tradition, a mind from which one is to exclude all thought save that of God. The task of the one who reflects is to penetrate the inner meaning of this thought in order to discover what it implies beyond what is evident on the surface. With such an eminently rational or logical aim occupying the centre of attention, it is quite understandable that the presence of another, and quite opposed, concern should have been overlooked - Anselm's concern, namely, to transcend, as it were, the medium of thought itself, and enter into the presence of God. The reason that this concern introduces a tension in the search for a proof is that the realization of presence would seem to render proof superfluous, while the inference in an argument - especially one moving towards existence – inevitably suggests, in some sense and to some degree, the absence of what is sought for. (shrink)

Préface.--De la nécessité historique du judéo-alexandrinisme.--Le juéo-alexandrinisme avant Philon.--Vie de Philon le Juif.--Classement de ses traités. Premier aspect de son œuvre.--Exposition de la philosophie de Philon.--Examen de la philosophie de Philon.

G.E. Moore, more than either Bertrand Russell or Ludwig Wittgenstein, was chiefly responsible for the rise of the analytic method in twentieth-century philosophy. This selection of his writings shows Moore at his very best. The classic essays are crucial to major philosophical debates that still resonate today. Amongst those included are: * A Defense of Common Sense * Certainty * Sense-Data * External and Internal Relations * Hume's Theory Explained * Is Existence a Predicate? * Proof of an External World (...) In addition, this collection also contains the key early papers in which Moore signals his break with idealism, and three important previously unpublished papers from his later work which illustrate his relationship with Wittgenstein. (shrink)

Les auteurs de cet ouvrage ont cherché à approfondir les fondements de la rationalité en philosophie des sciences pour montrer ce qu'une pensée rationnelle peut apporter à la démarche scientifique, pour mieux analyser un raisonnement ou les résultats d'une expérience. Les deux grands épistémologues et philosophes des sciences, Gaston Bachelard et Alexandre Koyré, les ont beaucoup inspirés dans leurs travaux, notamment sur la question du déterminisme. La pensée logique héritée d'Aristote, réduite au modus ponens, ne suffit pas aujourd'hui pour comprendre (...) l'avancée séculaire et fulgurante des connaissances en sciences. Les auteurs présentent à cet effet une étude des différentes méthodes de raisonnements. L'histoire des mathématiques, du point de vue de son épistémologie, fait l'objet d'un chapitre riche en citations montrant l'évolution de la pensée logique, d'Euclide à la théorie des ensembles, outil nécessaire à la progression des connaissances scientifiques. La mise en oeuvre de mesures expérimentales tenant compte des erreurs de mesure, suppose l'exploitation d'outils mathématiques et statistiques, illustrés par des exemples. Par leur approche zététique et épistémologique des connaissances, les auteurs ont souhaité que la pensée rationnelle ne s'efface pas sous le déferlement médiatique de certaines dérives et perversions de l'esprit scientifique propres aux altersciences, comme le scientisme, le positivisme ou le relativisme. (shrink)

Toujours, les révolutions s'inversent en terreur, la libération fait naître la domination, le pouvoir abuse, ment, échoue... Pourquoi continue-t-on pourtant à croire que le gouvernement des hommes a pour but de transformer la société alors qu'il se réduit souvent à une gestion de la situation? C'est cette question qui résonne singulièrement en ces temps de changement de gouvernance que lance ici Etienne Tassin, se reposant sur une formule de Merleau-Ponty : "On veut oublier un problème que l'Europe soupçonne depuis les (...) Grecs : n'y a-t-il pas un maléfice de la vie à plusieurs?" Les Grecs seront donc nos guides pour éclairer notre démocratie contemporaine, Oreste pour appréhender la question de la justice, Oedipe celle du maléfice, Antigone la dissidence, Socrate l'utopie, Caton les révolutions, Gygès les oubliés du régime libéral, Achille le courage, Diogène la question des migrants... Ils nous aideront à affronter cette idée tragique : il n'y a pas de bonne solution, la politique n'est pas une affaire de réussite ou d'échec mais de risque, celui de vivre à plusieurs. Elle est la condition humaine. (shrink)

Thomas E. Hill, Jr., interprets and extends Kant's moral theory in a series of essays that highlight its relevance to contemporary ethics. He introduces the major themes of Kantian ethics and explores its practical application to questions about revolution, prison reform, and forcible interventions in other countries for humanitarian purposes.

Frant︠s︡uzʹka revoli︠u︡t︠s︡ii︠a︡: prokhodz︠h︡enni︠a︡ cherez smertʹ -- Romantyzm i khytristʹ dobra: Mefistofel i︠a︡k kulʹturnyĭ heroĭ -- Narodz︠h︡enni︠a︡ totalʹnosti: slabkistʹ indyvida, syla kolektyvnykh til -- Klas i︠a︡k hrupa obranykh: marksyzm -- Rasa i︠a︡k "use": rasyzm i zakhid -- Hotui︠u︡chysʹ do katastrof: palinhenesii︠a︡ i kinet︠s︡ʹ stolitti︠a︡ -- Fashyzm: triumf transheokratiï -- Nat︠s︡yzm: rasa i︠a︡ zakon -- Komunizm: vid emansypat︠s︡iï do rabstva -- Rosiĭsʹka ideolohii︠a︡: sumishi ta ekstremy -- Zamistʹ vysnovkiv: plynnistʹ ideolohiĭ i XXI stolitti︠a︡.

Ancient moral philosophers, especially Aristotle and his followers, typically shared the assumption that ethics is primarily concerned with how to achieve the final end for human beings, a life of “happiness” or “human flourishing.” This final end was not a subjective condition, such as contentment or the satisfaction of our preferences, but a life that could be objectively determined to be appropriate to our nature as human beings. Character traits were treated as moral virtues because they contributed well toward this (...) ideal life, either as means to it or as constitutive aspects of it. Traits that tended to prevent a “happy” life were considered vices, even if they contributed to a life that was pleasant and what a person most wanted. The idea of “happiness” was central, then, in philosophical efforts to specify what we ought to do, what sort of persons we should try to become, and what sort of life a wise person would hope for. (shrink)