The role of acetylcholinesterase (AChE) in neurotransmission is well known. But long before synapses are formed in vertebrates, AChE is expressed in young postmitotic neuroblasts that are about to extend the first long tracts. AChE histochemistry can thus be used to map primary steps of brain differentiation. Preceding an possibly inducing AChE in avian brains, the closely related butyrylcholinesterase (BChE) spatially fore-shadows AChE-positive cell areas and the course of their axons. In particular, before spinal motor axons grow, their corresponding rostral (...) sclerotomes and myotomes express BChE, and both their neuronal source and myotomal target cells express AChE. Since axon growth has been found inhibited by acetylcholine, it is postulated that both cholinetsreases can attract neurite growth cones by neutralizing the inhibitor. Thus, the early expression of both cholinesterases that is at least partially independent from classical cholinergic synaptogenesis, sheds new light on the developmental and medical significance of these enzymes. (shrink)

This paper introduces a new, expanded range of relevant cognitive psychological research on collaborative recall and social memory to the philosophical debate on extended and distributed cognition. We start by examining the case for extended cognition based on the complementarity of inner and outer resources, by which neural, bodily, social, and environmental resources with disparate but complementary properties are integrated into hybrid cognitive systems, transforming or augmenting the nature of remembering or decision-making. Adams and Aizawa, noting this distinctive complementarity argument, (...) say that they agree with it completely: but they describe it as “a non-revolutionary approach” which leaves “the cognitive psychology of memory as the study of processes that take place, essentially without exception, within nervous systems.” In response, we carve out, on distinct conceptual and empirical grounds, a rich middle ground between internalist forms of cognitivism and radical anti-cognitivism. Drawing both on extended cognition literature and on Sterelny’s account of the “scaffolded mind” (this issue), we develop a multidimensional framework for understanding varying relations between agents and external resources, both technological and social. On this basis we argue that, independent of any more “revolutionary” metaphysical claims about the partial constitution of cognitive processes by external resources, a thesis of scaffolded or distributed cognition can substantially influence or transform explanatory practice in cognitive science. Critics also cite various empirical results as evidence against the idea that remembering can extend beyond skull and skin. We respond with a more principled, representative survey of the scientific psychology of memory, focussing in particular on robust recent empirical traditions for the study of collaborative recall and transactive social memory. We describe our own empirical research on socially distributed remembering, aimed at identifying conditions for mnemonic emergence in collaborative groups. Philosophical debates about extended, embedded, and distributed cognition can thus make richer, mutually beneficial contact with independently motivated research programs in the cognitive psychology of memory. (shrink)

This book presents new research into key areas of the work of German philosopher and mathematician Gottfried Wilhelm Leibniz (1646-1716). Reflecting various aspects of Leibniz's thought, this book offers a collection of original research arranged into four separate themes: Science, Metaphysics, Epistemology, and Religion and Theology. With in-depth articles by experts such as Maria Rosa Antognazza, Nicholas Jolley, Agustín Echavarría, Richard Arthur and Paul Lodge, this book is an invaluable resource not only for readers just beginning to discover (...) Leibniz, but also for scholars long familiar with his philosophy and eager to gain new perspectives on his work. (shrink)

Medicine is often thought of as a science of the body, but it is also a science of data. In some contexts, it can even be asserted that data drive health. This article focuses on a key piece of data technology central to contemporary practices of medicine: the medical record. By situating the medical record in the perspective of its history, we inquire into how the kinds of data that are kept at sites of clinical encounter often depend on informational (...) requirements that originate well outside of the clinic, in particular in health insurance records systems. Although this dependency of today's electronic medical records on billing requirements is widely lamented by clinical providers, its history remains little studied. Following the archaeology of medicine developed by Michel Foucault in The Birth of the Clinic and expanding his methodology in light of more recent contributions to the field of media archaeology, this article excavates some of the underexplored technological conditions that help constitute today's electronic medical record. If in some contexts, it is true that data drive health, then an archaeology of medical records helps reveal how health insurance records often impact clinical care and, by extension, health and disease. (shrink)

In this paper we briefly examine and evaluate Quine’s physicalism. On the supposition, in accordance with Quine’s views, that there can be no change of any sort without a physical change, we argue that this point leaves plenty of room to understand and accept a limited autonomy of the special sciences and of other domains of disciplinary and common-sense inquiry and discourse. The argument depends on distinguishing specific, detailed programs of reduction from the general Quinean strategy of reduction by explication. (...) We argue that the details of the relations of particular sciences, disciplines and domains of discourse depend on empirical evidence and empirical-theoretical developments and that the generalized approach of reduction by explication is also subject to related empirical-theoretical constraints. So understood, physicalism lacks much of the controversial force and many of the implications sometimes associated with it. (shrink)

In Paul Moser’s view, philosophical arguments of natural theology are irrelevant as evidence for God’s existence. I argue that embracing Moser’s view would bring about the end to the project and practice of Christian apologetics as we know it. I draw out implications from Moser’s work on religious epistemology for the project of Christian apologetics. I sketch what Christian apologetics would look like if one were to embrace Moser’s call to eliminate arguments as evidence for God existence. The result (...) of embracing Moser-style apologetics is apologetics without argument. I argue that Moserian apologetics should be rejected. (shrink)

Although the word 'sustainability' is used broadly, scientific approaches to sustainability fall into one of two competing paradigms. Following the influential Brundtland report of 1987. some theorists identify sustainability with some form of resource availability, and develop indicators for sustainability that stress capital depletion. This approach has spawned debates about the intersubstitutivity of capitals, with many environmental theorists arguing that at some point, depletion of natural capital cannot be offset by increases in human or social capital. The alternative approach is (...) grounded in stock and flow systems systems modeling, and defines sustainability through indicators that determine whether the system structure is robust (e.g. resists perturbation), resilient (recovers after disruption) and adaptive (capable of change in response to external conditions). Both paradigms have applications in economics and ecology. (shrink)

Ang Noli Me Tangere at El Filibusterismo ay mga nobelang isinulat ni Dr. Jose P. Rizal na sumasalamin sa kalagayan ng mga Pilipino noong panahon ng mga Español. Ikinubli ni Rizal ang mga di-makatáong pagtrato ng mga Español sa mga itinuring na Indio sa pamamagitan ng mga pangyayari at mga karakter sa kaniyang dalawang akda. Mula sa Teorya ng Moral na Pag-unlad (Theory of Moral Development) ng isang Amerikanong Sikolohistang si Lawrence Kohlberg ay sinuri ng papel na ito ang 10 (...) tagpo na nagpapakita ng katungkulang moral sa dalawang nobela gámit ang Antas at Yugto ng Moral na Pag-unlad ni Kohlberg (Kohlberg’s Levels and Stages of Moral Development). Mula sa ginawang pagsusuri, napagtanto ng papel na ito na gumamit si Rizal ng estratehiya upang ipakita na ang aksiyong isinagawa ng ahente sa bawat tagpo ay taliwas sa kaniyang kabuoang moralidad, bagaman ang pamamaraang ito ay nagdulot sa mga mambabása ng Noli Me Tangere at El Filibusterismo ng iba’t ibang interpretasyon at pagkaunawa sa mga isinulat ng may-akda. Mapanghámon ang mga nobela ni Rizal na sumusubok sa tradisyonal na kaugalian at panuntunan ng Pilipinas maging sa pagkukunwari ng lipunang Pilipino. Malaki ang naging gampanin ng nabuong tema na sumisimbolo sa mga isyung panlipunang nais palutangin ni Rizal. Gayunpaman, dahil sa mataas na pangangatwirang moral na nakapaloob sa kaniyang mga gawa, nararapat na gamítin ito hindi lámang bílang materyal sa pagaaral ng Filipino at sa mga kaugnay na larang, kundi pati rin sa pag-aaral ng kritisismo sa politika at lipunan, maging sa pag-aaral ng etika at moralidad, partikular na sa konteksto ng Pilipinas. (shrink)

Examples of extended cognition typically involve the use of technologically low-grade bio-external resources (e.g., the use of pen and paper to solve long multiplication problems). The present paper describes a putative case of extended cognizing based around a technologically advanced mixed reality device, namely, the Microsoft HoloLens. The case is evaluated from the standpoint of a mechanistic perspective. In particular, it is suggested that a combination of organismic (e.g., the human individual) and extra-organismic (e.g., the HoloLens) resources form part of (...) a common mechanism that realizes a bona fide cognitive routine. In addition to demonstrating how the theoretical resources of neo-mechanical philosophy might be used to evaluate extended cognitive systems, the present paper illustrates one of the ways in which mixed reality devices, virtual objects (i.e., holograms), and online (Internet-accessible) computational routines might be incorporated into human cognitive processes. This, it is suggested, speaks to the recent interest in mixed/virtual reality technologies across a number of disciplines. It also introduces us to issues that cross-cut disparate fields of philosophical research, such as the philosophy of science and the philosophy of technology. (shrink)

.... The strategy I have defended involves drawing a distinction between those who can and cannot legitimately hold an agent responsible in circumstances when the agent is being covertly controlled (e.g. through implantation processes). What is intuitively unacceptable, I maintain, is that an agent should be held responsible or subject to reactive attitudes that come from another agent who is covertly controlling or manipulating him. This places some limits on who is entitled to take up the participant stance in relation (...) to agents who are rational self-controllers but nevertheless subject to covert control.26 In this way, what is compromised by conditions of covert control is not the responsibility of the agent as such. It is, rather, the participant stance of those other agents who covertly control him. Clearly it is possible to establish these specific limits on who can hold these agents responsible without denying that the agents themselves remain free and responsible. When we take this approach we will find that we are no longer faced with an unattractive choice between simply “biting the bullet” or having to “spit it out”. All we need to do is chew carefully, until there is nothing left that we find too hard to swallow. (shrink)

English translation of an article originally published in French in Liber Amicorum Pascal Engel, J. Dutant, G. Fassio & A. Meylan (eds.), University of Geneva, 2014, pp. 581-608. In what follows, I strive to present the elements of a philosophical doctrine, which can be defined as dialectical contextualism. I proceed first to define the elements of this doctrine: dualities and polar contraries, the principle of dialectical indifference and the one-sidedness bias. I emphasize then the special importance of this doctrine in (...) one specific field of meta-philosophy: the methodology for solving philosophical paradoxes. Finally, I describe several applications of this methodology on the following paradoxes: Hempel's paradox, the surprise examination paradox and the Doomsday Argument. (shrink)

In this unpublished Latin fragment (which dates from May 1702) G. W. Leibniz criticizes the Cartesian conception of body and force and develops his own notion of matter, extension and his theory of forces. He argues against Descartes and Cartesians that 1) the essence of corporal bodies cannot be reduced to extension alone but the latter arise from the primitive force itself, 2) consequently Cartesian quantity of motion falls short to account the motive force of a moving body since the (...) true nature of physical bodies which can only be understood through a careful analysis of dynamical forces. -/- Mayıs 1702’de kaleme aldığı ve ölümünden sonra yayımlanan bu Latince fragmanda G. W. Leibniz, Kartezyen felsefenin cisim ve kuvvet anlayışını eleştirir ve kendi madde, uzam ve kuvvetler teorisini geliştirir. Leibniz, Descartes ve Kartezyenlere karşı 1) cisimlerin özünün yalnızca uzama indirgenemeyeceğini, bunun ilksel kuvvetin kendisinden kaynaklandığını, 2) sonuç olarak da Kartezyen hareket miktarının hareket eden bir cismin kuvvetini açıklamakta yetersiz kaldığını, çünkü fiziksel cisimlerin gerçek doğasının ancak dinamik kuvvetlerin dikkatli bir analiziyle anlaşılabileceğini ileri sürer. (shrink)

In this paper, I look at Susan Stebbing’s articles and reviews that critically engage logical positivism. These appeared before the publication of A.J. Ayer’s Language, Truth and Logic and helped shape the early British reception of logical positivism. I highlight Stebbing’s adoption of G.E. Moore’s tripartite distinction between knowing a proposition, understanding it, and giving an analysis of it and, in light of this distinction, her focus on whether the principle of verifiability can ground a plausible account of communication. Stebbing (...) thinks not, and I reconstruct her reasons, as well as her own account of communication. In doing this, I relate her criticisms to her rejection of methodological solipsism and her dissatisfaction with the logical positivist treatment of statements about other minds and the past. I also argue that Stebbing’s work provides a bridge to later criticisms of logical positivism from ordinary language philosophers. Foregrounding Stebbing’s engagement with logical positivism, especially her focus on communication, paints a fuller picture of how the logical positivists came to be part of analytic philosophy despite having different concerns than many of the British philosophers engaging their work. (shrink)

We aim to compile some means for a rational reconstruction of a named part of the start-over of Baruch (Benedictus) de Spinoza's metaphysics in 'de deo' (which is 'pars prima' of the 'ethica, ordine geometrico demonstrata' ) in terms of 1st order model theory. In so far, as our approach will be judged successful, it may, besides providing some help in understanding Spinoza, also contribute to the discussion of some or other philosophical evergreen, e.g. 'ontological commitment'. For this text we (...) assume the reader familiar with 'de deo' as well as with some basic concepts and results of 1st order model theory. Before we start reconstruction, we will first revisit shortly the concept of 'attributum' (definitio IV) in it's setting in 'de deo' , next scan for formalizable aspects of 'in suo genere finita' ('de deo', definitio II), subsequently list the model theoretic constructs we will make use of. Then we begin reconstruction by stating "coordinative definitions" for the notions of 'attribute (of a substance)', 'modus (as conceived via an attribute)' and 'substance (as conceived via an attribute)', reasoning shortly for each of them. The "coordinative definitions", we will arrive at, must not be understood as literal translations of Spinoza's concepts - of course, there can't be such a thing as a literal translation - they are meant as formal analoga of these concepts, mapping some logical structure. But even with this caveat they may seem strange to the reader at this stage of discussion. Additional justification for them then should be found in our endeavour, to map some argumentation of Spinoza's proofs of some of his propositions from this starting point. -/- [ Version 1 of this paper originated from 2020-03-14. This is version 2 from 2021-09-12 with some readability amendments. ]. (shrink)

The market failures approach to business ethics has recently garnered substantial critical attention (see, e.g., Cohen and Peterson 2019; Moriarty 2020; Steinberg 2017; Hsieh 2017; von Kriegstein 2016; Smith 2018; Endorfer and Larue 2022; Singer 2018). Though precursors of this view can be found in the literature (e.g., McMahon 1981; Friedman 1970), it was Joseph Heath (2004, 2006, 2014, 2023) who developed the approach and gave it its name. The market failures approach (henceforth: MFA) is concerned with the ethical obligations (...) of managers of firms (Heath 2014, 69). Roughly, it holds that managers ought not to conduct their businesses in a way that exploits market failures. “Market failure” is a technical term, meaning any failure of the conditions of the first fundamental welfare theorem, sometimes called the “Pareto conditions” (see Arrow 1951). The theorem states that if the Pareto conditions hold, then the market equilibrium will use society’s scarce resources efficiently, meaning that no one could be made better-off without making anyone else worse off. Efficiency, according to Heath (2014, chapter 7), is the implicit morality of the market. We coordinate much of our shared activity using markets, Heath claims, because of their ability to produce efficient results. Markets are good forms of social organization, according to Heath, because they are the best way to promote our values given empirical facts about the frailties of human psychology and the informational constraints that we face. As such, managers ought not compromise the very conditions that justify a market economy by profiting from breakdowns in the market’s efficiency. Managers are permitted to maximize profits, so long as they do not violate the market’s norm of efficiency in so doing. This is because the fundamental justification for the profit motive is that it is necessary for the operation of the price system which is essential to the efficiency properties of markets. In this paper, I will argue that the MFA is more general than even Heath himself claims. The MFA describes the professional obligations of managers, but the view I develop, the generalized market failures approach, describes the obligations of all market participants. Since efficiency is the implicit morality of the market, it binds not just managers, but all market participants, including consumers, investors and workers. Market participants are permitted to maximize the benefit they gain from market interactions, as long as they do so in a way that does not take advantage of any market failures. Generalizing the MFA in this way has three benefits: first, we gain a unified understanding of the ethics of non-managerial market roles; second, we will develop an even better understanding of the duties of managers; finally, it gives us the resources to respond to some familiar objections to the MFA found in the literature. In the next section, I will further motivate the MFA and explain how this motivation can be easily generalized to other market roles. Importantly, one can avoid benefiting from a market failure in two distinct ways: by avoiding transactions that exploit market failures or by transacting in such markets and then remediating the harm done, by compensating those negatively affected by the market failure. This section concludes by discussing how the remediation duties are to be split between the transacting parties and how to identify the parties to whom compensation is owed. In section 3, I use the tools of the generalized MFA to develop a unified ethics of consumption, investment and labor, respectively. This is the basis of a grand abductive argument for the generalized MFA. The view is strongly supported by the fact that it provides attractive and unifying explanations of our obligations in domains as variegated as carbon offsetting, CEO compensation, the reparations white Americans owe to black Americans and occupational licensure. Section 4 briefly concludes. (shrink)

In the introduction I argue that the basic element (or primitive) for constructing the physical universe is "displacement from a prior level", and the basic structure is "a sequence of such displacements" (summarized as postulates 1 and 2). The displacements are then defined as one-dimensional objects with a direction (postulate 3). The relations between these displacements are stated in postulate 4. In section 2 we discuss basic consequences of the postulates, and in section 3 we use the postulates to derive (...) a (3+1)-dimensional structure, interpreted as ordinary space and time. We then derive further properties of space --- isotropy, homogeneity, and a rapid early expansion (i.e. inflation). Time, comporting with experience, is shown to be a one-dimensional stream --- with a direction. In section 4 we associate energy with the displacements, and find that the same factors that construct ordinary space (and make it isotropic and homogeneous) also smear the locations of entities/particles across that space --- thereby providing a mechanism/explanation for that iconic and enigmatic aspect of quantum mechanics. We also determine that there must be a continual, uniformly-distributed stream of (non-zero-point) energy coming into the system that constructs new space (i.e. dark energy). The streaming natures of both time and dark energy are shown to have the same basic cause: the processes that input dark energy into the system, and that construct time, are themselves independent of time --- and so they are continual processes. Further consequences follow from the model, including an explanation for why the presence of energy affects space and time, and why quantum vacuum energy is an exception to this rule (i.e. does not gravitate) --- thereby eliminating the cosmological constant problem. A key benefit of the model is that it liberates us from always having to think about the construction of the universe in terms of spatio-temporal relations and evolution (e.g. the big bang model), which is problematic because presumably (and as we will indeed see) space and time are products of the fundamental construction process, not things that govern it. (shrink)

with some reference to my graffiti and arrest at U of G.

G.E.M. Anscombe famously remarked that an adequate philosophy of psychology was needed before we could do ethics. Fifty years have passed, and we should now ask what significance our best theories of the psychology of agency have for moral philosophy. My focus is on non-moral conceptions of autonomy and self-governance that emphasize the limits of deliberation -- the way in which one's cares render certain options unthinkable, one's intentions and policies filter out what is inconsistent with them, and one's resolutions (...) function to block further reflection. I argue that we can expect this deliberative "silencing" to lead to moral failures that occur because the morally correct option was filtered out of the agent's deliberation. I think it follows from these conceptions of self-governance that we should be considered culpable for unwitting acts and omissions, even if they express no ill will, moral indifference, or blameworthy evaluative judgments. The question is whether this consequence is acceptable. Either way, the potential tradeoff between self-governance and moral attentiveness is a source of doubt about recent attempts to ground the normativity of rationality in our concern for self-governance. (shrink)

Der endliche Mensch hat Probleme bei W a h r n e h m u n g oder V o r s t e l l u n g eines „unendlichen“ Raumes: als gleichzeitig oder als nacheinander. Die Vorstellung eines solchen Raumes führt für Paul Sturm zu einem Widerspruch. Dabei will er nicht stehen bleiben. Die Vorstellung dieses Raumes möchte er durch das D e n k e n „erweitern und vervollständigen“. Darin sieht er die Lösung dieses Konfliktes. Er (...) möchte das Bewusstsein dafür schärfen, dass sich das „Unendliche“ nicht vorstellen, sondern nur denken lässt. In der richtigen Formulierung der Problemstellung sieht Sturm ihre Lösung. Er legt dar, dass eine falsche Methode in der Vergangenheit stets zu einem Widerspruch führte, der sich als Sophisma (irrtümliche Schlussfolgerung) erweist. (Zusammenfassung verfasst von Michael Sturm-Berger und Beate Sturm). (shrink)

Grice bu yazıda temel olarak sezdirim kavramını incelemektedir. Sezdirim bir karşılıklı konuşmada konuşucunun, söylediği şey ötesinde dinleyicisine aktardığı düşüncedir. Konuşma sezdirimleri söz konusu olduğunda dinleyici, bir çıkarım sonucunda sezdirimleri saptar. Grice'ın savı, bu çıkarımda nicelik, nitelik, bağıntı ve tarz olmak üzere dört grupta toplanabilen ilkelerin (maksimler) belirleyici rol oynadığıdır.

Molecular developmental biology has expanded our conceptions of gene actions, underpinning that embryonic development is not only governed by a set of specific genes, but as much by space–time conditions of its developing modules. Typically, formation of cellular spheres, their transformation into planar epithelia, followed by tube formations and laminations are modular steps leading to the development of nervous tissues. Thereby, actions of organising centres, morphogenetic movements, inductive events between epithelia, tissue polarity reversal, widening of epithelia, and all these occurring (...) orderly in space and time, are driving forces of emergent laminar neural tissues, e.g. the vertebrate retina. Analyses of self-organisational formation of retina-like 3D structures from dispersed cells under defined cell culture conditions demonstrate that not only particular genetic networks, but—at least as important—the applied culture conditions define phenotypes of emergent tissues. Such in vitro approaches allow assigning emerging tissue formation to ground-laying genetic networks separately from contributions by conditional constraints. (shrink)

La traduction latine du livre de Maïmonide Moreh Nevukhim | Guide des égarés, a été l'ouvrage juif le plus influent des derniers millénaires (Di Segni, 2019 ; Rubio, 2006 ; Wohlman, 1988, 1995 ; Kohler, 2017). Elle marqua le début de la scolastique, fille du judaïsme élevée par des penseurs juifs, selon l'historien Heinrich Graetz (Geschichte der Juden, L. 6, Leipzig 1861, p. xii). Imprimée par la première presse mécanique de Gutenberg, son influence en Occident s'étendit jusqu'au Vème concile du (...) Latran (1512-1517) « où les savants furent encouragés à lever les difficultés qui semblaient diviser l'ensemble de la théologie et de la philosophie — (Leibniz, Théodicée, 11 ) ». Pendant des siècles, le Guide a révolutionné le programme d'instruction scolaire en réintégrant dans le domaine de la foi les lois de la pensée (dont la quatrième est devenue le principe de la raison suffisante de Leibniz). Cette collection complète de notes qui expose les idées du Guide fournit tous les passages sélectionnés et réécrits par Leibniz. Cette première traduction complète bilingue annotée des manuscrits originaux en latin sert de porte d'entrée à la foi conforme à la Raison. -/- « L'excellent livre du Rabbin Moïse Maïmonide, le Guide des égarés, est plus philosophique que je ne l'avais imaginé et mérite une lecture attentive. L'auteur, distingué par son intelligence en philosophie, était versé dans les mathématiques, l'art médical, et aussi dans la connaissance de Saintes Écritures. » — G. W. LEIBNIZ, 1685, Anthologie de Leibniz du Guide de Maïmonide, Chapitre III. (shrink)

Appears to give the first model-theoretic account of both "must" and "ought" (without conflating them with one another). Some key pre-theoretic semantic and pragmatic phenomena that support a negative answer to the main title question are identified and a conclusion of some significance is drawn: a pervasive bipartisan presupposition of twentieth century ethical theory and deontic logic is false. Next, an intuitive model-theoretic framework for "must" and "ought" is hypothesized. It is then shown how this hypothesis helps to explain and (...) predict all the pre-theoretic phenomena previously observed. Next, I show that the framework hypothesized possesses additional expressive and explanatory power (e.g. derivatively predicting the existence of supererogatory and permissibly suboptimal alternatives), thus adding further confirmation that it is on the right track. (shrink)

Don Ihde has characterized his philosophy as "phenomenology + pragmatism." This article argues that Ihde's pragmatism can be understood as consistency with two philosophical commitments from the first generation of American pragmatists (e.g. Peirce, James, Dewey and Addams). First, Ihde's notion of embodiment relations for tools and techniques is consistent with the organism-environment relational epistemology of these thinkers. Second, his desire to dissociate himself from romantic and neo-idealist readings of the phenomenological tradition link him with their naturalism.

RÉSUMÉL'interprétation de la philosophie pratique de Donald Davidson proposée par Robert Myers représente correctement maints aspects fondamentaux de sa pensée. Myers soutient à juste titre que Davidson évite les incohérences entre la position internaliste, l'objectivité éthique et le modèle croyance-désir en modifiant des éléments centraux de ce modèle, et que l'alternative proposée par Davidson rend légitime l'extension des arguments de l'interprétation et de la triangulation dans la sphère pratique. Cependant, Myers s’égare à une bifurcation cruciale de la route interprétative. Davidson (...) suit G.E.M. Anscombe sur une voie différente, une voie qui considère les désirs individuels comme constitués en partie par des jugements évaluatifs. (shrink)

The Mach-Zehnder Interferometer (MZI) is chosen to illustrate the long-standing wave-particle duality problem. Why is which-way (welcher weg) information incompatible with wave interference? How do we explain Wheeler’s delayed choice experiment? Most crucially, how can the photon divide at the first beam splitter and yet terminate on either arm with its undiminished energy? The position advanced is that the photon has two identities, one supporting particle features and the other wave features. There is photon kinetic energy that never splits (on (...) half-silvered mirrors) or diffracts (in pinholes or slits). Then there are photon probability waves that do diffract and can reinforce or cancel. Photon kinetic energy is oscillatory; its cycles require/occupy time. E = mc2 suggests that kinetic energy is physically real as occurrence in time just as rest mass is physically real as existence in space; both are quantized and both occupy/require a dimension for their occurrence or existence. Photon kinetic energy (KE) thus resides in time, but is still present/available for interactions (events) in space; rest mass (e.g., your desk) resides in space but is still present/available for interactions (events) in time. While photon probability waves progress in space and diffract there, photon KE resides in time and never diffracts in space; at reception it always arrives whole and imitates particle impact without being a particle. Photon probability waves are real; they diffract in space. Acknowledging that the photon has two identities (residing energy and progressing probability), explains photon dual nature. And wave-particle duality is central to quantum mechanics. Understanding it leads to new insights into entanglement, nonlocality and the measurement problem. A 30-minute video on nonlocality and photon dualism can be found by a google: search “youtube klevgard nonlocality”). (shrink)

A história da psicologia, tal como aparece em algumas obras (E.G. Boring 1950; M. Reuchlin 1957; P. Fraisse e J. Piaget 1963) ou em capítulos introdutórios de alguns manuais (M. Reuchlin 1977), reflete uma adesão — raramente discutida — a uma concepção internalista. Segundo essa concepção, a psicologia seria animada por uma dinâmica própria, um processo evolutivo totalmente endógeno, e seria independente de fatores externos tais como os domínios religiosos, sociopolíticos e econômicos. Além do mais, os partidários dessa história aceitam (...) ver a psicologia influenciada por disciplinas situadas em suas fronteiras, como a biologia, a fisiologia e, em menor medida, a física. Esses domínios fronteiriços geralmente dizem respeito a objetos psicológicos habitualmente qualificados de inferiores, como reflexos, sensações e percepções, em oposição à linguagem e ao pensamento, qualificados como processos superiores. Esses mesmos domínios fronteiriços engendraram por sua vez subdomínios relativamente autônomos, tais como a psicofísica ou a psicofisiologia. Correlativamente a essa concepção internalista, o desenvolvimento científico é apresentado como um caminho ao estado de psicologia positiva, tal como A. Comte a definiu em 1837 na 45a lição do Curso de Filosofia Positiva. A caminhada até a positividade foi indicada pelo próprio A. Comte: estudo da anátomo-fisiologia do sistema nervoso (a frenologia de Gall lhe parece a esse respeito uma contribuição decisiva), estudos comparados, análise de casos patológicos, estudo dos comportamentos animais e do desenvolvimento individual. Considerando a evolução da psicologia nos últimos cem anos, seríamos tentados a sustentar que ela realizou o projeto positivista. Psicologia diferencial, psicopatologia, etologia animal e psicologia da criança são vários domínios que concorrem para essa realização. Entretanto, esses domínios estão longe de parecerem homogêneos quanto aos métodos empregados e os modelos epistemológicos aos quais se referem. Um exame atento dessas dimensões metodológicas e epistemológicas mostra que se avança, sobretudo, em ordem dispersa. (shrink)

Although our concepts of “Mama,” “milk,” and “mice” have much in common, the suggestion that they are identical in structure in the mind of the prelinguistic child is mistaken. Even infants think about objects as different from substances and appreciate the distinction between kinds (e.g., mice) and individuals (e.g., Mama). Such cognitive capacities exist in other animals as well, and have important adaptive consequences.

Four initial postulates are presented (with two more added later), which state that construction of the physical universe proceeds from a sequence of discrete steps or "projections" --- a process that yields a sequence of discrete levels (labeled 0, 1, 2, 3, 4). At or above level 2 the model yields a (3+1)-dimensional structure, which is interpreted as ordinary space and time. As a result, time does not exist below level 2 of the system, and thus the quantum of action, (...) h, which depends on time (since its unit is time•energy), also does not exist below level 2. This implies that the quantum of action is not fundamental, and thus e.g. that the physical universe cannot have originated from a quantum fluctuation. When the gravitational interaction for the model is developed, it is seen that the basic ingredient for gravity is already operating at level 1 of the system, which implies that gravity, too, is not fundamentally quantum mechanical (since, as stated, h only kicks in at level 2) --- perhaps obviating the need for a quantum theory of gravity. Further arguments along this line lead to the conclusion that quantum fluctuations cannot be a source of gravity, and thus cannot contribute to the cosmological constant --- thereby averting the cosmological constant problem. Along the way, the model also provides explanations for dark energy, the beginning and ending of inflation, quark confinement, and more. Although the model dethrones the quantum, it nevertheless elevates an idea in physics that was engendered by quantum mechanics: the necessary role of "observers" in constructing the world. (shrink)

My review of Boghossian's book, Fear of Knowledge, is generally sympathetic toward his rejection of epistemic relativism and turns toward an examination of "constructivist" themes in light of an anti-nominalist perspective. In general terms, this is a fine little book, tightly argued, and well worth considerable attention--especially from the friends of relativism and those supporting versions of constructivism. (Constructivism + radical nominalism = relativism.).

This paper proposes an interpretation of time that is an 'A-theory' in that it incorporates both McTaggart's A-series and his B-series. The A-series characteristics are supposed to be 'ontologically private' analogous to qualia in the problem of other minds and is given a definition. The main idea is that the experimenter and the cat do not share the same A-series characteristics, e.g the same 'now'. So there is no single time at which the cat gets ascribed different states. It is (...) proposed one may define a 'unit of becoming' that coordinatizes the future/present/past 'private' spectrum as well as allowing one to calculate the rates of becoming. Relativity is briefly considered. (shrink)

This paper proposes an interpretation of time that is an 'A-theory' in that it incorporates both McTaggart's A-series and his B-series. The A-series characteristics are supposed to be 'ontologically private' analogous to qualia in the problem of other minds, such as in the Inverted Spectrum thought experiment, and is given a definition. The main idea is then that the experimenter and the cat do not share the same A-series characteristics, e.g. the same 'now', to some extent. So there is no (...) single time at which the cat gets ascribed different states, one by the experimenter and one by the cat. Also it is proposed one may define an ontologically private 'unit of becoming' that coordinatizes the future/present/past A-series spectrum as well as allow one to calculate rates of becoming with seconds. The latter are taken to measure differences in B-series times. (shrink)

The article traces the evolution and crystallization of Buber’s philosophy of dialogue. It focuses on his consideration of the epistemological and ontological issues attendant to the principium individuationis, the subject of his doctoral dissertation of 1904. Culminating with the publication of Ich und Du in 1923, this process was punctuated by life experiences that led him to affirm rather than to seek to transcend the principium individuationis as the ontological ground of being manifest in the matrix of everyday life, which (...) we are beckoned to sanctify through I-Thou relations. (shrink)

Paul Silva has recently argued that doxastic justification does not have a basing requirement. An important part of his argument depends on the assumption that doxastic and moral permissibility have a parallel structure. I here reply to Silva's argument by challenging this assumption. I claim that moral permissibility is an agential notion, while doxastic permissibility is not. I then briefly explore the nature of these notions and briefly consider their implications for praise and blame.

This book’s goal is to give an intellectual context for the following manuscript. -/- Includes bibliographical references and an index. Pages 1-123. 1). Philosophy. 2). Metaphysics. 3). Philosophy, German. 4). Philosophy, German -- 18th century. 5). Philosophy, German and Greek Influences Metaphysics. I. Hegel, Georg Wilhelm Friedrich -- 1770-1831 -- Das älteste Systemprogramm des deutschen Idealismus. II. Rosenzweig, Franz, -- 1886-1929. III. Schelling, Friedrich Wilhelm Joseph von, -- 1775-1854. IV. Hölderlin, Friedrich, -- 1770-1843. V. Ferrer, Daniel Fidel, 1952-. (...) [Translation from German into English of the-- Das älteste Systemprogramm des deutschen Idealismus.]. -/- Note: the manuscript is in the handwriting of G.W.F. Hegel, but the actual authorship is disputed. No date is given. Franz Rosenzweig made up the title as it is known today. He published the text in 1917. At that time, F. Rosenzweig thought F.W.J. Schelling was the author. No one has read this book for errors. As always, any errors, mistakes or oversights etc. are mine alone. Given a couple more years, I could improve this book. This is a philosophical translation and not a philological translation. Martin Luther who did the famous early translation of the Bible into German wrote in a letter, “If anyone does not like my translation, they can ignore it… (September 15, 1530)”. There are no ‘correct’ translations. Some are just better than other translations. -/- The Oldest Systematic Program of German Idealism. The German title is: Das Älteste Systemprogramm Des Deutschen Idealismus. This title was made up by Franz Rosenzweig in 1917, when he first published the manuscript. He found the manuscript in the Royal Library in Berlin in 1913. The manuscript suggested date is around 1796 and was done by handwriting research. However, the manuscript is not dated. The Prussian State Library auctioned in March 1913 from the auction of the house Liepmannssohn in Berlin a single sheet on the front and back with Hegel's cursive handwriting. The manuscript was lost during WWII. But Dieter Henrich found it again in 1979 in the “Biblioteka Jagiellonska” in Krakow (Poland), where it is today. Address: Jagiellonian Library, Jagiellonian University, al. Mickiewicza 22, 30-059 Cracow, Poland. Later research suggests that manuscript had come from the estate of Hegel’s student Friedrich Christoph Förster (1791-1868). He was one of the editors of Hegel’s posthumous works and most likely had access to a number of Hegel’s manuscripts. This text actually being one of them. Hegel traveled around Bohemia with Marie and Friedrich Christoph Förster around the year 1820-21 (see Klaus Vieweg). -/- Philosophical mystery -- who is the author or authors of this text? -/- Take a plunge into the deep and cold waters. Maybe a quagmire or quandary, but decidedly interesting. This project is to contextualize an old handwritten manuscript which is about 225 years old. The actual author is a mystery. I offer my own assessment. You can make your own assessments. The mystery has continued to unfold since 1917. There is plenty to read. Otherwise, think about the authorship and read more of the German philosophers and authors from this period and enjoy the depth of thinking and philosophizing. On one hand, there is just the sheer fun in the puzzle of the authorship questions; and on the other hand, these are the alluring thoughts that lead to the nascent stage of German Idealism and our intellectual heritage. There is no end to the accolades for this group of philosophers. A heritage that we still hear in in our attempts to move forward into our future. -/- Do your own astute exegesis (ἐξήγησις) as all paths are still open. Let your thought take to the wings of what is called thinking with this text. Critical encounters (Auseinandersetzung, or a Gegenüberstellung) with at least: Friedrich Hölderlin (1770-1843) Friedrich Wilhelm Joseph Schelling (1775-1854), and Georg Wilhelm Friedrich Hegel (1770-1831) --- starts here! German Idealism. We are not going to study this situation endlessly, instead we make some broad strokes and provide you a general context. You are allowed to read between the lines too. Goal: to understand the overall affinity and differences between the intellectuals of this period in German history; and to come to grips with this demanding text within its large scholarly context in the last 100 years. There are no final answers. (shrink)

Cambridge’deki büyük akademik cemaatin sakinleri olan bizler bir araya geldik ve hoşgörü ve onun egemen politik iklim içerisindeki yeri hakkında dostça ama ateşli bir tartışma yürüttük. Okuyucu, bizim nerelerde aynı düşüncede olmadığımızı bulmakta hiçbir zorluk çekmeyecektir. Diğer taraftan, farklı başlangıç noktalarından ve farklı yollardan hareketle yaklaşık olarak aynı yere ulaştık. Her birimiz için, egemen hoşgörü kuramı ve pratiğinin, incelendiği takdirde, korkunç politik gerçekleri gizlemeye yarayan bir maske olduğu ortaya çıktı. Kızgınlığın tonu makaleden makaleye keskin bir şekilde artmakta; belki de boş (...) yere, okuyucuların bu noktaya getiren akıl yürütmeyi takip edeceklerini umuyoruz. Nihayetinde bu kızgınlık hem kafa hem de kalpte ikamet etmektedir…. (shrink)

Never was dogmatic reductionism helpful in conceiving the phenomenon of life. The post-genomic era has made it clear that genes alone cannot explain the functioning of whole organisms. Already each cell represents a unique, non-recurring individual. Recent progress in developmental biology has conveyed new perspectives both on the makings of individual organisms (ontogeny), as on evolutionary change (Evo-Devo). The genome (the entirety of all genes) of an animal remains constant from fertilization onwards in each cell. The realization of genes requires (...) molecular environments, in particular pertinent to the cytoplasm of the unfertilized egg. Individuality of an organism therefore is not only determined by its genome, but is shaped through developmental processes (it needs time!). Organisms can only exist through mutual interplays with their respective (molecular and cellular) environments at all levels of organization. Thus, life can be conceived of as endless networks of communication, e.g. as a mutual continuum, connecting all individuals, all species and all generations within their given environments. Evolutionarily, nature does not select fitting genes, but rather viable traits. The presented concepts render it unlikely that it was genes that founded our living world, but rather that distinct environments shaped “genes” (of whatever chemical nature) which proved to be “life-suitable”. (shrink)

Most of us intuitively take discrimination based on gender or ethnicity to be impermissible because we have a right to be treated on the basis of merit and capacity rather than e.g. ethnicity or gender. I call this suggestion the Impermissibility Account. I argue that, despite how the Impermissibility Account seems intuitive to most of us with a humanist outlook, it is indefensible. I show that well-informed discrimination can sometimes be permissible, and even morally required, meaning we cannot have a (...) strict right not to be discriminated against. I then propose an alternative and more plausible account which I call the Fairness and Externalities Account, arguing that acts of discrimination are wrong partly because they are unfair and partly because they create harmful externalities which—analogously to pollution—there is a collective responsibility to minimize. Both of these factors are however defeasible, meaning that if the Fairness and Externalities Account is correct, then discrimination is sometimes permissible. These results are counterintuitive, and suggest that the ethics of discrimination requires further attention. (shrink)

We review some of the main implications of the free-energy principle (FEP) for the study of the self-organization of living systems – and how the FEP can help us to understand (and model) biotic self-organization across the many temporal and spatial scales over which life exists. In order to maintain its integrity as a bounded system, any biological system - from single cells to complex organisms and societies - has to limit the disorder or dispersion (i.e., the long-run entropy) of (...) its constituent states. We review how this can be achieved by living systems that minimize their variational free energy. Variational free energy is an information theoretic construct, originally introduced into theoretical neuroscience and biology to explain perception, action, and learning. It has since been extended to explain the evolution, development, form, and function of entire organisms, providing a principled model of biotic self-organization and autopoiesis. It has provided insights into biological systems across spatiotemporal scales, ranging from microscales (e.g., sub- and multicellular dynamics), to intermediate scales (e.g., groups of interacting animals and culture), through to macroscale phenomena (the evolution of entire species). A crucial corollary of the FEP is that an organism just is (i.e., embodies or entails) an implicit model of its environment. As such, organisms come to embody causal relationships of their ecological niche, which, in turn, is influenced by their resulting behaviors. Crucially, free-energy minimization can be shown to be equivalent to the maximization of Bayesian model evidence. This allows us to cast natural selection in terms of Bayesian model selection, providing a robust theoretical account of how organisms come to match or accommodate the spatiotemporal complexity of their surrounding niche. In line with the theme of this volume; namely, biological complexity and self-organization, this chapter will examine a variational approach to self-organization across multiple dynamical scales. (shrink)

John Schellenberg has advanced the hiddenness argument against God’s existence, based on the idea that an all-loving God would seek personal relationships. This paper develops a reply to Schellenberg’s argument by examining the notion of moral impurity, as understood by Paul the Apostle. Paul conceptualized moral impurity as a causal state that transfers from person to person, like a contagious disease. He also believed that moral impurity precludes divine-human relationship. The goal of this paper is to develop these (...) ideas into a problem for one Schellenberg’s key premises. (shrink)

DESENVOLVIMENTO EMBRIONÁRIO E DIFERENCIAÇÃO SEXUAL -/- E. I. C. da Silva Departamento de Agropecuária – IFPE Campus Belo Jardim Departamento de Zootecnia – UFRPE sede -/- 1.1 INTRODUÇÃO O sexo foi definido como a soma das diferenças morfológicas, fisiológicas e psicológicas que distinguem o macho da fêmea permitindo a reprodução sexual e assegurando a continuidade das espécies. Os processos de diferenciação sexual são realizados durante o desenvolvimento embrionário, onde ocorre a proliferação, diferenciação e maturação das células germinativas e primordiais, precursoras (...) de ovócitos e espermatozoides em fêmeas e machos, respectivamente. Assim, os embriões machos e fêmeas iniciam o seu desenvolvimento de forma semelhante, de modo que em ambos os sexos se estabelecem em estruturas idênticas a partir das quais se formarão os órgãos reprodutores correspondentes a cada sexo. O conhecimento da origem e do desenvolvimento do aparelho genital é indispensável para entender sua função e as alterações que produzem infertilidade ou esterilidade. 1.2 DETERMINAÇÃO DO SEXO CROMOSSÔMICO Nos mamíferos, o sexo cromossômico é determinado no momento da fertilização, quando um óvulo, que contém um cromossomo X, é fecundado por um espermatozoide portador de um cromossomo X ou um cromossomo Y. No primeiro caso, o complemento cromossômico seria XX, o que originaria uma fêmea (sexo homogamético), e no segundo daria como resultado um macho com a fórmula cromossômica XY (sexo heterogâmico). 1.3 A GÔNADA INDIFERENCIADA A primeira manifestação das gônadas se aprecia no embrião em forma de um par de eminências longitudinais chamadas cristas ou dobras gonodais, situadas em ambos os lados da linha média entre os mesonefros (rins em desenvolvimento) e do mesentério dorsal. Nos embriões dos mamíferos, as células germinativas primordiais (CGP) manifestam-se em estágios precoces do desenvolvimento, podendo ser detectadas pela primeira vez na metade da gastrulação. As CGP são células grandes, de citoplasma claro e núcleo grande e redondo, localizadas na parede do saco vitelino, perto do alantoide. Essas células possuem grande capacidade de proliferação e vão migrar desde o endoderma do intestino e o epitélio do saco vitelino, através do mesentério, até as cristas gonodais. Isso ocorre por volta do 26° dia da gestação no bovino. Sua migração realiza-se graças aos movimentos de translocação passiva e deslocamento ameboide ativo. Desconhece-se o mecanismo pelo qual estas células são dirigidas para as cristas gonodais, porém foram estudadas algumas moléculas que se expressam durante sua migração e que poderiam desempenhar um papel importante na diferenciação deste tipo celular. A fosfatase alcalina é uma enzima que tem sido usada como marcador de CGP para determinar a sua origem e migração. Num estudo recente, foi inserido um marcador fluorescente que se exprime unicamente nas células germinativas primordiais de embriões transgênicos, e utilizando este marcador e a fosfatase alcalina determinou-se a origem e o padrão de migração destas células. O primeiro sinal de diferenciação das células germinativas primordiais é a expressão de fosfatase alcalina, e esta apareceu pela primeira vez na parte mais posterior da linha primitiva. No sétimo dia de desenvolvimento no embrião do camundongo, o endoderma visceral (AF+) é substituído pelo endoderma definitivo (AF-) originado na parte anterior da linha primitiva. O fator de transcrição Oct-4 é expresso nas CGP de ambos os sexos, pelo que acredita-se estar envolvido na mantença a totipotêncialidade das células. O receptor tirosina quinase, cujo ligante é o fator de Steel, é outra das moléculas que expressam as CGP. Tem sido demonstrado que este receptor possui um papel muito importante na sobrevivência deste tipo celular. Existem outros fatores que promovem a sobrevivência e/ou proliferação de CGP in vitro. Em experiências realizadas com o fator de transformação beta I (TGFβ-I), observou-se que este tem um efeito negativo sobre a proliferação das CGP. Outra atividade que tem sido postulada a este fator é o de um agente quimioatraente que possivelmente possa direcionar a migração destas células para a gônada. a) Um formado pelas células germinativas primordiais (precursoras dos gametas masculinos ou femininos), rodeadas de células somáticas das quais posteriormente se derivarão as células de Sertoli no macho e as células da granulosa na fêmea. b) O tecido que formará o estroma da gônada: tecido conjuntivo, vasos sanguíneos e as células intersticiais com atividade esteroidogênica (células de Leydig no testículo e a teca interna do ovário). As células somáticas do primórdio gonodal originam-se do mesoderma. Inicialmente são de três tipos: mesenquimáticas, mesoteliais e endoteliais. As células mesenquimáticas e mesoteliais iniciam grande atividade proliferativa ao chegar as CGP. Observa-se então uma condensação de células de origem mesotelial e mesenquimatoso que forma um agregado compacto denominado "blastema gonodal". A partir deste primórdio embrionário, diferenciam-se dois tecidos gonodais: os cordões sexuais e o estroma. Os cordões sexuais são arranjos epiteliais que se encontram delimitados por uma folha basal, e dentro deles encontramos as CGP. Por sua vez, no estroma encontram-se células do tipo mesenquimático e vasos sanguíneos. Neste momento, as gônadas são indiferenciadas e bipotencialmente sexuais, sendo impossível diferenciar, morfologicamente, uma gônada masculina de uma feminina, mas no caso dos machos genéticos já existe uma diferenciação da gônada a nível molecular. Nesta fase já se encontram presentes as estruturas das quais se desenvolvem os dutos mesonéfricos ou de Wolff precursores do aparelho genital masculino e os dutos paramesonéfricos ou de Müller que darão origem ao aparelho reprodutor feminino. Há uma série de fatores envolvidos no desenvolvimento precoce da gônada, entre os quais o fator esteroidogênico I (SFI: Steroidogenic fator l), que é um membro da subfamília de receptores nucleares, receptores órfãos. Este fator de transcrição tem um local de ligação ao DNA composto por dois dedos-de-Zinc. O SFI foi identificado como um ativador de genes envolvidos na biossíntese de esteroides em diferentes células. O SFI está presente durante o desenvolvimento embrionário em regiões associadas com funções endócrinas como gônadas, adrenais, pituitárias e hipotálamos. Os animais homozigotos para o gene SFI defeituoso, necessitam de gônadas e adrenais e têm a função gonadotrófica alterada. Os ratos sem SFI carecem de gonadotrofos e têm um desenvolvimento anormal do núcleo ventro-medial do hipotálamo; em particular as gônadas deixam de se desenvolver entre os dias 11 a 15 e degeneram-se por apoptose. No entanto, a crista genital forma-se e é colonizada pelas células germinativas, o que indica que estas continuam a receber o sinal adequado para a sua migração. Portanto, o SFI não está envolvido no desenvolvimento precoce da gônada e do sistema urogenital, mas parece estar envolvido na manutenção do crescimento das células somáticas presentes na gônada indiferenciada. O gene associado ao tumor de Wilms (WTI: Wilm's tumor Associated) está envolvido no desenvolvimento da gônada e do rim. Durante o desenvolvimento embrionário, WTI se expressa em todo o mesoderma intermediário e posteriormente na gônada indiferenciada, bem como no rim em formação. WTI regula o sinal indutivo do mesênquima para o epitélio celômico dos mesonefros. Se este for o caso, então WTI é responsável pelo crescimento da crista genital ao dirigir a entrada do epitélio celômico. Dado que estas células darão origem às células de Sertoli, a carência de WTI pode causar o desenvolvimento de embriões XY como fêmeas simplesmente porque não se formam as células de Sertoli. Em geral, todos os genes importantes na diferenciação do mesoderma intermediário e do sistema urogenital intervêm no desenvolvimento da gônada precoce. 1.4 DIFERENCIAÇÃO GONODAL O desenvolvimento das gônadas e ductos genitais descritos até o momento, é o mesmo para ambos os sexos. Igualmente, os genes descritos, que estão envolvidos no desenvolvimento das gônadas, ductos genitais e migração das células germinativas, afetam igualmente os embriões com genótipo XX ou XY. A gônada primitiva consiste anatomicamente de uma medula (interna) e uma crosta (externa), e de acordo com o local onde ocorre a colonização das células germinativas, diferenciara em testículo ou um ovário, respectivamente. Nos mamíferos, a primeira manifestação estrutural de diferenciação sexual é detectada na gônada dos machos, onde as células germinativas estão localizadas na medula. A diferenciação do testículo inicia-se quando os cordões sexuais se separam do epitélio celômico como consequência dos arranjos produzidos por uma invasão do mesênquima e vasos sanguíneos que provoca a compactação dos cordões, agora denominados cordões testiculares. As células que rodeiam os cordões se achatam e formam as células mioides, que são responsáveis pela formação das membranas basais. As células do epitélio interno, ou seja, as células de Sertoli, têm duas funções principais: o suporte das CGP e a síntese da hormona antimulleriana, responsável pela regressão dos ductos de Müller e secretada durante o período de diferenciação sexual. As células do estroma que rodeiam os cordões testiculares diferenciam-se para formar vários tipos de células: células mioides, fibroblastos, endotélio e células de Leydig, que são as mais importantes pela sua atividade endócrina. Posteriormente, os cordões testiculares dão origem aos túbulos seminíferos, que contêm o epitélio que produzirá os espermatozoides ao chegar à puberdade. Na fêmea, durante os estágios iniciais de diferenciação gonodal, não se observam mudanças em relação à gônada indiferenciada, só pode-se observar um certo crescimento devido à proliferação de células somáticas e germinativas. As células germinativas iniciam um período de proliferação, que termina com o início da meiose. Iniciada a meiose, dá-se o processo de foliculogênese; neste momento os cordões epiteliais se fragmentam, de tal maneira que cada ovócito fica rodeado de células epiteliais cobertas por uma folha basal fina (figura 1). Para que a gônada primitiva se desenvolva em testículo é indispensável a presença do cromossoma Y, independentemente do número de cromossomas X que contenha o genoma de um indivíduo. O gene determinante do testículo encontra-se localizado no cromossoma Y, denominado sry em ratos e SRY em humanos. O gene sry se expressa durante o desenvolvimento embrionário na crista genital de embriões de camundongos. A expressão é detectável no dia 10,5, pouco depois do aparecimento das cristas genitais, atinge o seu máximo durante o dia 11,5 e mantém-se até pouco depois de ocorrerem os primeiros sinais morfológicos de diferenciação testicular no dia 12,5. Este padrão de expressão é compatível com a teoria de que sry atua induzindo a ativação dos genes (figura 2) que conduzem ao desenvolvimento testicular, sem que exista a necessidade da expressão contínua de sry para manter a diferenciação do testículo após o dia 12,5. Como mencionado anteriormente, a gônada primitiva é composta por vários tipos de células. No entanto, as células germinativas primordiais não são o local de expressão do sry, já que os embriões que necessitam de células germinativas mantêm a expressão de sry e desenvolvem o sexo gonodal normalmente. As células somáticas na gônada em desenvolvimento incluem também as células de suporte. Sabe-se que é nestas células que o sry é expresso para que se diferenciem em células de Sertoli, e a expressão transitória de sry indica que deve ativar a outros genes para a manutenção das células de Sertoli. Uma vez diferenciadas as células de Sertoli, elas se encarregarão da diferenciação do resto das células na gônada. -/- Figura 1: Representação da diferenciação dos órgãos genitais internos. Adaptado de BRONSON, 1989. Figura 2: Cascada de genes envolvidos na diferenciação sexual, adaptado de KOOPMAN, 1999. O fator sry é necessário para a diferenciação do testículo. Embora não se conheçam os genes que provavelmente regulam esse gene, estudos realizados em camundongos demonstram que este gene parece coordenar-se com certos genes autossômicos. Entre estes genes autossômicos, o sox9, que é produzido pelas células de Sertoli uma vez que são estimuladas por sry, de modo que sox9 é um dos genes relacionados estruturalmente com sry. O Sox9 funciona como um fator de transcrição, mas não se sabe se a proteína tem qualquer outra função estrutural; este gene exprime-se abundantemente nos condrócitos e está relacionado com defeitos do aparelho ósseo chamados displasia campomélica. Curiosamente, os pacientes XY com esta condição sofrem frequentemente de reversão do sexo. O Sox9 é um dos poucos genes, além do SRY, do qual as mutações demonstraram interferir com a determinação sexual masculina. No entanto, apenas 75% dos pacientes com anomalias esqueléticas de tipo displasia campomélica têm reversão sexual e não foram encontrados casos de reversão sexual devido a um defeito de Sox9 que não seja acompanhado de defeitos esqueléticos. Isso indica que o Sox9 é apenas um membro da rede de genes que são ativados para determinar a diferenciação sexual, enquanto a rota que rege a condrogênese é mais sensível a perturbações deste. O momento em que se detecta a expressão do gene Sox9 (11dpc em ratos) coincide com a máxima expressão de sry, o que poderia indicar a possibilidade de que sry regule positivamente a Sox9. De fato, na região do promotor de Sox9 há um local de união ao que potencialmente se pode unir o sry. A expressão de Sox9 durante a diferenciação sexual sugere um papel abaixo de sry na diferenciação das células de Sertoli. O cromossoma X também é importante na diferenciação gonodal. O gene DAX-I foi isolado do lócus DSS (Dosage sensitive sex reversal) do cromossoma X. DAX-I é parte da cascata de determinação sexual, mas não é necessário para a formação do testículo. DAX-I é um membro dos receptores nucleares conhecidos como receptores órfãos. Este gene demonstrou ser um poderoso repressor da transcrição de SFI e de vários genes. Os padrões de expressão de DAX-I são complementares daqueles de SFI, ambos expressos nas cristas genitais. Em resumo, dada a evidência exposta, desenvolveu-se a hipótese de que DAX-I é um antagonista de sry; esse antagonismo é dependente dos níveis relativos de DAX-I e sry e de um limiar que varia de espécie para espécie. A DAX-I foi classificada como o gene antitestículo. Na fêmea (cariótipo XX) é importante que ocorra a inativação de um dos cromossomas sexuais X para que se mantenha o equilíbrio genético ao igualar o conteúdo de DNA dos cromossomas. Esse cromossoma inativado constitui o chamado corpúsculo de Barr. No entanto, para que a meiose se realize, é necessário dos dois cromossomas X ativos nos ovócitos para assegurar a diferenciação ovárica e a fertilidade. 1.5 DIFERENCIAÇÃO DOS DUCTOS SEXUAIS O embrião possui, além das gônadas indiferenciadas, dois sistemas de ductos: os de potencialidade masculina denominam-se ductos de Wolff ou mesonéfricos, e os de potencialidade feminina se chamam ductos de Müller ou paramesonéfricos (figura 1). Se a diferenciação gonodal levou à formação de um testículo, a partir do ducto mesonéfrico ou de Wolff se desenvolverão os ductos eferentes, o epidídimo, os ductos deferentes e as vesículas seminais. As hormonas importantes no desenvolvimento do aparelho genital masculino são a testosterona, produzida pelas células de Leydig, e sua forma 5α reduzida, a 5α di-hidrotestosterona. Acredita-se que a testosterona é responsável pela virilização dos ductos de Wolff, e a di-hidrotestosterona dos órgãos genitais externos. No macho, os canais de Müller atrofiam-se devido à ação de uma hormona fetal de origem testicular denominada hormona inibidora das estruturas de Müller (HIM) ou hormona antimulleriana. Este processo começa assim que os cordões espermáticos se formam e se diferenciam as células de Sertoli. A existência de HIM foi proposta baseada em estudos realizados em bezerras freemartin, devido à existência de uma hormona responsável pela atresia dos ductos de Müller que na fêmea dá origem ao útero e aos ovidutos. Essa hormona provoca a involução do aparelho genital do bovino nas gestações gemelares nas quais os produtos de diferente sexo têm comunicação sanguínea por ter ocorrido a anastomose dos vasos de ambas as placentas (figura 3). A HIM é uma glicoproteína pertencente à subfamília de TGFβ, é expressa pelas células que darão origem às células de Sertoli e é um dos primeiros marcadores de diferenciação nestas células. A HIM é secretada na vida adulta pelas células de Sertoli no testículo e por células da granulosa no ovário. No rato a HIM é expressa-se no 12° dia em um teste padrão que segue muito de perto o aumento na expressão de sry. No macho, esta secreção de HIM continua durante a vida fetal e adulta, contudo os níveis de HIM declinam na puberdade devido a um aumento na secreção de testosterona. Vários fatores intervêm na regulação do gene de HIM, incluindo os acima descritos SFI e Sox9. O gene HIM contém segmentos de DNA que são conservados em várias espécies de vertebrados. Existe um nexo de ligação para SFI, que ativa a transcrição de HIM. A mutação no local de ligação de SFI resulta em reversão do sexo em indivíduos XY incluindo genitais femininos normais, presença de um útero formado enfatizando a importância de SFI na determinação sexual e na expressão de HIM. Embora SFI seja um bom candidato como regulador de HIM, é expresso em outras células, como as de Leydig e adrenais, que não expressam HIM. Em contrapartida, Sox9 é expresso unicamente nas células de Sertoli que são as produtoras de HIM. O gene HIM também tem um nexo de ligação para Sox9. Além disso, Sox9 pode atuar sinergicamente com SFI para promover a secreção de HIM. Ao contrário destes dois fatores de transcrição, DAX-I antagoniza a ação de Sox9 e provavelmente SFI sobre o promotor de HIM. Assim, para que as células de Sertoli secretem HIM, a transcrição de DAX-I deve diminuir. Figura 3: Representação da diferenciação dos órgãos genitais externos. Adaptado de BRONSON, 1989. Os ductos de Wolff tornam-se o sistema de ejaculação do macho. A porção mais próxima dos testículos dá origem ao epidídimo, a parte central ao ducto deferente e a porção mais distal às vesículas seminais. A próstata e a parte membranosa da uretra do macho desenvolvem-se a partir da porção pélvica do seio urogenital. A virilização e diferenciação dos ductos de Wolff dependem da produção de testosterona pelo testículo. Quanto aos órgãos genitais externos do macho, o tubérculo genital é ampliado e as dobras uretrais se fundem para formar a uretra peniana. A fusão das dobras uretrais aproxima os tubérculos genitais para formar o escroto (figura 4). Figura 4: Diferenciação do aparelho genital da fêmea e do macho. Adaptado de KOOPMAN, 1989. A diferenciação dos órgãos genitais da fêmea ocorre de forma passiva, já que a ausência de testículos e por isso da hormona inibidora dos ductos de Müller (HIM), assim como dos andrógenos virilizantes, favorece o desenvolvimento dos ductos de Müller, enquanto os de Wolff sofrem atrofia. A porção cefálica dos ductos de Müller dá origem aos ovidutos, que na sua terminação caudal se fundem com o útero. O contato dos ductos de Müller com o seio urogenital induz uma intensa proliferação celular que resulta na formação da área uterovaginal localizado entre o seio urogenital e os ductos de Müller. As células do prato uterovaginal proliferam e aumentam a distância entre as duas estruturas criando o espaço que formará a vagina quando o prato é canalizado e forma um lúmen. Em contraste com o que ocorre no macho, na fêmea a maior parte do seio urogenital se mantém exposta na superfície da abertura onde desembocam a vagina e a uretra. O tubérculo urogenital da fêmea tem um crescimento limitado e forma o clitóris. A sequência de passos da diferenciação sexual do aparelho genital é resumida na tabela 1. Tabela 1: Destino em desenvolvimento dos rudimentos sexuais dos fetos macho e fêmea dos mamíferos -/- Rudimento sexual Macho Fêmea Gônada Testículo Ovário Ductos de Müller (Paramesonéfricos) Vestígios Útero, parte da vagina, ovidutos Ductos de Wolff (Mesonéfricos) Ductos eferentes deferentes, epidídimo, vesículas seminais Vestígios Seio urogenital Uretra, próstata, glândulas bulbouretrais Parte da vagina, uretra, vestíbulo, glândulas vestibulares Tubérculo genital Pênis Clitóris Pregas vestibulares Escroto Lábios vulvares Fonte: HAFEZ, 2004. 1.6 DIFERENCIAÇÃO SEXUAL DO HIPOTÁLAMO Os processos de diferenciação sexual não se limitam apenas às células somáticas do organismo do feto, mas incluem também os centros nervosos superiores do cérebro. Assim, da mesma maneira que a gônada e os ductos sexuais se desenvolvem para o tipo feminino ou masculino, propôs-se que o cérebro pode ser "masculinizado" ou permanecer "Feminizado". A diferenciação do hipotálamo vai depender do ambiente esteroidal do neonato e ocorre na fase perinatal. Estes eventos serão de grande transcendência na vida reprodutiva do indivíduo. Tanto a fêmea como o macho nascem com a capacidade de secreção de gonadotropinas de acordo com um padrão cíclico; contudo, no macho, a exposição do hipotálamo à ação dos andrógenos testiculares durante os primeiros dias da vida extrauterina provoca a masculinização, com o qual o hipotálamo do macho é programado para que a secreção de gonadotropinas se realize a um ritmo relativamente constante por parte da hipófise (secreção tônica). Na fêmea, tanto a secreção tônica como a cíclica se conservam. No entanto, observou-se que a injeção de testosterona ou o transplante de testículo na rata fêmea durante os primeiros dias de vida, suprime a sua futura atividade estral (secreção cíclica). Por outro lado, se os ovários forem transplantados para o rato macho normal castrado na idade adulta, o animal não desenvolve qualquer atividade cíclica, mas se os machos transplantados forem castrados ao nascer, o ovário é capaz de efetuar mudanças cíclicas e ovulações. Isto foi demonstrado em roedores, mas não em animais domésticos ou na espécie humana. Portanto, o padrão de secreção de gonadotropinas, seja cíclico ou tônico, não depende da hipófise, mas do hipotálamo e sua correta diferenciação. 1.7 CONCLUSÕES A maioria dos conhecimentos no campo da biologia do desenvolvimento e, muito especificamente, dos processos de diferenciação sexual têm sido originados de estudos relacionados com desordens congênitas, que na sua maioria devem-se a defeitos de genes específicos. A análise detalhada destas desordens permitiu entender alguns mecanismos endócrinos, moleculares e genéticos envolvidos na diferenciação sexual. A identificação do gene sry como determinante do testículo foi uma contribuição crucial e abriu as portas à compreensão dos mecanismos moleculares e celulares relacionados com o desenvolvimento do testículo. Se este gene não estiver presente, é criado um programa genético alternativo para levar a cabo a diferenciação gonodal para o ovário. Finalmente, devemos ter presente que é necessária uma correlação entre mudanças morfológicas e expressão de genes durante o desenvolvimento para entender os mecanismos relacionados com a diferenciação. -/- Apoio -/- Realização -/- REFERÊNCIAS BIBLIOGRÁFICAS ANDERSON, Robert et al. The onset of germ cell migration in the mouse embryo. Mechanisms of development, v. 91, n. 1-2, p. 61-68, 2000. AUSTIN, Colin Russell; SHORT, R. V. Reproduction in Mammals: Volume 1, Germ Cells and Fertilization. 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Mullerian inhibiting substance activity in bovine fetal, newborn and prepubertal testes. Biology of reproduction, v. 16, n. 2, p. 238-243, 1977. HAFEZ, Elsayed Saad Eldin; HAFEZ, B. Reprodução animal. São Paulo: Manole, 2004. HANLEY, Neil A. et al. Steroidogenic factor 1 (SF-1) is essential for ovarian development and function. Molecular and cellular endocrinology, v. 163, n. 1-2, p. 27-32, 2000. HIORT, Olaf; PAUL-MARTIN, H. The molecular basis of male sexual differentiation. European journal of endocrinology, v. 142, n. 2, p. 101-110, 2000. HOLY, Lubos; MARTÍNEZ JÚSTIZ, G. Colab. Biología de la reproducción bovina. Havana: Revolucionária, 1975. JOSSO, Nathalie et al. The role of anti-Müllerian hormone in gonadal development. Molecular and cellular endocrinology, v. 145, n. 1-2, p. 3-7, 1998. JOST, Alfred et al. Studies on sex differentiation in mammals. In: Proceedings of the 1972 Laurentian Hormone Conference. Londres: Academic Press, 1973. p. 1-41. KNOBIL, Ernst. Knobil and Neill's physiology of reproduction. EUA: Gulf Professional Publishing, 2006. KOFMAN ALFARO, S.; MERCHANT LARIOS, H.; PEREZ PALACIOS, G. Diferenciacion sexual. I. Bases biologicas del dimorfismo sexual. Rev. invest. clín, p. 349-59, 1982. KOOPMAN, Peter. Sry and Sox9: mammalian testis-determining genes. Cellular and Molecular Life Sciences CMLS, v. 55, n. 6-7, p. 839-856, 1999. MCDONALD, L. E. Veterinary endocrinology. Lea & Febiger, Philadelphia, Pa, 1969. MEIZEL, S.; JOHNSON, M. H. Development in mammals. MH Johnson, Ed, v. 3, p. 1-64, 1978. MELLO, Maricilda Palandi de; ASSUMPÇÃO, Juliana de G.; HACKEL, Christine. Genes envolvidos na determinação e diferenciação do sexo. Arquivos Brasileiros de Endocrinologia & Metabologia, v. 49, n. 1, p. 14-25, 2005. -/- REFERÊNCIAS BIBLIOGRÁFICAS MERCHANT-LARIOS, H. Ovarian differentiation. The Vertebrate Ovary, p. 47-81, 1978. MIES FILHO, Antonio. Reprodução dos animais. Porto Alegre: Sulina, 1987. NEF, Serge; PARADA, Luis F. Hormones in male sexual development. Genes & Development, v. 14, n. 24, p. 3075-3086, 2000. PARKER, Keith L.; SCHEDL, Andreas; SCHIMMER, Bernard P. Gene interactions in gonadal development. Annual review of physiology, v. 61, n. 1, p. 417-433, 1999. SWAIN, Amanda; LOVELL-BADGE, Robin. Mammalian sex determination: a molecular drama. Genes & development, v. 13, n. 7, p. 755-767, 1999. WILHELM, Dagmar; PALMER, Stephen; KOOPMAN, Peter. Sex determination and gonadal development in mammals. Physiological reviews, v. 87, n. 1, p. 1-28, 2007. WILSON, Jean D.; GRIFFIN, James E.; GEORGE, Fredrick W. Sexual differentiation: early hormone synthesis and action. Biology of reproduction, v. 22, n. 1, p. 9-17, 1980. -/- Emanuel Isaque Cordeiro da Silva Belo Jardim, 07 de Maio de 2020. (shrink)

In this paper, I explore a tension between the Law in the novel The Island of Doctor Moreau, by H. G. Wells, and Kant's reciprocity thesis. The Law is a series of prohibitions that Moreau has his beasts recite. Moreau devotes his time to transforming animals through a painful surgery into beings that resemble humans, but the humanized beasts are constantly slipping back into animalistic habits, and so Moreau promulgates the Law to maintain decorum. Kant's reciprocity thesis states that free (...) will is the necessary and sufficient condition of moral practical laws. That is, in order for a moral practical law to be applicable, there must be free will, and, if free will is present, then there will be a moral practical law that sets a standard for the free will. However, in Wells's novel, the humanized beasts seem to lack free will. So, how can a law be applicable to them? By delving deeper into the mystery of Moreau's strange island, I will shed light on the otherwise cumbersome concepts of free will, natural impulses, and practical laws, as well as their interrelationships. The upshot will be a deeper understanding of personhood through an exploration of the instinctual nature of animals, moral law, and free will. (shrink)

We present a game mechanic called pseudo-visibility for games inhabited by non-player characters (NPCs) driven by reinforcement learning (RL). NPCs are incentivized to pretend they cannot see pseudo-visible players: the training environment simulates an NPC to determine how the NPC would act if the pseudo-visible player were invisible, and penalizes the NPC for acting differently. NPCs are thereby trained to selectively ignore pseudo-visible players, except when they judge that the reaction penalty is an acceptable tradeoff (e.g., a guard might accept (...) the penalty in order to protect a treasure because losing the treasure would hurt even more). We describe an RL agent transformation which allows RL agents that would not otherwise do so to perform some limited self-reflection to learn the training environments in question. (shrink)

Bu kitap, Carl Schmitt'in demokrasi ve diktatörlük üzerine düşüncelerini politik felsefenin sorgu sahasında ele almayı amaçlayarak Schmitt'i kendi döneminin polemikleri arasında konumlandırmaktadır. Bu amaçla Weimar dönemi hukukçuları üzerinde önemli etkisi olan Carl Friedrich Wilhelm von Gerber ve Paul Laband'ın anayasa düşünceleri ekseninde Alman İmparatorluğu'nun hukuk mirası incelenmiştir. Weimar Cumhuriyeti'nin krizlerle şekillenen politik atmosferi, politik felsefe açısından verimli tartışmaların ortaya çıkmasını sağlamıştır. Bu tartışmaların izi; dönemin hukukçularından Gerhard Anschütz, Richard Thoma, Georg Jellinek, Hans Kelsen ve Hermann Heller'ın demokrasi ve (...) diktatörlük tartışmasına kaynaklık eden düşünceleri üzerinden sürülmüştür. Schmitt, çoğunluğu 1920'li yıllara denk gelen anayasa hukuku çalışmaları ile Weimar dönemi hukuk tartışmaları arasında belirleyici bir yerde durmaktadır. Schmitt ile anayasanın koruyuculuğu ve parlamentarizm hakkında polemiğe giren düşünürler, kitabın ayrı bir bölümünün konusunu oluşturmaktadır. Politik felsefenin güncel bir uğrağı olmayı sürdüren Schmitt'in demokrasi ve diktatörlük üzerine düşünceleri, çağdaş dünyanın karşı karşıya kaldığı demokrasi sorunlarının derinleştirilmesinde verimli bir kaynaktır. Bu kitabın amaçları arasında, kendi tarihsel bağlamı içerisinde Schmitt'in devlet düşüncesinin spesifik bir incelemesini yapmanın yanında, kendisini diktatörlüğün karşısında konumlandıran liberal demokrasi anlayışını tartışmaya açmak da bulunmaktadır. (shrink)

The enigma of the Emergence of Natural Languages, coupled or not with the closely related problem of their Evolution is perceived today as one of the most important scientific problems. The purpose of the present study is actually to outline such a solution to our problem which is epistemologically consonant with the Big Bang solution of the problem of the Emergence of the Universe}. Such an outline, however, becomes articulable, understandable, and workable only in a drastically extended epistemic and scientific (...) oecumene, where known and habitual approaches to the problem, both theoretical and experimental, become distant, isolated, even if to some degree still hospitable conceptual and methodological islands. The guiding light of our inquiry will be Eugene Paul Wigner's metaphor of ``the unreasonable effectiveness of mathematics in natural sciences'', i.e., the steadily evolving before our eyes, since at least XVIIth century, ``the miracle of the appropriateness of the language of mathematics for the formulation of the laws of physics''. Kurt Goedel's incompleteness and undecidability theory will be our guardian discerner against logical fallacies of otherwise apparently plausible explanations. John Bell's ``unspeakableness'' and the commonplace counterintuitive character of quantum phenomena will be our encouragers. And the radical novelty of the introduced here and adapted to our purposes Big Bang epistemological paradigm will be an appropriate, even if probably shocking response to our equally shocking discovery in the oldest among well preserved linguistic fossils of perfect mathematical structures outdoing the best artifactual Assemblers. (shrink)