The Ontology for Biomedical Investigations (OBI) is an ontology that provides terms with precisely defined meanings to describe all aspects of how investigations in the biological and medical domains are conducted. OBI re-uses ontologies that provide a representation of biomedical knowledge from the Open Biological and Biomedical Ontologies (OBO) project and adds the ability to describe how this knowledge was derived. We here describe the state of OBI and several applications that are using it, such as adding semantic expressivity to (...) existing databases, building data entry forms, and enabling interoperability between knowledge resources. OBI covers all phases of the investigation process, such as planning, execution and reporting. It represents information and material entities that participate in these processes, as well as roles and functions. Prior to OBI, it was not possible to use a single internally consistent resource that could be applied to multiple types of experiments for these applications. OBI has made this possible by creating terms for entities involved in biological and medical investigations and by importing parts of other biomedical ontologies such as GO, Chemical Entities of Biological Interest (ChEBI) and Phenotype Attribute and Trait Ontology (PATO) without altering their meaning. OBI is being used in a wide range of projects covering genomics, multi-omics, immunology, and catalogs of services. OBI has also spawned other ontologies (Information Artifact Ontology) and methods for importing parts of ontologies (Minimum information to reference an external ontology term (MIREOT)). The OBI project is an open cross-disciplinary collaborative effort, encompassing multiple research communities from around the globe. To date, OBI has created 2366 classes and 40 relations along with textual and formal definitions. The OBI Consortium maintains a web resource providing details on the people, policies, and issues being addressed in association with OBI. (shrink)

The Repugnant Conclusion served an important purpose in catalyzing and inspiring the pioneering stage of population ethics research. We believe, however, that the Repugnant Conclusion now receives too much focus. Avoiding the Repugnant Conclusion should no longer be the central goal driving population ethics research, despite its importance to the fundamental accomplishments of the existing literature.

This thesis contends that the possession of a sense of humour would contribute considerably to the quality of human life. It is an exploration and discussion of some of the difficulties involved in justifying the development of humour in terms of a philosophy of education. In light of developments in the digital age with consequent changes in science, technology and society, the educated person of the future will have to be less concerned with the accumulated knowledge of the past than (...) with the development and interplay of social and natural environments. Such a person will need to have, more than ever, a sense of what is truly real and what is truly valuable in human life. If the primary purpose of education is the preparation of students for their future lives, educators are now faced with some challenging problems. Apart from the high social value of laughter, there is a recognized relationship between humour and intelligence. Knowing that the two are related proves to be a key factor in understanding the learning process and assuring that the development of a sense of humour in education is worthy of consideration. (shrink)

In various writings Michel Foucault has shown how, in the beginning of the 19th century, in settings such as army barracks, psychiatric hospitals and penitentiary institutions, the modern human sciences were ‹born› as an ensemble of disciplines (medical biology, psychiatry, psychology, criminology, and the like) From the beginning, the nature-nurture de- bate has been one of its key disputes. Are human individuals malleable by environmental factors (such as psychiatric treatments or disciplinary regimes), or do they rather display inborn predispositions for (...) delin- quency and other forms of antisocial behaviour? In the current era of genetic testing, in behavioural genomics and neuroscience, this issue is as controversial and topical as ever. Büchner’s unfinished drama Woyzeck (written in 1836) is a remarkable anticipation of this debate, staging the birth of the human individual as a research subject. It is the story of a destitute soldier who, according to his superiors, displays er- rant behaviour and is therefore recruited to serve as a research subject in an experiment. His army physician turns him into a ‹case›, which can be meticulously monitored and studied so as to record the genesis of a crime. In this paper, Büchner’s unsettling play is analysed in detail as one of the great anticipatory literary documents of the 19th century, ex- ploring the idea of predictive psychiatry and the quest for genetic pre- dispositions: a primal scene as it were of the nature-nurture debate as it unfolds from predictive criminology up to behavioural genomics. (shrink)

continent. 1.1 : 3-13. / 0/ – Introduction I want to propose, as a trajectory into the philosophically weird, an absurd theoretical claim and pursue it, or perhaps more accurately, construct it as I point to it, collecting the ground work behind me like the Perpetual Train from China Mieville's Iron Council which puts down track as it moves reclaiming it along the way. The strange trajectory is the following: Kant's critical philosophy and much of continental philosophy which has followed, (...) has been a defense against horror and madness. Kant's prohibition on speculative metaphysics such as dogmatic metaphysics and transcendental realism, on thinking beyond the imposition of transcendental and moral constraints, has been challenged by numerous figures proceeding him. One of the more interesting critiques of Kant comes from the mad black Deleuzianism of Nick Land stating, “Kant’s critical philosophy is the most elaborate fit of panic in the history of the Earth.” And while Alain Badiou would certainly be opposed to the libidinal investments of Land's Deleuzo-Guattarian thought, he is likewise critical of Kant's normative thought-bureaucracies: Kant is the one author for whom I cannot feel any kinship. Everything in him exasperates me, above all his legalism—always asking Quid Juris? Or ‘Haven’t you crossed the limit?’—combined, as in today’s United States, with a religiosity that is all the more dismal in that it is both omnipresent and vague. The critical machinery he set up has enduringly poisoned philosophy, while giving great succour to the academy, which loves nothing more than to rap the knuckles of the overambitious [….] That is how I understand the truth of Monique David-Menard’s reflections on the properly psychotic origins of Kantianism. I am persuaded that the whole of the critical enterprise is set up to to shield against the tempting symptom represented by the seer Swedenborg, or against ‘diseases of the head’, as Kant puts it. An entire nexus of the limits of reason and philosophy are set up here, namely that the critical philosophy not only defends thought from madness, philosophy from madness, and philosophy from itself, but that philosophy following the advent of the critical enterprise philosophy becomes auto-vampiric; feeding on itself to support the academy. Following Francois Laruelle's non-philosophical indictment of philosophy, we could go one step further and say that philosophy operates on the material of what is philosophizable and not the material of the external world. [1] Beyond this, the Kantian scheme of nestling human thinking between our limited empirical powers and transcendental guarantees of categorical coherence, forms of thinking which stretch beyond either appear illegitimate, thereby liquefying both pre-critical metaphysics and the ravings of the mad in the same critical acid. In rejecting the Kantian apparatus we are left with two entities – an unsure relation of thought to reality where thought is susceptible to internal and external breakdown and a reality with an uncertain sense of stability. These two strands will be pursued, against the sane-seal of post-Kantian philosophy by engaging the work of weird fiction authors H.P. Lovecraft and Thomas Ligotti. The absolute inhumanism of the formers universe will be used to describe a Shoggothic Materialism while the dream worlds of the latter will articulate the mad speculation of a Ventriloquil Idealism. But first we must address the relation of philosophy to madness as well as philosophy to weird fiction. /1/ – Philosophy and Madness There is nothing that the madness of men invents which is not either nature made manifest or nature restored. Michel Foucault. Madness and Civilization. The moment I doubt whether an event that I recall actually took place, I bring the suspicion of madness upon myself: unless I am uncertain as to whether it was not a mere dream. Arthur Schopenhauer. The World as Will and Idea, Vol. 3. Madness is commonly thought of as moving through several well known cultural-historical shifts from madness as a demonic or otherwise theological force, to rationalization, to medicalization psychiatric and otherwise. Foucault's Madness and Civilization is well known for orientating madness as a form of exclusionary social control which operated by demarcating madness from reason. Yet Foucault points to the possibility of madness as the necessity of nature at least prior to the crushing weight of the church. Kant’s philosophy as a response to madness is grounded by his humanizing of madness itself. As Adrian Johnston points out in the early pages of Time Driven pre-Kantian madness meant humans were seized by demonic or angelic forces whereas Kantian madness became one of being too human. Madness becomes internalized, the external demonic forces become flaws of the individual mind. Foucault argues that, while madness is de-demonized it is also dehumanized during the Renaissance, as madmen become creatures neither diabolic nor totally human reduced to the zero degree of humanity. It is immediately clear why for Kant, speculative metaphysics must be curbed – with the problem of internal madness and without the external safeguards of transcendental conditions, there is nothing to formally separate the speculative capacities for metaphysical diagnosis from the mad ramblings of the insane mind – both equally fall outside the realm of practicality and quotidian experience. David-Menard's work is particularly useful in diagnosing the relation of thought and madness in Kant's texts. David-Menard argues that in Kant's relatively unknown “An Essay on the Maladies of the Mind” as well as his later discussion of the Seer of Swedenborg, that Kant formulates madness primarily in terms of sensory upheaval or other hallucinatory theaters. She writes: “madness is an organization of thought. It is made possible by the ambiguity of the normal relation between the imaginary and the perceived, whether this pertains to the order of sensation or to the relations between our ideas” Kant's fascination with the Seer forces Kant between the pincers of “aesthetic reconciliation” – namely melancholic withdrawal – and “a philosophical invention” – namely the critical project. Deleuze and Guattari's schizoanalysis is a combination and reversal of Kant's split, where an aesthetic over engagement with the world entails prolific conceptual invention. Their embrace of madness, however, is of course itself conceptual despite all their rhizomatic maneuvers. Though they move with the energy of madness, Deleuze and Guattari save the capacity of thought from the fangs of insanity by imbuing materiality itself with the capacity for thought. Or, as Ray Brassier puts it, “Deleuze insists, it is necessary to absolutize the immanence of this world in such a way as to dissolve the transcendent disjunction between things as we know them and as they are in themselves”. That is, whereas Kant relied on the faculty of judgment to divide representation from objectivity Deleuze attempts to flatten the whole economy beneath the juggernaut of ontological univocity. Speculation, as a particularly useful form of madness, might fall close to Deleuze and Guattari’s shaping of philosophy into a concept producing machine but is different in that it is potentially self destructive – less reliant on the stability of its own concepts and more adherent to exposing a particular horrifying swath of reality. Speculative madness is always a potential disaster in that it acknowledges little more than its own speculative power with the hope that the gibbering of at least a handful of hysterical brains will be useful. Pre-critical metaphysics amounts to madness, though this may be because the world itself is mad while new attempts at speculative metaphysics, at post-Kantian pre-critical metaphysics, are well aware of our own madness. Without the sobriety of the principle of sufficient reason we have a world of neon madness: “we would have to conceive what our life would be if all the movements of the earth, all the noises of the earth, all the smells, the tastes, all the light – of the earth and elsewhere, came to us in a moment, in an instant – like an atrocious screaming tumult of things”. Speculative thought may be participatory in the screaming tumult of the world or, worse yet, may produce its spectral double. Against theology or reason or simply commonsense, the speculative becomes heretical. Speculation, as the cognitive extension of the horrorific sublime should be met with melancholic detachment. Whereas Kant's theoretical invention, or productivity of thought, is self -sabotaging, since the advent of the critical project is a productivity of thought which then delimits the engine of thought at large either in dogmatic gestures or non-systematizable empirical wondrousness. The former is celebrated by the fiction of Thomas Ligotti whereas the latter is espoused by the tales of H.P. Lovecraft. /2/ – Weird Fiction and Philosophy. Supernatural horror, in all its eerie constructions, enables a reader to taste treats inconsistent with his personal welfare. Thomas Ligotti Songs of a Dead Dreamer. I choose weird stories because they suit my inclination best—one of my strongest and most persistent wishes being to achieve,momentarily, the illusion of some strange suspension or violation of the galling limitations of time, space, and natural law which forever imprison us and frustrate our curiosity about the infinite cosmic spaces beyond the radius of our sight and analysis H.P. Lovecraft. “Notes on Writing Weird Fiction” Lovecraft states that his creation of a story is to suspend natural law yet, at the same time, he indexes the tenuousness of such laws, suggesting the vast possibilities of the cosmic. The tension that Lovecraft sets up between his own fictions and the universe or nature is reproduced within his fictions in the common theme of the unreliable narrator; unreliable precisely because they are either mad or what they have witnessed questions the bounds of material reality. In “The Call of Cthulhu” Lovecraft writes: The most merciful thing in the world, I think, is the inability of the human mind to correlate all its contents. We live on a placid island of ignorance in the midst of black seas of infinity, and it was not meant that we should voyage far. The sciences, each straining in its own direction, have hitherto harmed us little; but some day the piecing together of dissociated knowledge will open up such terrifying vistas of reality, and of our frightful position therein, that we shall either go mad from the revelation or flee from the deadly light into the peace and safety of a new dark age. Despite Lovecraft's invocations of illusion, he is not claiming that his fantastic creations such as the Old Ones are supernatural but, following Joshi, are only ever supernormal. One can immediately see that instead of nullifying realism Lovecraft in fact opens up the real to an unbearable degree. In various letters and non-fictional statements Lovecraft espoused strictly materialist tenets, ones which he borrowed from Hugh Elliot namely the uniformity of law, the denial of teleology and the denial of non-material existence. Lovecraft seeks to explore the possibilities of such a universe by piling horror upon horror until the fragile brain which attempts to grasp it fractures. This may be why philosophy has largely ignored weird fiction – while Deleuze and Guattari mark the turn towards weird fiction and Lovecraft in particular, with the precursors to speculative realism as well as contemporary related thinkers have begun to view Lovecraft as making philosophical contributions. Lovecraft's own relation to philosophy is largely critical while celebrating Nietzsche and Schopenhauer. This relationship of Lovecraft to philosophy and philosophy to Lovecraft is coupled with Lovecraft's habit of mercilessly destroying the philosopher and the figure of the academic more generally in his work, a destruction which is both an epistemological destruction and an ontological destruction. Thomas Ligotti's weird fiction which he has designated as a kind of “confrontational escapism” might be best described in the following quote from one of his shortstories, “The human phenomenon is but the sum of densely coiled layers of illusion each of which winds itself on the supreme insanity. That there are persons of any kind when all there can be is mindless mirrors laughing and screaming as they parade about in an endless dream”. Whereas Lovecraft's weirdness draws predominantly from the abyssal depths of the uncharted universe, Ligotti's existential horror focuses on the awful proliferation of meaningless surfaces that is, the banal and every day function of representation. In an interview, Ligotti states: We don't even know what the world is like except through our sense organs, which are provably inadequate. It's no less the case with our brains. Our whole lives are motored along by forces we cannot know and perceptions that are faulty. We sometimes hear people say that they're not feeling themselves. Well, who or what do they feel like then? This is not to say that Ligotti sees nothing beneath the surface but that there is only darkness or blackness behind it, whether that surface is on the cosmological level or the personal. By addressing the implicit and explicit philosophical issues in Ligotti's work we will see that his nightmarish take on reality is a form of malevolent idealism, an idealism which is grounded in a real, albeit dark and obscure materiality. If Ligotti's horrors ultimately circle around mad perceptions which degrade the subject, it takes aim at the vast majority of the focus of continental philosophy. While Lovecraft's acidic materialism clearly assaults any romantic concept of being from the outside, Ligotti attacks consciousness from the inside: Just a little doubt slipped into the mind, a little trickle of suspicion in the bloodstream, and all those eyes of ours, one by one, open up to the world and see its horror [...] Not even the solar brilliance of a summer day will harbor you from horror. For horror eats the light and digests it into darkness. Clearly, the weird fiction of Lovecraft and Ligotti amount to a anti-anthrocentric onslaught against the ramparts of correlationist continental philosophy. /3/ – Shoggothic Materialism or the Formless Formless protoplasm able to mock and reflect all forms and organs and processes—viscous agglutinations of bubbling cells—rubbery fifteen-foot spheroids infinitely plastic and ductile—slaves of suggestion, builders of cities—more and more sullen, more and more intelligent, more and more amphibious, more and more imitative—Great God! What madness made even those blasphemous Old Ones willing to use and to carve such things? H.P. Lovecraft. “At the Mountains of Madness” On the other hand, affirming that the universe resembles nothing and is only formless amounts to saying that the universe is something like a spider or spit. Georges Bataille. “Formless”. The Shoggoths feature most prominently in H.P. Lovecraft's shortstory “At the Mountains of Madness” where they are described in the following manner: It was a terrible, indescribable thing vaster than any subway train – a shapeless congeries of protoplasmic bubbles, faintly self -luminous, and with myriads of temporary eyes forming and un-forming as pustules of greenish light all over the tunnel-filling front that bore down upon us, crushing the frantic penguins and slithering over the glistening floor that it and its kind had swept so evilly free of all litter. The term is a litmus test for materialism itself as the Shoggoth is an amorphous creature. The Shoggoths were living digging machines bio engineered by the Elder Things, and their protoplasmic bodies being formed into various tools by their hypnotic powers. The Shoggoths eventually became self aware and rose up against their masters in an ultimately failed rebellion. After the Elder Ones retreated into the oceans leaving the Shoggoths to roam the frozen wastes of the Antarctic. The onto-genesis of the Shoggoths and their gross materiality, index the horrifyingly deep time of the earth a concept near and dear to Lovecraft's formulation of horror as well as the fear of intelligences far beyond, and far before, the ascent of humankind on earth and elsewhere. The sickly amorphous nature of the Shoggoths invade materialism at large, where while materiality is unmistakably real ie not discursive, psychological, or otherwise overly subjectivist, it questions the relation of materialism to life. As Eugene Thacker writes: The Shoggoths or Elder Things do not even share the same reality with the human beings who encounter them—and yet this encounter takes place, though in a strange no-place that is neither quite that of the phenomenal world of the human subject or the noumenal world of an external reality. Amorphous yet definitively material beings are a constant in Lovecraft's tales. In his tale “The Dream-Quest of Unknown Kadatth” Lovecraft describes Azathoth as, “that shocking final peril which gibbers unmentionably outside the ordered universe,” that, “last amorphous blight of nethermost confusion which blashphemes and bubbles at the centre of all infinity,” who, “gnaws hungrily in inconceivable, unlighted chambers beyond time”. Azathoth's name may have multiple origins but the most striking is the alchemy term azoth which is both a cohesive agent and a acidic creation pointing back to the generative and the decayed. The indistinction of generation and degradation materially mirrors the blur between the natural and the unnatural as well as life and non-life. Lovecraft speaks of the tension between the natural and the unnatural is his short story “The Unnameable.” He writes, “if the psychic emanations of human creatures be grotesque distortions, what coherent representation could express or portray so gibbous and infamous a nebulousity as the spectre of a malign, chaotic perversion, itself a morbid blasphemy against Nature?”. Lovecraft explores exactly the tension outlined at the beginning of this chapter, between life and thought. At the end of his short tale Lovecraft compounds the problem as the unnameable is described as “a gelatin—a slime—yet it had shapes, a thousand shapes of horror beyond all memory”. Deleuze suggests that becoming-animal is operative throughout Lovecraft's work, where narrators feel themselves reeling at their becoming non-human or of being the anomalous or of becoming atomized. Following Eugene Thacker however, it may be far more accurate to say that Lovecraft's tales exhibit not a becoming-animal but a becoming-creature. Where the monstrous breaks the purportedly fixed laws of nature, the creature is far more ontologically ambiguous. The nameless thing is an altogether different horizon for thought. The creature is either less than animal or more than animal – its becoming is too strange for animal categories and indexes the slow march of thought towards the bizarre. This strangeness is, as aways, some indefinite swirling in the category of immanence and becoming. Bataille begins “The Labyrinth” with the assertion that being, to continue to be, is becoming. More becoming means more being hence the assertion that Bataille's barking dog is more than the sponge. This would mean that the Shoggotth is altogether too much being, too much material in the materialism. Bataille suggests that there is an immanence between the eater and the eaten, across the species and never within them. That is, despite the chaotic storm of immanence there must remain some capacity to distinguish the gradients of becoming without reliance upon, or at least total dependence upon, the powers of intellection to parse the universe into recognizable bits, properly digestible factoids. That is, if we undo Deleuze's aforementioned valorization of sense which, for his variation of materialism, performed the work of the transcendental, but refuse to reinstate Kant's transcendental disjunction between thing and appearance, then it must be a quality of becoming-as-being itself which can account for the discernible nature of things by sense. In an interview with Peter Gratton, Jane Bennett formulates the problem thusly: What is this strange systematicity proper to a world of Becoming? What, for example, initiates this congealing that will undo itself? Is it possible to identify phases within this formativity, plateaus of differentiation? If so, do the phases/plateaus follow a temporal sequence? Or, does the process of formation inside Becoming require us to theorize a non-chronological kind of time? I think that your student’s question: “How can we account for something like iterable structures in an assemblage theory?” is exactly the right question. Philosophy has erred too far on the side of the subject in the subject-object relation and has furthermore, lost the very weirdness of the non-human. Beyond this, the madness of thought need not override. /4/ - Ventriloquial Idealism or the Externality of Thought My aim is the opposite of Lovecraft's. He had an appreciation for natural scenery on earth and wanted to reach beyond the visible in the universe. I have no appreciation for natural scenery and want the objective universe to be a reflection of a character. Thomas Ligotti. “Devotees of Decay and Desolation.” Unless life is a dream, nothing makes sense. For as a reality, it is a rank failure [….] Horror is more real than we are. Thomas Ligotti. “Professor Nobody's Little Lectures on Supernatural Horror”. Thomas Ligotti's tales are rife with mannequins, puppets, and other brainless entities which of replace the valorized subject of philosophy – that of the free thinking human being. His tales such as “The Dream of the Manikin” aim to destroy the rootedness of consciousness. James Trafford has connected the anti-egoism of Ligotti to Thomas Metzinger – where the self is at best an illusion and we plead desperately for someone else to acknowledge that we are real. Trafford has stated it thus, “Life is played out as an inescapable puppet show, an endless dream in which the puppets are generally unaware that they are trapped within a mesmeric dance of whose mechanisms they know nothing and over which they have no control”. An absolute materialism, for Ligotti, implies an alienation of the idea which leads to a ventriloquil idealism. As Ligotti notes in an interview, “the fiasco and nightmare of existence, the particular fiasco and nightmare of human existence, the sense that people are puppets of powers they cannot comprehend, etc.” And then further elaborates that,“[a]ssuming that anything has to exist, my perfect world would be one in which everyone has experienced the annulment of his or her ego. That is, our consciousness of ourselves as unique individuals would entirely disappear”. The externality of the idea leads to the unfortunate consequence of consciousness eating at itself through horror which, for Ligotti, is more real than reality and goes beyond horror-as-affect. Beyond this, taking together with the unreality of life and the ventriloquizing of subjectivity, Ligotti's thought becomes an idealism in which thought itself is alien and ultimately horrifying. The role of human thought and the relation of non-relation of horror to thought is not completely clear in Ligotti's The Conspiracy Against the Human Race. Ligotti argues in his The Conspiracy Against the Human Race,that the advent of thought is a mistake of nature and that horror is being in the sense that horror results from knowing too much. Yet, at the same time, Ligotti seems to suggest that thought separates us from nature whereas, for Lovecraft, thought is far less privileged – mind is just another manifestation of the vital principal, it is just another materialization of energy. In his brilliant “Prospects for Post-Copernican Dogmatism” Iain Grant rallies against the negative definition of dogmatism and the transcendental, and suggests that negatively defining both over-focuses on conditions of access and subjectivism at the expense of the real or nature. With Schelling, who is Grant's champion against the subjectivist bastions of both Fichte and Kant, Ligotti's idealism could be taken as a transcendental realism following from an ontological realism. Yet the transcendental status of Ligotti's thought move towards a treatment of the transcendental which may threaten to leave beyond its realist ground. Ligotti states: Belief in the supernatural is only superstition. That said, a sense of the supernatural, as Conrad evidenced in Heart of Darkness, must be admitted if one's inclination is to go to the limits of horror. It is the sense of what should not be- the sense of being ravaged by the impossible. Phenomenally speaking, the super-natural may be regarded as the metaphysical counterpart of insanity, a transcendental correlative of a mind that has been driven mad. Again, Ligotti equates madness with thought, qualifying both as supernatural while remaining less emphatic about the metaphysical dimensions of horror. The question becomes one of how exactly the hallucinatory realm of the ideal relates to the black churning matter of Lovecraft's chaos of elementary particles. In his tale “I Have a Special Plan for This World” Ligotti formulates thus: A: There is no grand scheme of things. B: If there were a grand scheme of things, the fact – the fact – that we are not equipped to perceive it, either by natural or supernatural means, is a nightmarish obscenity. C: The very notion of a grand scheme of things is a nightmarish obscenity. Here Ligotti is not discounting metaphysics but implying that if it does exist the fact that we are phenomenologically ill-equipped to perceive that it is nightmarish. For Ligotti, nightmare and horror occur within the circuit of consciousness whereas for Lovecraft the relation between reality and mind is less productive on the side of mind. It is easier to ascertain how the Kantian philosophy is a defense against the diseases of the head as Kant armors his critical enterprise from too much of the world and too much of the mind. The weird fiction of both Lovecraft and Ligotti demonstrates that there is too much of both feeding into one another in a way that corrodes the Kantian schema throughly, breaking it down into a dead but still ontologically potentiated nigredo. The haunting, terrifying fact of Ligotti's idealism is that the transcendental motion which brought thought to matter, while throughly material and naturalized, brings with it the horror that thought cannot be undone without ending the material that bears it either locally or completely. Thought comes from an elsewhere and an elsewhen being-in-thought. The unthinkable outside thought is as maddening as the unthought engine of thought itself within thought which doesn't exist except for the mind, the rotting décor of the brain. /5/ - Hyperstitional Transcendental Paranoia or Self -Expelled Thought Weird fiction has been given some direct treatment in philosophy in the mad black Deleuzianism of Nick Land. Nick Land along with others in the 1990s created the Cyber Culture Research Unit as well as the research group Hyperstition. The now defunct hyperstitional website, an outgrowth of the Cyber Culture Research Unit, defined hyperstition in the following fourfold: 1-Element of effective culture that makes itself real. 2-Fictional quantity functional as a time-traveling device. 3-Coincidence intensifier. 4-Call to the Old Ones. The distinctively Lovecraftian character of hyperstition is hard to miss as is its Deleuzo-Guattarian roots. In the opening pages of A Thousand Plateaus Deleuze and Guattari write, “We have been criticized for over-quoting literary authors. But when one writes, the only question is which other machine the literary machine can be plugged into”. The indisinction of literature and philosophy mirrors the mess of being and knowing as post-correlationist philosophy, where philosophy tries to make itself real where literature, especially the weird, aims itself at the brain-circuit of horror. The texts of both Lovecraft and Ligotti work through horror as epistemological plasticity meeting with proximity as well as the deep time of Lovecraft and the glacially slow time of paranoia in Ligotti. Against Deleuze, and following Brassier, we cannot allow the time of consciousness, the Bergsonian time of the duree, to override natural time, but instead acknowledge that it is an unfortunate fact of existence as a thinking being. Horror-time, the time of consciousness, with all its punctuated moments and drawn out terrors, cannot compare to the deep time of non-existence both in the unreachable past and the unknown future. The crystalline cogs of Kant's account of experience as the leading light for the possibility of metaphysics must be throughly obliterated. His gloss of experience in Prolegomena to any Future Metaphysics could not be more sterile: Experience consists of intuitions, which belong to the sensibility, and of judgments, which are entirely a work of the understanding. But the judgments which the understanding makes entirely out of sensuous intuitions are far from being judgments of experience. For in the one case the judgment connects only the perceptions as they are given in sensuous intuition [....] Experience consists in the synthetic connection of appearances in consciousness, so far as this connection is necessary. Here it is difficult to dismiss the queasiness that Kant's legalism induces upon sight for both Badiou and David-Menard. Kant's thought becomes, as Foucault says when reflecting on Sade's text in relation to nature, “the savage abolition of itself”. For Badiou, Kant's philosophy simply closes off too much of the outside, freezing the world of thought in an all too limited formalism. Critical philosophy is simply the systematized quarantine on future thinking, on thinking which would threaten the formalism which artificially grants thought its own coherency in the face of madness. Even the becoming-mad of Deleuze, while escaping the rumbling ground, makes grounds for itself, mad grounds but grounds which are thinkable in their affect. The field of effects allows for Deleuze's aesthetic and radical empiricism, in which effects and/or occasions make up the material of the world to be thought as a chaosmosis of simulacra. Given a critique of an empiricism of aesthetics, of the image, it may be difficult to justify an attack on Kantian formalism with the madness of literature, which does not aim to make itself real but which we may attempt to make real. That is, how do Lovecraft's and Ligotti's materials, as materials for philosophy to work on, differ from either the operative formalisms of Kant or the implicitly formalized images of Deleuzian empiricism? It is simply that such texts do not aim to make themselves real, and make claims to the real which are more alien to us than familiar, which is why their horror is immediately more trustworthy. This is the madness which Blanchot discusses in The Infinite Conversation through Cervantes and his knight – the madness of book-life, of the perverse unity of literature and life a discussion which culminates in the discussion of one of the weird's masters, that of Kafka. The text is the knowing of madness, since madness, in its moment of becoming-more-mad, cannot be frozen in place but by the solidifications of externalizing production. This is why Foucault ends his famous study with works of art. Furthermore extilligence, the ability to export the products of our maligned brains, is the companion of the attempts to export, or discover the possibility of intelligences outside of our heads, in order for philosophy to survive the solar catastrophe. To borrow again from Deleuze, writing is inseparable from becoming. The mistake is to believe that madness is reabsorbed by extilligence, by great works, or that it could be exorcised by the expelling of thought into the inorganic or differently organic. Going out of our heads does not guarantee we will no longer mean we cannot still go out of our minds. This is simply because of the outside, of matter, or force, or energy, or thing-in-itself, or Schopenhauerian Will. In Lovecraft’s “The Music of Erich Zahn” an “impoverished student of metaphysics” becomes intrigued by strange viol music coming from above his room. After meeting the musician the student discovers that each night he plays frantic music at a window in order to keep some horridness at bay, some “impenetrable darkness with chaos and pandemonium”. The aesthetic defenses provided by the well trained brain can bear the hex of matter for so long, the specter of unalterability within it which too many minds obliterate, collapsing everything before the thought of thought as thinkable or at least noetically mutable on our own terms. Transcendental paranoia is the concurrent nightmare and promise of Paul Humphrey's work, of being literally out of our minds. It is the gothic counterpart of thinking non-conceptually but also of thinking never belonging to any instance of purportedly solid being. As Bataille stated, “At the boundary of that which escapes cohesion, he who reflects within cohesion realizes there is no longer any room for him” Thought is immaterial only to the degree that it is inhuman, it is a power that tries, always with failure, to ascertain its own genesis. Philosophy, if it can truly return to the great outdoors, if it can leave behind the dead loop of the human skull, must recognize not only the non-priority of human thought, but that thought never belongs to the brain that thinks it, thought comes from somewhere else. To return to the train image from the beginning “a locomotive rolling on the surface of the earth is the image of continuous metamorphosis” this is the problem of thought, and of thinking thought, of being no longer able to isolate thought, with only a thought-formed structure. [1] One of the central tenets of Francois Laruelle's non-philosophy is that philosophy has traditionally operated on material already presupposed as thinkable instead of trying to think the real in itself. Philosophy, according to Laruelle, remains fixated on transcendental synthesis which shatters immanence into an empirical datum and an a prori factum which are then fused by a third thing such as the ego. For a critical account of Laruelle's non-philosophy see Ray Brassier's Nihil Unbound. (shrink)

OBJETIVO A gestação nos mamíferos domésticos é um processo fisiológico que implica mudanças físicas, metabólicas e hormonais na fêmea, que culminam com o nascimento de um novo indivíduo. Desta forma, a compreensão de tais mudanças e como estas favorecem um ambiente ideal de desenvolvimento embrionário inicial, até a placentação e a fisiologia envolvidas durante esses processos é fundamental na tomada de decisões quanto à saúde reprodutiva da fêmea, na seleção de futuras matrizes e até mesmo para a saúde fetal e (...) sanidade do novo animal. Neste capítulo, o estudante compreenderá de forma clara, concisa, didática e objetiva, as adaptações maternas e fetais para o estabelecimento da gestação após a fecundação, o desenvolvimento desta e também identificará as diferenças existentes entre as espécies de interesse zootécnico. INTRODUÇÃO O estabelecimento da gestação nos mamíferos domésticos inclui três etapas fundamentais: o reconhecimento materno da gestação ou prenhez (RMP), a implantação e a placentação. Dentro da fisiologia da reprodução nos mamíferos, a implantação e a placenta- ção constituem processos essenciais na nutrição do embrião e do feto e, portanto, para seu desenvolvimento; devido a isso, são etapas críticas para a produção animal já que possuem um efeito direto sobre a eficiência reprodutiva. Nos bovinos leiteiros, por exemplo, estima-se uma taxa de fertilização perto de 95%, embora apenas 55% desses zigotos se desenvolvam e cheguem ao parto, o qual representa uma perda de gestações perto de 35%. Entre 70% e 80% das mortes embrionárias ocorrem durante as três semanas seguintes à ovulação, o que coincide com o período no qual se estabelecem os processos de implantação e placentação supracitados. O desenvolvimento embrionário precoce depende da sincronia de eventos entre o oviduto-útero e o embrião. Foi determinado que a presença do embrião pode modificar as secreções ovidutais e uterinas durante as fases iniciais de desenvolvimento. O ambiente endócrino materno (predominância de progesterona) também modula as características das secreções ovidutais e uterinas para assegurar a sobrevivência embrionária no caso da fertilização ter sido bem sucedida. Se este último ocorrer, então o embrião deverá indicar à mãe a sua existência para que sejam mantidas as condições adequadas ao seu desenvolvimento. Como supracitado, o embrião em seu curso pelo oviduto requer certas secreções para sobreviver e desenvolver-se, no entanto, graças à fertilização in vitro, têm-se dispensado a importância das secreções ovidutais, já que se observou que um embrião é capaz de se desenvolver em condições laboratoriais fora do aparelho reprodutor materno durante as suas fases iniciais, e consegue estabelecer uma gestação normal que chega a termo após a sua reintrodução no útero. Em estágios mais tardios de desenvolvimento o embrião necessita necessariamente do meio uterino para sobreviver e continuar o seu crescimento. No bovino, por exemplo, o embrião só é capaz de alongar-se estando dentro do útero, indicando a presença de fatores específicos necessários para que o embrião se desenvolva de maneira normal. Um meio endócrino no qual predomina a progesterona materna durante a gestação induz a secreção do histiotrofo (ou leite uterino) que permite a nutrição e a sobrevivência do embrião antes da implantação e da formação da placenta, através do qual obterá a maioria do fornecimento e intercâmbio necessários para continuar o seu desenvolvimento intra-uterino. SEGMENTAÇÃO E DESENVOLVIMENTO EMBRIONÁRIO PRECOCE O desenvolvimento embrionário precoce, conhecido como período de pré- -implantação, é essencial; inclui processos de divisão e diferenciação celular que são realizadas no início com uma elevada sincronização para garantir o desenvolvimento correto do indivíduo dentro do útero. Esta fase envolve a passagem do zigoto (unicelular), a embrião (multicelular) e, por fim, em concepto (quando se distingue o embrião com suas membranas extraembrionárias). O desenvolvimento precoce é o estágio mais dinâmico e vulnerável na formação de um indivíduo. Investigações recentes demonstraram que alterações nesta etapa podem modificar características produtivas ou reprodutivas durante a vida adulta. É por isso que é necessário conhecer as etapas fisiologicamente normais envolvidas neste processo (figura 1). Em fases mais tardias de desenvolvimento, o embrião se converterá em um feto com todos os sistemas e tecidos diferenciados observados num animal adulto. Após a fertilização, o zigoto resultante é capaz de dar origem a um novo organismo completo, de modo que se considera como uma célula totipotencial. O desenvolvimento embrionário começa e se consegue graças a uma série de divisões mitóticas conhecidas como segmentação ou clivagem (cleavage, em inglês). A primeira divisão mitótica dá origem a duas células filhas idênticas (figura 1), e ocorre por volta das 20 às 30 horas depois da fertilização, com divisões subsequentes a cada 12 a 24 h, dependendo da espécie. As células resultantes destas divisões são conhecidas como blastômeros. A orientação da divisão inicial que dá origem aos dois primeiros blastô- meros, parece ser guiada pela posição dos corpos polares. As divisões iniciais das células embrionárias são sincrônicas, no entanto, conforme o desenvolvimento se torna assincrônicas. Assim, a divisão mitótica inicial dá origem a um embrião de duas células (dois blastômeros), a segunda a um embrião de quatro células, a terceira a um de oito células e a quarta a um com 16 células, onde passa a ser chamado de mórula. Estas divisões são realizadas sem o aumento do volume do citoplasma, para que seja restabelecida uma proporção celular mais adequada à das células somáticas, já que o ovócito é a célula mais grande do organismo (um ovócito mede entre 100 e 150 μm do ovócito, enquanto uma célula somática mede de 10 a 20 μm); e porque o embrião ainda está contido dentro da zona pelúcida (figura 1). Um dos pontos críticos durante o desenvolvimento embrionário precoce é a ativação do genoma embrionário. Durante as etapas iniciais após a fertilização, as proteínas e RNAs “herdados” do ovócito são responsáveis pelo metabolismo e desenvolvimento inicial do embrião. É apenas até o estágio de quatro (ratos) ou oito blastômeros (espécies domésticas e humanas) em que o embrião começa a sintetizar o seu próprio RNAm (mensageiro) e as proteínas específicas necessárias para controlar o seu crescimento e metabolismo. A qualidade do ovócito que é fertilizado, consequente- mente, tem um grande impacto sobre a sobrevivência inicial do embrião. Quando o embrião atinge uma média de 16 a 32 células é conhecido como mórula (tabela 1) (do latim morus: mora), e nesta fase o embrião começa a compactar-se, o que ocorre porque começam a estabelecer-se diferentes uniões celulares, de acordo com a relação espacial entre os blastômeros. As células centrais desenvolvem-se incluindo entre elas junções comunicantes, conhecidas também como junções GAP, enquanto as que se encontram na periferia estabelecem uniões estreitas, dando origem a duas subpopulações distintas de blastômeros: periféricos e centrais. Cabe mencionar que os blastômeros que compõem a mórula ainda são células capazes de dar origem a um novo indivíduo completo, ou seja, são totipotenciais. À medida que a mórula continua a dividir-se e a crescer, as células localizadas na periferia começam a liberar sódio para os espaços intercelulares, criando uma diferença na pressão osmótica seguida pela entrada de água ao embrião. O líquido se acumula e provoca a separação das células, distinguindo ainda mais as duas subpopulações de células mencionadas (periféricas e centrais) e forma-se uma cavidade cheia de líquido. Esta cavidade é conhecida como blastocele; com a sua formação o embrião entra em fase de blastocisto (figura 1, tabela 1). Da subpopulação celular da periferia se origina do trofoblasto (trofoectoderma) que formará a maioria das membranas extraembrionárias (placenta), e da subpopulação central é estabelecida a massa celular interna ou embrioblasto, que dará origem ao embrião propriamente dito, ou seja, ao feto. Ao continuar a multiplicação e crescimento do trofoblasto à medida que o blastocisto se desenvolve, as células da massa interna se diferenciam novamente em dois segmentos distintos: a endoderme primitiva ou hipoblasto e o epiblasto (figura 1), em que todos os tecidos do organismo (saco vitelino) são originados e as células germinativas primordiais. Uma vez formado, o epiblasto continua a dividir-se e a diferenciar-se para dar origem às três placas ou camadas germinativas conhecidas como endoderme, mesoderme e ectoderme. Este processo é conhecido como gastrulação, e durante este diferem-se no embrião as porções craniais, caudais, dorsais e ventrais, processo conhecido como polaridade do embrião, que orienta o desenvolvimento dos diversos tecidos e órgãos do indivíduo. À medida que o blastocisto continua crescendo e diferenciando-se, vai-se acumulando mais líquido no blastocele, com o que a pressão interna aumenta e a zona pelúcida começa a ficar mais fina. Este fato, juntamente com a ação de proteases produzidas pelo embrião, leva à ruptura da zona pelúcida e à saída do blastocisto (eclosão), pelo que, uma vez liberado, o embrião é conhecido como blastocisto eclodido. O trofoblasto embrionário entra, então, em contato direto com o endométrio, o que é considerado como o início da implantação. IMPLANTAÇÃO O trofoblasto embrionário, também conhecido como trofoectoderma, dá origem à maioria das membranas fetais ou placenta fetal. O processo no qual o trofoblasto se une ao endométrio materno é conhecido como implantação; para isso ocorre uma série de processos altamente sincronizados envolvendo secreções embrionárias e maternas, e interações físicas, durante um período limitado conhecido como janela de receptividade. A implantação é considerada um processo gradual que genericamente se divide em cinco fases, algumas das quais podem sobrepor-se parcialmente e diferir segundo a espécie: 1. Eclosão do blastocisto da zona pelúcida (figura 2); -/- 2. Pré-contato e orientação do blastocisto. É o contato inicial entre as células do trofoblasto e do epitélio endometrial, bem como a orientação da massa celular interna e do trofoectoderma, que assume especial importância em espécies cuja implantação é invasiva, como em roedores e primatas; 3. Aposição - refere-se ao posicionamento do blastocisto numa determinada área e de uma forma específica no útero. Começa a interdigitação das vilosidades coriônicas com o epitélio luminal do endométrio. 4. Adesão - requer sistemas de sinalização que envolvem glicoproteínas de adesão, como integrinas, selectinas e galectinas, com os seus ligantes, tanto no epitélio luminal como no epitélio trofoectoderma. 5. Invasão endometrial - este termo se relaciona ao tipo de placentação e é pertinente sobretudo para aquelas espécies onde existe uma fusão entre células do trofoblasto e do epitélio do endométrio durante a formação da placenta, ou que as células trofoblásticas penetrem as camadas endometriais e até modifiquem as células do endométrio que as rodeiam. Existem três tipos de implantação ou nidação. Na nidação central ou não invasiva, a vesícula embrionária ocupa uma posição central na luz do útero e, na sua relação com a mucosa uterina, unicamente através das vilosidades coriônicas (projeções das células trofoblásticas dentro das quais crescem capilares do feto), há adesão mas não invasão da mucosa. Este tipo ocorre nos ungulados domésticos, mas não em carnívoros. Na nidação excêntrica a vesícula embrionária está inserida num canal profundo da mucosa, parcialmente isolada da luz principal, e se apresenta na rata, cadela e gata. A nidação intersticial é própria dos primatas, rato e cobaia, e nesta produz-se a destruição do epitélio e do tecido conjuntivo do útero, de modo que a vesícula embrionária se afunda na própria lâmina mucosa e se desenvolve em um espaço intersticial. Até o momento da implantação, a nutrição do embrião é histotrófica, sendo as substâncias necessárias absorvidas através do trofoblasto, como foi mencionado anteriormente. A partir deste momento, o trofoblasto começa o desenvolvimento de uma série de membranas extraembrionárias que permitirão finalmente a troca de nutrientes e metabólitos entre o sangue materno e o do embrião, constituindo a placenta. Um fato necessário na implantação é a perda de receptores para progesterona no epitélio luminal do endométrio, e pré-sensibilização do mesmo pelos estrógenos. Apesar de parecer um efeito contraditório, este requisito permite o desaparecimento de uma camada de mucina e outros compostos proteicos, que revestem o endométrio e que atuam como uma película antiaderente que inicialmente não permite a aposição e adesão do embrião. O desaparecimento desta camada ocorre durante a janela de receptividade, seja em toda a superfície do endométrio (ruminantes, suínos e roedores) ou nas zonas específicas onde o blastocisto será implantado (humano e coelho). Por esta razão, a interação física entre o embrião e o endométrio desempenha um papel importante na implantação. Uma vez que a camada de glicoproteínas desaparecer, é possível a aposição do trofoectoderma embrionário e das células epiteliais do endométrio, iniciando assim a implantação propriamente dita através da intercomunicação entre os dois tecidos. A implantação pode ser considerada como a fixação do embrião ao útero a partir do ponto de vista físico e funcional. No entanto, como se trata de um processo progressivo e gradual, em que algumas das suas fases podem ser parcialmente sobrepostas, não existe consenso sobre o período em que se inicia e termina. Na borrega, por exemplo, estima-se que ocorra entre o dia 10 e o dia 22, enquanto na vaca entre os dias 11 e 40 pós-ovulação. Nas espécies polítocas, isto é, fêmeas que parem várias crias como as porcas, os blastocistos se distribuem ao longo dos cornos uterinos como resultado de movimentos musculares da parede uterina, aparentemente regulados por prostaglandinas e outros fatores secretados pelo útero. Por exemplo, nas porcas, os blastocistos se movem livremente entre os cornos, e a distribuição dos embriões ao implantar-se é mais uniforme do que poderia ser esperado se ocorresse meramente ao acaso. Tem observado que a deficiência na produção de ácido lisofosfatídico 3 (LPA3) e/ou seu receptor, ocasiona uma falha na distribuição dos embriões no útero. Por outro lado, não há evidência de que um blastocisto implantado exerça alguma influência inibitória sobre a implantação de outro blastocisto próximo a ele. Como supracitado, o processo de implantação inclui uma complexa interação entre o embrião e o útero, e cada um deles provê de estímulos essenciais para favorecer a progressão do outro, apresentando-se diferenças em tempos e particularidades dentro das diferentes espécies. -/- Porca O período de adesão situa-se entre os dias 12 e 24 após a fertilização. Ao redor do dia sete, o blastocisto é eclodido, porque o trofoblasto está em contato direto com o epitélio uterino e começa a proliferar com rapidez. O endoderme se forma e o blastocisto muda de uma pequena vesícula esférica para um tubo muito alongado que chega a medir cerca de um metro em poucos dias, ele que lhe proporciona uma superfície muito ampla para a absorção de nutrientes. Cadela Os embriões migram entre os dois cornos uterinos do dia 12 ao 17 após a fertilização, distribuindo-se de maneira uniforme. Estes embriões aderem ao endométrio entre os dias 16 e 18, e alcançam sua implantação final entre o dia 17 e 20 da gestação. Cabe ressaltar que nos caninos o período de pré-implantação é o mais longo das espécies domésticas, o que ocorre porque a cadela ovula ovócitos imaturos (ovócitos primários) que precisam amadurecer por dois a três dias, para formar ovócitos secundários, antes que a fertilização seja possível. Por isso, o zigoto canino chega à junção útero-tubárica entre o sétimo e o décimo dia após o pico pré-ovulatório de LH (a ovulação ocorre, em média, dois dias após o pico de LH), entrando no útero em estágio de mórula ou blastocisto em torno dos dias 10 a 12 depois do referido pico. Ovelha O desenvolvimento precoce do blastocisto é muito semelhante ao da porca. Observa-se certo grau de adesão desde o dia 10 da gestação, mas o alongamento do embrião é menos extenso do que em suínos e tem início entre o dia 11 e 12. Para a terceira semana o embrião ovino chega a medir até 30 cm de comprimento. O processo de implantação é concluído aproximadamente entre a quarta e quinta semana de gestação (figura 3). Vaca O processo de implantação é semelhante ao da borrega, mas tem início mais tarde. A zona pelúcida se perde por volta do dia 9 a 10 (blastocisto eclodido) e o embrião começa a alongar-se ao redor do dia 12 a 14, atingindo um comprimento de cerca de 60 mm para o dia 16, embora possa haver uma grande variação individual. A partir do dia 33, o córion é formado e existe uma adesão inicial que inclui dois ou quatro cotilédones, que se interdigitam rapidamente com o tecido materno de modo que o embrião começa a nutrir-se através deles. Égua O blastocisto atinge um diâmetro de cinco centímetros aos dois meses e pratica- mente não se alonga. Entre os dias seis e sete após a ovulação, o embrião começa a revestir-se de uma camada glicoproteica que se forma entre o trofoectoderma e a zona pelúcida e que contém e mantém o embrião esférico depois de ter eclodido. Esta cápsula é uma estrutura única nos equinos (cápsula embrionária), afina-se no dia 18 e se perde entre os dias 21 e 23 de gestação. Na décima semana as microvilosidades do córion se interdigitam com a mucosa da parede uterina e na semana 14 é completada a implantação. Espécies não domésticas Em algumas espécies como os marsupiais, os ursos, focas, doninhas e alguns tipos de cervídeos, pode interromper-se temporariamente o desenvolvimento do embrião in utero e adiar a sua implantação, como estratégia evolutiva para favorecer o nascimento das crias em condições ambientais favoráveis para a sua sobrevivência. Esta estratégia é conhecida como diapausa e pode ser uma condição obrigatória ou facultativa para cada gestação, dependendo da espécie. Os mecanismos que a desencadeiam e a concluem não estão totalmente explicados e são espécie-específica. RECONHECIMENTO MATERNO DA GESTAÇÃO (RMG/RMP) O estabelecimento da gestação em mamíferos domésticos requer a presença de um corpo lúteo CL funcional que produz progesterona em quantidades adequadas para manter o desenvolvimento embrionário inicial e permitir mudanças necessárias durante o período de peri-implantação. Para que o corpo lúteo seja mantido e a fêmea seja impedida de reiniciar um novo ciclo estral, o embrião deve sinalizar sua presença para a mãe. O sinal para o reconhecimento materno da gestação (RMG) provém então do embrião e podem ser de dois tipos: luteotrópico ou anti-luteolítico. No primeiro, a(s) substância(s) produzida(s) pelo embrião que atua(am) sobre o corpo lúteo para manter sua funcionalidade, por exemplo a gonadotrofina coriônica humana (hCG) e a prolactina em roedores. O segundo tipo de sinal previne ativamente a luteólise, e é o mecanismo presente nas espécies domésticas em que o embrião produz substâncias como o interferon-τ (IFN-τ) em ruminantes ou os estrógenos em suínos. Ruminantes Como supracitado, o IFN-τ é responsável pela sinalização para o reconhecimen- to materno da gestação neste grupo que engloba cabras, ovelhas e vacas (figura 4). É um fator produzido pelas células do trofoblasto do embrião, e pode ser detectado a partir dos dias 11 a 12 em ovinos e de 14 a 15 em bovinos. Uma vez secretado, o IFN-τ impede a lise do corpo lúteo (efeito anti-luteolítico) por meio do bloqueio indireto da síntese de prostaglandina F2 alfa (PGF2α). No trabalho acerca do ciclo estral foi explicado que a luteólise requer a presença de receptores de ocitocina (OTR) no endométrio, que ao unir-se ao seu ligante, a ocitocina (proveniente inicialmente do hipotálamo e posteriormente de origem lútea), estimulam a produção de PGF2α e estabelecem um feedback positivo, que culminará na destruição do CL. Para que os OTRs sejam sintetizados, é necessária uma estimulação prévia do endométrio com estradiol, que ocorre através da ligação com seus receptores (ER-1). O mecanismo pelo qual o IFN-τ impede a lise do corpo lúteo é bloqueando, direta ou indiretamente, a síntese de OTR e, consequentemente, a produção pulsátil de PGF2α. Suínos No caso dos suínos, considera-se que o sinal embrionário para o reconhecimento materno da gestação são os estrógenos, produzidos pelos embriões em torno do dia 11 a 12 pós-ovulação. O endométrio suíno produz PGF2α que, quando não há gestação, é secretado na circulação uterina (secreção endócrina), de onde é transportada em direção ao CL para causar luteólise. Se há embriões no útero produzindo suficiente quantidades de estradiol, isso redireciona a secreção de PGF2α para o lúmen uterino (secreção exócrina), evitando que seja liberado para a circulação e, portanto, é sequestrado impedindo que chegue ao corpo lúteo (figura 5). É importante enfatizar que a produção de PGF2α não é inibida, mas sua secreção é redirecionada. Este mecanismo é conhecido como teoria endócrino-exócrina. Vale ressaltar que para o sinal de reconhecimento materno da gestação na porca ser eficiente, é necessário a presença de pelo menos quatro embriões, dois em cada corno, uma vez que se não houver dois embriões, um em cada corno, ocorre luteólise e reinicia a atividade cíclica. Embora os estrógenos sejam identificados como o sinal de reconhecimento materno nesta espécie, o embrião suíno também produz outros fatores, como a PGE2 e o ácido lisofosfatídico, considerado necessário para o estabelecimento adequado da gestação. A PGE2 ocasiona uma redução na produção de PGF2α em favor da PGE2 no endométrio e favorece a contração do miométrio para permitir a migração de embriões. O ácido lisofosfatídico, juntamente com seu receptor, é um fator crítico que favorece a migração intra-uterina, e permite uma distribuição adequada dos embriões ao longo dos cornos. Outras substâncias produzidas pelo embrião suíno são o IFN-delta (IFN-δ) e IFN-gama (IFN-γ), que não possuem ação anti-luteolítica, mas poderiam intervir no processo de implantação. Equinos Na égua é essencial que o embrião, ainda rodeado pela sua cápsula embrionária, migre de 12 a 14 vezes por dia através do útero, entre os dias 12 e 14 após ovulação, a fim de distribuir o fator de reconhecimento materno (figura 6). Embora seja sabido que existe, este último ainda não foi identificado, mas foi estabelecido que é da natureza proteica e seu principal efeito é a inibição da produção endometrial de PGF₂α, mediante a redução na formação do receptores de ocitocina; desta forma, evita-se o início do sinal luteolítico. É interessante notar que nesta espécie a ocitocina não é de origem lútea e sim endometrial. Primatas Ao contrário das espécies domésticas mencionadas, o mecanismo de ação do sinal de reconhecimento materno em primatas é luteotrópico. No humano, o embrião produz gonadotrofina coriônica humana (hCG) após o início da implantação (dias 6 a 8). A hCG estende a vida funcional do CL por meio de sua ligação a receptores lúteos para LH, estimulando assim a liberação de progesterona. Este efeito permite a “sobrevivência” do CL pelo menos até o momento em que a produção de progesterona é transferida para a placenta para levar a gestação a termo. Carnívoros Na cadela não é necessário o reconhecimento da gestação, já que normalmente o corpo lúteo tem uma vida média maior que a duração da gestação. Como na égua, a migração dos embriões através do útero antes da implantação pode favorecer o reconhecimento materno. Adicionalmente, tem sido descrito que durante o período antes da implantação (< 10 dias depois da ovulação), há um aumento na expressão de genes relacionados com a imunomodulação local (IFN-γ, IL-4 e CD8+), que não estão presentes em cadelas durante o diestro. A produção de IFN-γ por parte do embrião canino, como em outras espécies, pode estar envolvida na implantação ou o reconheci- mento da gestação, mas até o momento não foi demonstrado de forma inequívoca. Na gata doméstica, o fator que favorece o reconhecimento materno da gestação ainda não foi descrito. Temos que lembrar que seja qual for o mecanismo envolvido, a produção do sinal embrionário de reconhecimento materno da gestação é importante, já que a contínua presença de progesterona na circulação materna, faz possível que ocorra o desenvolvimento precoce do embrião e eventualmente a implantação, com a formação do órgão temporal mais importante para o desenvolvimento fetal: a placenta. Resumindo, o sinal enviado pelo embrião deve ser dado antes do útero começar a secretar PGF2a, hormônio que causa a destruição do corpo lúteo produtor da progesterona necessária para a gestação. O embrião deve secretar algumas substâncias (denominadas EPF: Early Pregnant Factors/fatores de gestação precoce) que capte o endométrio materno e sirva para evitar a ação luteolítica da PGF2a. Na porca, em vez de ser evitada a secreção de PGF2a, o referido hormônio é “sequestrado na luz do útero” e, desta forma, passa a secretar-se em forma exócrina, sem ter efeito sobre o corpo lúteo. No bovino, o reconhecimento materno da gestação é o processo fisiológico no qual o embrião, por meio de sinais moleculares como a secreção de interferon-τ (IFN-τ), anuncia sua presença no trato reprodutivo materno a fim de evitar que seja desencadeado o mecanismo luteolítico exercido pela PGF2a sobre o corpo lúteo. PLACENTAÇÃO Nos mamíferos domésticos, o processo de implantação é gradual e prolongado, e ocorre paralelamente a processos como a gastrulação e a formação de membranas extra- embrionárias: saco vitelino, âmnio, alantóides e córion. A formação das membranas extraembrionárias nos mamíferos eutérios, ou seja, aqueles que formam uma placenta completa, é um processo indispensável que permite ao embrião aderir-se ou implantar-se ao endométrio materno. As quatro membranas extraembrionárias mencionadas são formadas a partir do trofoblasto, mesoderme e endoderme embrionários. O saco vitelino fornece nutrientes no desenvolvimento inicial do embrião e se converte em vestigial quando a gestação progride; tem origem no endoderma primitivo, estrutura que junta com o trofoblasto e o mesoderma, formam o córion e âmnions. O âmnion contém o líquido amniótico que está em contato direto com o embrião e é a membrana mais interna; ademais, protege o feto, proporciona lubrificação para o parto e serve como um depósito para urina e resíduos fetais. O córion, por outro lado, é a membrana mais externa do embrião e, portanto, é a que entra em contato direto com o endométrio uterino materno; se fixa ao útero, absorve nutrientes do útero, permite a troca gasosa materno/fetal e produz hormônios. O alantóide se origina de uma evaginação do intestino primitivo e é de onde surge o sistema vascular da placenta fetal; a fusão com o córion (placenta cotiledonária), carrega os vasos sanguíneos do cordão umbilical, que liga o feto com o alantóide e é um reservatório de nutrientes e resíduos. Conforme o embrião se desenvolve, o saco vitelino regride e o alantóide se enche de líquido, pelo que este último se funde com o córion para formar o corioalantóides, que se torna a membrana mais externa e, portanto, a porção fetal do placenta. A placenta é um órgão temporário que representa uma interface através da qual realiza a troca bidirecional de nutrientes, gases, hormônios e outras substâncias entre a mãe e o feto. A unidade funcional da placenta são as vilosidades corioalantóicas, as quais são projeções pequenas dos corioalantóides que se interdigitam com o endométrio uterino, cuja superfície de absorção permite essa troca. A placenta é um órgão endócrino capaz de produzir uma gama de hormônios que ajudam a controlar o ambiente uterino, favorecendo o desenvolvimento do feto, além disso possui um papel importante no momento do parto. Nas diferentes espécies a placenta tem características particulares, pelo qual existem várias classificações, de acordo com a sua posição uterina, a distribuição das vilosidades corioalantóicas e a sua histologia. Posição uterina Refere-se à posição do concepto em relação ao lúmen uterino (figura 7). Central: O concepto ao ser implantado permanece em contato com o lúmen do útero. A maioria das espécies domésticas de importância veterinária estão dentro desta classificação. Excêntrica: O concepto penetra parcialmente o endométrio materno, mas mantém um certo contato com o lúmen uterino. Os roedores (ratos e ratos) e a coelha possuem este tipo de placentação. Intersticial: O embrião invade o endométrio, perde contato com o lúmen uterino, e ao crescer o lúmen uterino se oblitera. Os humanos e a maioria dos primatas mostram este tipo de placenta. Distribuição das vilosidades As vilosidades que formam a interface materno-fetal podem estar distribuídas de maneira diferente ao longo da superfície dos corioalantóides, pelo qual a placenta pode ser classificada como (figura 8): Difusa: Neste tipo de placenta as vilosidades estão distribuídas ao comprimento de toda a superfície do córion (corioalantóides) de maneira uniforme. As placentas de suínos e equinos se enquadram nesta classificação, embora, nesta última espécie, as vilosidades formem estruturas mais ramificadas, que são chamadas microcotilédones (figura 10). Zonal: Esta placenta se apresenta nos carnívoros domésticos, tanto caninos como felinos. As vilosidades que determinam a zona de troca de nutrientes e resíduos, e de ligação com o endométrio são delimitadas de forma a formar uma cintura central em torno do feto (figura 9). Distingue-se também uma segunda região chamada paraplacenta, que se localiza em ambos lados deste “cinto”, e do qual a função não é inteiramente conhecida, embora sabe-se que desempenha um papel importante na troca de ferro da mãe para o feto. As extremidades laterais dos corioalantóides nestas placentas não possuem vilosidades por isso não se ligam ao endométrio. Uma terceira região é a zona transparente nas extremidades distais do córion que tem pouca vascularização. Esta zona pode estar envolvida na absorção de materiais diretamente do lúmen uterino (figura 11). Cotiledonária: É o tipo de placentação que se encontra presente nos ruminantes (ovinos, caprinos e bovinos). As vilosidades coriônicas nestas espécies são agrupadas em pequenas áreas do córion chamadas cotilédones, que se interdigitam e fundem-se parcialmente com locais delimitados no endométrio chamados carúnculas, formando, em conjunto, estruturas conhecidas como placentomas. Cabe destacar que as carúnculas carecem de glândulas endometriais, que só estão presentes nas porções inter-carun- culares do endométrio. Os placentomas, por sua vez, são altamente vascularizados e são remodelados com o progresso da gestação, ramificando-se para aumentar a superfície de troca e o fluxo sanguíneo para aumentar os requisitos do feto em crescimento. Nas zonas inter-carunculares, a placenta é ligada ao endométrio por meio de sistemas de adesão superficial que envolvem glicoproteínas. Acredita-se que a adesão do concepto com o endométrio (carúnculas) é estabelecida em torno de 30 dias em ovinos e 40 dias em bovinos. (figuras 13 a 17). Discoidal: Nestas placentas, as vilosidades agrupam-se numa área circular ou oval, formando uma estrutura discoidal. Este tipo de placenta é encontrada principal- mente em coelhas, roedores e primatas, incluindo os humanos. Histologicamente Esta classificação considera o número de camadas de tecido que compõem a placenta e que separam a circulação materna da circulação fetal (tabela 3). O número máximo é de seis camadas, três do lado fetal (córion, tecido intersticial e endotélio do vaso sanguíneo) e três do lado materno (epitélio endometrial, tecido intersticial e endotélio vascular) (figura 19 e tabela 3). O modo de distinguir e nomear os diferentes tipos de placenta nesta classificação é usando como prefixo a camada materna que está em contato com o córion fetal. As diferentes placentas baseados em sua histologia são as seguintes (figura 19): Epiteliocorial: É o menos íntimo entre os tipos de placentas (figura 20). Estas placentas conservam intactas as seis camadas de tecido, portanto que mantêm as circulações materna e fetal mais separadas, e consideradas como as mais impermeáveis. Este tipo de placenta está presente na porca e égua. Lembre-se de que as placentas da porca e da égua são diferentes e as vilosidades ocupam uma grande proporção da área de superfície do córion (figura 19 A). Também apresenta-se nos ruminantes, no entanto, as placentas dos ruminantes apresentam algumas características particulares que as colocam como um subgrupo e se chamam sinepiteliocorial ou sindesmocorial (figura 19 B). Na vaca, este tipo apresenta-se nos primeiros 2-3 meses de gestação. Além da característica de erosão parcial do epitélio endometrial, um tipo de célula único é encontrado na placenta de ruminantes. Essas células são chamadas células gigantes binucleadas. Como o nome indica, elas são caracterizadas como bastante grandes e com dois núcleos. Na placenta dos ruminantes, algumas células do epitélio coriônico conhecidas como células binucleadas, se fundem com algumas células do epitélio endometrial, criando inicialmente células gigantes trinucleadas e mais tarde placas ou sincícios multinucleados. Estes sincícios têm em consequência uma origem tanto fetal como materna, que criam lugares delimitados nos quais em vez de existir intacta uma camada de epitélio coriônico e outra de epitélio endometrial, encontra-se uma só camada que combina as duas origens. As células gigantes binucleadas migram e mudam seu número ao longo da gestação em forma dinâmica. Este tipo celular é importante porque secretam uma variedade de hormônios. Células gigantes binucleadas aparecem por volta do dia 14 na ovelha e entre os dias 18 e 20 na vaca. Endoteliocorial: 5 camadas. Neste tipo de placentação o córion fetal está em contato direto com o endotélio vascular do endométrio graças à erosão do epitélio e do tecido conectivo endometrial (tecido intersticial) durante a implantação (figura 19 C). De modo que o intercâmbio de substâncias e resíduos só requer atravessar quatro camadas de tecidos. Este tipo de placenta é presente principalmente em cães e felinos. Nota-se nas figuras 19 C e 21 que este tipo de placenta é mais íntimo do que a placenta epiteliocorial porque o epitélio endometrial não existe mais. Hemocorial: 3 camadas (figura 22). Aqui o epitélio coriônico está intacto e entra em contato direto com o sangue materno em regiões onde formam reservatórios de sangue semelhantes a poços (figura 19 D). O intercâmbio de substâncias e resíduos entre a mãe e o feto é mais direto uma vez que é necessário atravessar apenas três camadas para chegar até à circulação fetal. Algumas espécies de primatas, incluindo o ser humano e os roedores possuem este tipo de placentação. MEMBRANAS EXTRAEMBRIONÁRIAS EM AVES Ao mesmo tempo que se estabelece o corpo embrionário e os esboços de cada um dos órgãos começam a gerar-se, torna-se imperioso garantir a sobrevivência do embrião. Tenha-se em conta que nas aves todo o necessário para o desenvolvimento é encontrado no ovo pelo que deve-se reforçar a eficácia das estruturas criadas para garantir o objetivo a que se destina. O exterior é fornecido apenas com o O2; emite CO2 e vapor de água no exterior (perda de 15% da água durante a incubação inicial). Além disso, o neonato não é imaturo, como nos anfíbios, mas está em um estádio maduro juvenil. Como indicado, são quatro as problemáticas a que deve fazer frente o embrião: prover-se de um meio que garanta o desenvolvimento volumétrico, amortecendo os movimentos físicos excessivos que possam traumatizá-lo e evitar a dessecação; assegurar que os nutrientes (vitelo e albúmen) sejam incorporados de forma correta no interior do embrião; assegurar o intercâmbio de gases; e eliminar substâncias tóxicas derivadas do metabolismo proteico. Para atender estas necessidades são desenvolvidas uma série de membranas extrambrionárias que se vão expandindo progressivamente pelo interior do ovo. A dureza da casca e sua relativa impermeabilidade protege-o igualmente da intempérie terrestre. -/- Figura 23: Evolução das membranas extraembrionárias de galinha (3 e 10 dias de incubação). -/- Saco vitelino: o saco vitelino é a primeira membrana extraembrionária em formação. Aparece como consequência direta da gastrulação: as camadas germinativas que se formam ao nível do disco embrionário expandem-se progressivamente contornando o vitelo. Assim, as células provenientes da área opaca (equivalente ao trofoblasto dos mamíferos) migram sobre o vitelo, terminando quase por cobrir, o mesmo ocorre com o endoderma mais internamente, formando-se assim um saco bilaminar. Posteriormente, o mesoderma se interpõe entre ambos, progredindo igualmente no sentido distal, rodeando o endoderma e aderindo-se ao mesmo e ao equivalente de trofoblasto. Ao estabelecer-se o celoma, o saco é constituído pelo endoderma e folha esplâncnica do mesoderma lateral. Este mesoderma vai progredindo no sentido distal e se vasculariza profunda- mente; os vasos distais se anastomosam formando um anel vascular denominado seio terminal, que marca o limite do mesoderma em expansão. Assim, sobre o vitelo é distinguível um área distal não vascularizada (área vitelina) e uma área proximal vascularizada (área vasculosa) que vai ficando progressivamente maior. Ao sexto dia de incubação mais da metade da superfície do vitelo foi envolvido pelo mesoderma. Os nutrientes do vitelo são absorvidos e desdobrados a componentes mais simples por enzimas produzidas pelo endoderma, sendo incorporados aos vasos vitelinos que os veicularão até o coração, que os impulsionará a todo o embrião. Durante a fase embrionária (até ao sexto dia de incubação), o oxigênio do exterior chega até a área vasculosa por difusão, incorporando-se daqui ao embrião; além disso, durante a primeira semana, as alterações na composição e volume do vitelo fazem que se disponha flutuando sobre o albúmen, o que faz com que a área vasculosa fique em contato com a casca, favorecendo-se assim a respiração. O intestino primitivo se instaura a partir das porções mais proximais do saco vitelino à vez que o corpo é fechado (2º-3º dia). O saco vitelino vai regredindo à medida que se vão esgotando os nutrientes do vitelo que aloja. Pouco antes do nascimento é incorporado à cavidade corporal como divertículo vitelino que fica unido ao jejuno; o divertículo vitelino persiste até seis dias após o nascimento, constituindo uma fonte adicional de nutrientes. -/- Figura 24: Feto de galinho ao fim, perto de ser eclodido. -/- mnios: no segundo dia (-30 horas) de incubação se formam as dobras amnióticas na somatopleura extraembrionária, perto do disco embrionário. Progridem dorsalmente, terminando por convergir e fundir-se cerca de 72 horas de incubação, coincidindo com o fechamento corporal, assim sendo constituído o âmnios, que terminará perdendo todo o contato com o córion. A cavidade amniótica que limita está cheia de um líquido seroso que garante que o embrião seja desenvolvido em um meio aquoso; este líquido é secretado pelo âmnios, mas também composto por substâncias formadas pelos rins, cavidade oral e aparelho respiratório. Córion: após a formação do celoma e o estabelecimento e fusão das dobras amnióticas, a parte da somatopleura extraembrionária que fica mais periférica constitui o córion (também denominado serosa nas aves); permanece formada pela área opaca expandida e mesoderma somático. Progressivamente vai aderindo-se à membrana testácea interna deslocando o albúmen; sobre o dia 12 termina por cobrir toda a superfície interna da casca. Intervém na troca gasosa com o meio ambiente através dos poros da casca e na captação do cálcio desta. Alantóides: o alantóide inicia a sua formação no dia 3 de incubação. Cresce rapidamente, ocupando o espaço exocelômico, terminando por cobrir o âmnios e saco vitelino. Progressivamente, entre os dias 4 a 10, sua parte mais externa se funde com o córion, formando-se o alantocórion, membrana trilaminar que cobrirá a superfície interna da casca, aderindo-se à membrana testácea interna, cujo mesoderma (esplâncnico) se vasculariza intensamente. A partir do dia 7 substitui completamente a área vasculosa como órgão respiratório, sendo garantido o aumento gradual das necessidades de troca gasosa na fase fetal do desenvolvimento (desde o dia 8), de rápido crescimento. A capacidade de capilarização desta membrana é muito maior do que a do saco vitelino. Na cavidade alantóica acumula-se a urina produzida pelos rins, afastando os produtos tóxicos do embrião; a membrana também age sobre este fluido intervindo na manutenção do equilíbrio hídrico e mineral do embrião. -/- Figura 25: Formação do saco vitelino. Limite entre a área vascular e avascular. Seio terminal. -/- O albúmen perde água rapidamente e torna-se menos volumoso e mais viscoso, terminando por desaparecer progressivamente. A ligação do alantocórion à membrana testácea interna faz com que seja marginalizado para uma posição periférica, no polo agudo do ovo. Aqui, o alantocórion que o rodeia constitui o saco do albúmen. O albúmen é a principal fonte de água e proteínas. A água é incorporada ao vitelo, o que, ao tornar-se mais volumoso, provoca que, entre os dias 3 e 4, se rompa a membrana vitelina; apenas restos mortais devem permanecer entre o saco vitelino e o albúmen. Dentro do saco vitelino, a água se acumula principalmente sob o embrião -fluido subembrionário-; este fluido atinge o seu volume máximo (15 ml) no dia 6. As proteínas serão incorporadas principalmente a partir de no dia 12, seja através do saco vitelino, do saco do albúmen ou por ingestão de líquido amniótico, dada a comunicação seroamniótica que se estabelece. Na galinha, a eclosão ocorre aos 21 dias de incubação. REFERÊNCIAS BIBLIOGRÁFICAS -/- Anotações de aulas de Embriologia Básica, Prof. Dr. Edson João da Silva, UFRPE, 2021. BAZER, Fuller W. et al. Novel pathways for implantation and establishment and maintenance of pregnancy in mammals. MHR: Basic science of reproductive medicine, v. 16, n. 3, p. 135-152, 2009. CARTER, Anthony M. Evolution of placental function in mammals: the molecular basis of gas and nutrient transfer, hormone secretion, and immune responses. Physiological Reviews, 2012. CARTER, A. M.; ENDERS, A. C. Placentation in mammals: Definitive placenta, yolk sac, and paraplacenta. Theriogenology, v. 86, n. 1, p. 278-287, 2016. CONSTANTINESCU, G.M.; SCHATTEN, H. Comparative reproductive biology. Carlton: Blackwell Publishing, 2007. 402p. Avicultura: Formação do Ovo. Desenvolvimento Embrionário e Diferenciação Sexual nos Animais Domésticos. Disponível em:. Acesso em: Dezembro de 2021. Diferenciação e Determinação Sexual dos Animais. Fisiologia do Ciclo Estral dos Animais Domésticos. Emanuel Isaque Cordeiro da Silva, 2021. Manejo na Avicultura: Postura, Iluminação e Incubação dos Ovos. Transporte de Gametas, Fertilização e Segmentação. FERRER‐VAQUER, Anna; HADJANTONAKIS, Anna‐Katerina. Birth defects associated with perturbations in preimplantation, gastrulation, and axis extension: from conjoined twinning to caudal dysgenesis. Wiley Interdisciplinary Reviews: Developmental Biology, v. 2, n. 4, p. 427-442, 2013. GALINA, Carlos; VALENCIA, Javier. Reproducción de los animales domésticos. 2006. GEISERT, Rodney D.; SPENCER, Thomas E. Placentation in Mammals. Springer, 2021. GINTHER, O. J. Reproductive Biology of The mare: Basic and Applied Aspects. 2. ed. Cross Plains, Wisconsin: Equiservices, 1992. GUILLOMOT, Michel. Cellular interactions during implantation in domestic ruminants. Journal of Reproduction and Fertility-Supplements only, n. 49, p. 39-52, 1995. KLEIN, C.; TROEDSSON, M. H. T. Maternal recognition of pregnancy in the horse: a mystery still to be solved. Reproduction, Fertility and Development, v. 23, n. 8, p. 952-963, 2011. MIGLINO, Maria Angelica et al. The carnivore pregnancy: the development of the embryo and fetal membranes. Theriogenology, v. 66, n. 6-7, p. 1699-1702, 2006. MOFFETT, Ashley; LOKE, Charlie. Immunology of placentation in eutherian mammals. Nature Reviews Immunology, v. 6, n. 8, p. 584-594, 2006. PRETZER, S. D. Canine embryonic and fetal development: A review. Theriogenology, v. 70, n. 3, p. 300-303, 2008. SENGER, Phillip L. et al. Pathways to pregnancy and parturition. Current Conceptions, Inc., 1615 NE Eastgate Blvd., 2012. SOZEN, Berna; CAN, Alp; DEMIR, Necdet. Cell fate regulation during preimplantation development: a view of adhesion-linked molecular interactions. Developmental biology, v. 395, n. 1, p. 73-83, 2014. SPENCER, Thomas E. et al. Pregnancy recognition and conceptus implantation in domestic ruminants: roles of progesterone, interferons and endogenous retroviruses. Reproduction, fertility and development, v. 19, n. 1, p. 65-78, 2006. VERSTEGEN-ONCLIN, K.; VERSTEGEN, J. Endocrinology of pregnancy in the dog: a review. Theriogenology, v. 70, n. 3, p. 291-299, 2008. WOODING, Peter; BURTON, Graham. Comparative placentation: structures, functions and evolution. Springer Science & Business Media, 2008. FIXAÇÃO DO ASSUNTO -/- 1. Defina e diferencie os processos de desenvolvimento embrionário precoce, alonga- mento e gastrulação. -/- 2. O que é implantação? Caracterize as fases do processo de implantação. -/- 3. Qual a importância do acúmulo de líquido no interior do blastocele? Qual a importân- cia da eclosão do blastocisto? -/- 4. Caracterize os três tipos de implantação e, depois, explique e diferencie os meios de implantação nas fêmeas domésticas. -/- 5. Defina e caracterize os meios de reconhecimento materno da gestação (RMG) nos animais domésticos. -/- 6. O que diferencia o RMG em ruminantes e suínos? -/- 7. Qual o papel do estradiol no RMG em porcas? O que ocorre quando a porca não fica gestante? -/- 8. Explique o RMG em cães e gatos. -/- 9. Defina placentação e sua importância para a reprodução dos animais domésticos. -/- 10. Quais são as classificações da placentação? Classifique a placentação das fêmeas domésticas. -/- 11. Caracterize e diferencie o processo de placentação em fêmeas domésticas. -/- 12. Observe a figura e responda o que se pede:. (shrink)

HISTÓRIA DA SOCIOLOGIA: O DESENVOLVIMENTO DA SOCIOLOGIA I -/- A SOCIOLOGIA CONTEMPORÂNEA -/- HISTORY OF SOCIOLOGY: THE DEVELOPMENT OF SOCIOLOGY I THE SOCIOLOGY CONTEMPORANY -/- Emanuel Isaque Cordeiro da Silva – IFPE-BJ, CAP-UFPE e UFRPE. E-mails: [email protected] e [email protected] WhatsApp: (82)98143-8399. -/- PREMISSA -/- Se até a década de 1960 podia-se falar em uma Sociologia dividida por países, após essa época, tendo em vista um processo significativo de circulação de informações pelos mais variados meios de comunicação, pode-se dizer que os (...) principais cientistas sociais se tornaram globalizados, assim como a literatura sociológica. As questões sociais, que até então podiam estar localizadas em países ou em blocos de países, também se tornaram mundializadas, e vários pensadores passaram a refletir sobre temas chamados de pós-modernos, hipermodernos ou simplesmente contemporâneos, e que afetam um país, uma região ou todo o mundo. A Sociologia contemporânea, porém, mantém uma relação significativa com as grandes vertentes da Sociologia anterior: • a marxista ou histórico-estrutural, com suas variações; • a durkheimiana ou funcionalista, com o desenvolvimento de um neofuncionalismo; • a weberiana ou compreensiva, com o desenvolvimento da fenomenologia e da hermenêutica; • a teórica e pragmática estadunidense, com variadas linhas. Além dessas vertentes, pensadores como Jean-Gabriel de Tarde e Georg Simmel, que estavam um tanto esquecidos, pelo menos no Brasil, em razão da ênfase em Émile Durkheim, num caso, e em Max Weber, em outro, retomaram seus lugares de destaque. Essas vertentes inspiraram outros tantos pensadores, que – refletindo sobre a realidade em que vivem, mesclando ou não contribuições de diferentes linhas teóricas e formulando uma série de conceitos – demonstram as possibilidades e a diversidade do pensamento sociológico e fazem a Sociologia avançar muito no processo de compreensão da realidade contemporânea. A combinação de diversas vertentes teóricas torna difícil fazer qualquer enquadramento ou mesmo tentar classificar determinados autores. Muitos analistas veem nisso uma crise de paradigmas na Sociologia contemporânea. Essa “crise” poderia ser entendida do ponto de vista epistemológico; entretanto, sempre houve diversidade de epistemologias na Sociologia. Acreditamos que essa diversidade epistemológica, de teorias, de objetos e de métodos, concorrentes ou não, na explicação de fenômenos sociais deve ser vista como indicativo de vigor, e não de decadência. Por fim, indico a seguir, em ordem alfabética, alguns dos pensadores e sociólogos contemporâneos cujo trabalho tem dado especial contribuição à Sociologia desenvolvida no Brasil: Alain Touraine (1925-), Anthony Giddens (1938-), Axel Honneth (1949-), Boaventura de Sousa Santos (1940-), David Harvey (1935-), Edgard Morin (1921-), François Dubet (1946), Gilles Lipovetsky (1944-), Howard S. Becker (1928-), Immanuel Wallerstein (1930-), István Mészáros (1930-2017), Jean Baudrillard (1929-2007), Jürgen Habermas (1929-), Manuel Castells (1942-), Marshall Bermann (1940-2013), Michael Löwy (1938-), Michel Maffesoli (1944-), Néstor García Canclini (1939-), Niklas Luhmann (1927-1998), Norbert Elias (1897-1990), Peter Ludwig Berger (1929-2017), Ralph Dahrendorf (1929-2009), Raymond Boudon (1934-2013), Richard Sennett (1943-), Serge Moscovici (1928 -2014), Thomas Luckmann (1927-2016), Ulrich Beck (1944-2015) e Zygmunt Bauman (1925-2017). -/- REFERENCIAL TEÓRICO -/- CUIN, C. H.; GRESLE, F. História da Sociologia. Trad. Roberto Leal Ferreira. São Paulo: Ensaio, 1994. -/- NERY, M. C. R. Sociologia contemporânea. 1ª ed. Curitiba: IESDE, 2007. -/- NOVA, S. V. Introdução a Sociologia. 6ª ed. São Paulo: Atlas, 2004. -/- SILVA, A. et al. Sociologia em movimento. 2ª ed. São Paulo: Moderna, 2016. -/- SBS - Sociedade Brasileira de Sociologia PUCRS - PPG em Ciências Sociais Avenida Ipiranga, 6681 - Partenon CEP: 90619-900 - Porto Alegre, RS [email protected] Emanuel Isaque Cordeiro da Silva © 2019 -/- Estimule a criatividade, respeite o direito autoral. (shrink)

These three volumes, entitled Essays On Values, bring together fortyone recent articles by researchers at the Nova Institute of Philosophy (IFILNOVA). They are a small sample of everything that, in the last four years, the Institute’s researchers have published, in English, in indexed journals and collections of essays with peer review. As a whole, they reflect very well the research work that is done at IFILNOVA. Section I. of Volume 1 gathers six articles that deal directly with the question “what (...) are values?”, the question that guides all the work of the institute’s different laboratories and research groups. The first article, by Susana Cadilha and Vítor Guerreiro, results from work developed in the Laboratory of Ethics and Political Philosophy (EPLab); the second, by João Constâncio, from the Lisbon Nietzsche Group; the third, by Alexandra Dias Fortes, from the Lisbon Wittgenstein Group; the third and fifth, by Nuno Fonseca, and Maria Filomena Molder, from the Aesthetics and Philosophy of Art Group of the Laboratory of Culture and Value (CultureLab); the last, by Erich H. Rast, from the Philosophy of Language and Argumentation Theory Group and the Lisbon Mind, Cognition & Knowledge Group of the Laboratory of Argumentation, Cognition, and Language (ArgLab). Section II. brings together three articles by members of the Lisbon Nietzsche Group. Since 2010, the Lisbon Nietzsche Group has completed several funded projects, and has established itself as a leading international research group on Nietzsche’s thought. The three articles demonstrate the crucial importance of the question of values in Nietzsche’s work, always thought from the perspective of the possibility of a “transvaluation of all values”. Maria João Mayer Branco’s article focuses on the value of introspection, and how Nietzsche anticipates Wittgenstein’s “expressivist” view of the “the Peculiar Grammar of the Word ‘I’” and the impossibility of private languages. Marta Faustino’s article considers the theme of affirmation and the value of life through the interpretation of Nietzsche’s reflection on truthfulness, intellectual honesty and courage in the light of Michel Foucault’s work on parrhesia. Pietro Gori’s article studies how Nietzsche creates a new anthropological ideal based on his enquiry into the values of the “good European”. The area of Wittgenstein studies has had a strong influence on the institute since the time when it was a philosophy of language institute. The Wittgensteinian distinction between facts and values was decisive in defining the question of values as the central issue of IFILNOVA’s research project, replacing the focus on philosophy of language. More recently, the focus of research at the Lisbon Wittgenstein Group has been on epistemic values, in particular in their connection with the question of religious belief. In Section III., Nuno Venturinha’s article examines, in the light of an epistemological standpoint, the way Wittgenstein thinks about the possibility of translation. Robert Vinten’s article argues that Wittgenstein’s thought contains elements for a critique of the concept of justice and of the liberal political visions of both Richard Rorty and Chantal Mouffe, despite the fact that both have drawn inspiration from Wittgenstein. Benedetta Zavatta’s article questions the value of mythology by thinking of it as a disease of language – not only in Wittgenstein, but also in a whole philosophical tradition that preceded him. The existence of a research group in ancient philosophy is a recent but very promising development in the life of IFILNOVA. Section IV. includes two articles by members of the group. Paulo Alexandre Lima’s article considers the critique of misology and the value of discourse in Plato’s Phaedo. Hélder Telo’s article examines the pedagogical and protreptic value of imperfection in Plato’s work. (shrink)

These three volumes, entitled Essays On Values, bring together fortyone recent articles by researchers at the Nova Institute of Philosophy (IFILNOVA). They are a small sample of everything that, in the last four years, the Institute’s researchers have published, in English, in indexed journals and collections of essays with peer review. As a whole, they reflect very well the research work that is done at IFILNOVA. Section I. of Volume 1 gathers six articles that deal directly with the question “what (...) are values?”, the question that guides all the work of the institute’s different laboratories and research groups. The first article, by Susana Cadilha and Vítor Guerreiro, results from work developed in the Laboratory of Ethics and Political Philosophy (EPLab); the second, by João Constâncio, from the Lisbon Nietzsche Group; the third, by Alexandra Dias Fortes, from the Lisbon Wittgenstein Group; the third and fifth, by Nuno Fonseca, and Maria Filomena Molder, from the Aesthetics and Philosophy of Art Group of the Laboratory of Culture and Value (CultureLab); the last, by Erich H. Rast, from the Philosophy of Language and Argumentation Theory Group and the Lisbon Mind, Cognition & Knowledge Group of the Laboratory of Argumentation, Cognition, and Language (ArgLab). Section II. brings together three articles by members of the Lisbon Nietzsche Group. Since 2010, the Lisbon Nietzsche Group has completed several funded projects, and has established itself as a leading international research group on Nietzsche’s thought. The three articles demonstrate the crucial importance of the question of values in Nietzsche’s work, always thought from the perspective of the possibility of a “transvaluation of all values”. Maria João Mayer Branco’s article focuses on the value of introspection, and how Nietzsche anticipates Wittgenstein’s “expressivist” view of the “the Peculiar Grammar of the Word ‘I’” and the impossibility of private languages. Marta Faustino’s article considers the theme of affirmation and the value of life through the interpretation of Nietzsche’s reflection on truthfulness, intellectual honesty and courage in the light of Michel Foucault’s work on parrhesia. Pietro Gori’s article studies how Nietzsche creates a new anthropological ideal based on his enquiry into the values of the “good European”. The area of Wittgenstein studies has had a strong influence on the institute since the time when it was a philosophy of language institute. The Wittgensteinian distinction between facts and values was decisive in defining the question of values as the central issue of IFILNOVA’s research project, replacing the focus on philosophy of language. More recently, the focus of research at the Lisbon Wittgenstein Group has been on epistemic values, in particular in their connection with the question of religious belief. In Section III., Nuno Venturinha’s article examines, in the light of an epistemological standpoint, the way Wittgenstein thinks about the possibility of translation. Robert Vinten’s article argues that Wittgenstein’s thought contains elements for a critique of the concept of justice and of the liberal political visions of both Richard Rorty and Chantal Mouffe, despite the fact that both have drawn inspiration from Wittgenstein. Benedetta Zavatta’s article questions the value of mythology by thinking of it as a disease of language – not only in Wittgenstein, but also in a whole philosophical tradition that preceded him. The existence of a research group in ancient philosophy is a recent but very promising development in the life of IFILNOVA. Section IV. includes two articles by members of the group. Paulo Alexandre Lima’s article considers the critique of misology and the value of discourse in Plato’s Phaedo. Hélder Telo’s article examines the pedagogical and protreptic value of imperfection in Plato’s work. (shrink)

Review of Felice C. Frankel's "The visual elements—design: a handbook for communicating science and engineering.".

In 1924, the Munich-school phenomenologist Moritz Geiger argued that there are dynamic essences. His two examples are the tragic, and being human, his main ideas are that what it takes to be tragic varies over time historically and that what makes an organism human varies across different stages of its ontogenetic development. He hence points to two ways in which essences may be dynamic, that is, subject to change. The current paper takes Geiger’s view seriously and assumes that it poses (...) an explanatory challenge for the, then and now, standard view that essences are ‘Platonic’, i.e. cannot be subject to change. In the first part of the paper, I introduce Geiger’s view and a bit of its historical context. In the second, I first formulate the challenge it poses to the standard ‘platonic’ view of essence, then discuss how this challenge can be met by a contemporary view of essence discussing three potential responses. The first relies on a notion of relativized essence, the second on the distinction between determinables and determinates, the third and last one on multidimensional properties. Finally, I argue that the last of these three proposals may be preferable to the other two. (shrink)

Brain-related diseases are among the most difficult diseases due to their sensitivity, the difficulty of performing operations, and their high costs. In contrast, the operation is not necessary to succeed, as the results of the operation may be unsuccessful. One of the most common diseases that affect the brain is Alzheimer’s disease, which affects adults, a disease that leads to memory loss and forgetting information in varying degrees. According to the condition of each patient. For these reasons, it is important (...) to classify memory loss and to know the patient at what level and his assessment of Alzheimer's disease through CT scans of the brain. In this thesis, we review ways and techniques to use deep learning classification to classifying the Alzheimer's Disease The proposed method used to improve patient care, reduce costs, and allow fast and reliable analysis in large studies. The model will be designed using Python language for implementing the system, which is very useful for doctors, classifying the Alzheimer's Disease, was used. The model used 70% from image for training and 30% from image for validation, our trained model achieved an accuracy of 100% on a held-out test set. (shrink)

Background: There is no doubt that strawberry diseases are one of the most important reasons that led to the destruction of strawberry plants and their crops. This leads to obvious damage to these plants and they become inedible. Discovering these diseases after a good step for proper and correct treatment. Determining the treatment with high accuracy depends on the method used in the diagnosis. Correctly, expert systems can greatly help in avoiding damage to these plants. The expert system correctly diagnoses (...) strawberry disease to make it easier for farmers to find the right treatment based on the appropriate diagnosis. Objectives: The main goal of this expert system is to get the appropriate diagnosis of disease and the correct treatment. Methods: In this paper the design of the proposed Expert System which was produced to help Farmers and students interested in agriculture strawberry in diagnosing many of the strawberry diseases such as: Leaf Spots, Grey Mold, Red Stele/Red Core, Wilt, Powdery Mildew, Alternaria Spot, Black Root Rot, Anthracnose (black spot), and Angular Leaf Spot. The proposed expert system presents an overview about strawberry diseases are given, the cause of diseases are outlined and the treatment of disease whenever possible is given out. CLIPS language was used for designing and implementing the proposed expert system. Results: The proposed strawberry diseases diagnosis expert system was evaluated by Farmers and they were satisfied with its performance. Conclusions: The Proposed expert system is very useful for Farmers with strawberry problem and students interested in agriculture strawberry. (shrink)

In this paper I take up the question of the nature of the doxastic attitudes we entertain while inquiring into some matter. Relying on a distinction between two stages of open inquiry, I urge to acknowledge the existence of a distinctive attitude of cognitive inclination towards a proposition qua answer to the question one is inquiring into. I call this attitude “hypothesis”. Hypothesis, I argue, is a sui generis doxastic attitude which differs, both functionally and normatively, from suspended judgement, full (...) belief, credences, and acceptance. In closing, I point to the epistemological significance of hypothesis. More specifically, I contend that holding an attitude of hypothesis enables us to respond rationally to peer disagreement, and I suggest that such an attitude offers a suitable articulation of the view, originally put forward by Philip Kitcher, that cognitive diversity in inquiry has epistemic benefits. (shrink)

Background: Mint is a grassy, perennial plant, belonging to the oral platoon, fast growing and spreading, its leaves are green in color, fragrant, tart, refreshing, square-shaped leg, bifurcated, erect, ranging in height from (10 - 201 cm). Home to Europe and Asia. The mint plant has many benefits, the most important of which are pain relief, treatment of gallbladder disorders, the expulsion of gases, anti-inflammatory, and relaxing nerves. While the mint plant is the ideal option for the start of gardens, (...) it is prone to some common diseases that affect the plant's growth. Objectives: The main goal of this expert system is to get the appropriate diagnosis of disease and the correct treatment. Methods: In this paper, the design of the proposed Expert System was produced to help Farmers and those interested in agriculture in diagnosing many of the Mint diseases such as Mint rust, Verticillium wilt, Anthracnose, Powdery mildew, Black Stem Rot, Stem and stolon canker, Septoria leaf spot. The proposed expert system presents an overview of mint diseases are given, the cause of diseases outlined and the treatment of disease whenever possible is given out. CLIPS Expert System language was used for designing and implementing the proposed expert system. Results: The proposed Mint diseases diagnosis expert system was evaluated by Agricultural Students at AL Azhar University and some friends interested in agriculture and they were satisfied with its performance. Conclusions: The proposed expert system is very useful for Farmers and those interested in agriculture. (shrink)

A recent paper by Bullock (2018) raises a dilemma for proponents of epistemic paternalism. If epistemic paternalists contend that epistemic improvements contribute to one’s wellbeing, then their view conflates with general paternalism. Instead, if they appeal to the notion of a distinctive epistemic value, their view is unjustified, in that concerns about epistemic value fail to outweigh concerns about personal sovereignty. In this chapter, I address Bullock’s challenge in a way that safeguards the legitimacy of epistemic paternalism, albeit restricting its (...) scope to a limited range of cognitive projects. After shedding light on a problem with how Bullock singles out cases to which the dilemma applies, I argue that there is at least one reasonable way of interpreting the notion of ‘personal autonomy’ which legitimates and justifies undertaking epistemically paternalistic interferences for one’s epistemic good. (shrink)

The Introduction highlights the three main themes of the book: (1) the ontological and epistemological status of everyday human consciousness, (2) the distribution of consciousness in the natural world, and (3) panpsychism. The individual contributions to the book are summarized and related literature is briefly discussed.

The surface grammar of reports such as ‘I have a pain in my leg’ suggests that pains are objects which are spatially located in parts of the body. We show that the parallel construction is not available in Mandarin. Further, four philosophically important grammatical features of such reports cannot be reproduced. This suggests that arguments and puzzles surrounding such reports may be tracking artefacts of English, rather than philosophically significant features of the world.

This paper tackles the problem of defining what a cognitive expert is. Starting from a shared intuition that the definition of an expert depends upon the conceptual function of expertise, I shed light on two main approaches to the notion of an expert: according to novice-oriented accounts of expertise, experts need to provide laypeople with information they lack in some domain; whereas, according to research-oriented accounts, experts need to contribute to the epistemic progress of their discipline. In this paper, I (...) defend the thesis that cognitive experts should be identified by their ability to perform the latter function rather than the former, as novice-oriented accounts, unlike research-oriented ones, fail to comply with the rules of a functionalist approach to expertise. (shrink)

This paper focuses on extant approaches to counteract the consumption of fake news online. Proponents of structural approaches suggest that our proneness to consuming fake news could only be reduced by reshaping the architecture of online environments. Proponents of educational approaches suggest that fake news consumers should be empowered to improve their epistemic agency. In this paper, we address a question that is relevant to this debate: namely, whether fake news consumers commit mistakes for which they can be criticized and (...) that they could easily avoid by reforming their doxastic conduct. Proponents of structural approaches, like R. Rini and B. Millar, have defended in different ways a negative answer to this question. In this paper, we criticize their views and suggest that individual users could improve on their epistemic practice by widening their information diet. (shrink)

Permissivism is the view that, sometimes, there is more than one doxastic attitude that is perfectly rationalised by the evidence. Impermissivism is the denial of Permissivism. Several philosophers, with the aim to defend either Impermissivism or Permissivism, have recently discussed the value of (im)permissive rationality. This paper focuses on one kind of value-conferring considerations, stemming from the so-called “truth-connection” enjoyed by rational doxastic attitudes. The paper vindicates the truth-connected value of permissive rationality by pursuing a novel strategy which rests on (...) two main planks: first, there is a distinction between a fine-grained and a coarse-grained type-individuation of belief-forming methods. Secondly, different kinds of decision-theoretic reasoning, i.e. expected-accuracy reasoning and accuracy-domination reasoning, must be paired with a fine-grained and a coarse-grained type-individuation of methods, respectively. I argue that while the first pair is wholly irrelevant to the question of the truth-connection, the second affords the means to a permissivist explanation of the truth-connected value of rationality. (shrink)

This provocation critiques the notion of long-term thinking and the claims of its proponents that it will help address failures in dominant conceptions of time, particularly in regard to environmental crises. Drawing on analyses of the Clock of the Long Now and Kim Stanley Robinson’s The Ministry for the Future, the article suggests that we be more wary of the concept’s use in what we might call chronowashing. Like the more familiar greenwashing, where environmental issues are hidden by claims to (...) be addressing the problem, the article explores how these examples of long-term thinking distract from extractivism, racism, and environmental injustice, making it harder to address the complexities involved. In particular, the article discusses examples where long-term thinking provides a veneer of environmental concern that actually disconnects from the work of building more equitable forms of relation. As a contrast, the article’s author asks: What is lost when we diagnose a problem as arising due to short-term thinking and propose long-term thinking as the solution? Against chronowashed environmental time, the author argues for more complex approaches that explicitly take into account the temporalities of inequality, political organization, ethical responsibilities and much else. The article engages with approaches to time that foreground the work needed to create time and move ethically within it, including Charles W. Mills’s white time and Kyle Powys Whyte’s kinship time. The author suggests that a stronger emphasis on the temporality of community, solidarity, and coalition—versus what James Hatley and Deborah Bird Rose have described as temporal narcissism—can better foreground the kinds of work that needs to be done, particularly by those with privilege. (shrink)

Tradition has it that first-person thought is somehow special. It is also commonplace to maintain that the first-person concept obeys a rule of reference to the effect that any token first-person thought is about the thinker of that thought. Following Annalisa Coliva and, more recently, Santiago Echeverri, I take the specialness claim to be the claim that thinking a first-person thought comes with a certain guarantee of its pattern of reference. Echeverri maintains that such a guarantee is explained by a (...) fairly flatfooted interpretation of the thinker-reflexive rule. I argue, however, that the explanatory aspirations of the thinker-reflexive rule are fulfilled only if we accept an epistemically loaded gloss on the notion of a thinker of a thought featuring the rule. That gloss is unpacked in terms of the subject’s ability to be acquainted with the phenomenal character of their thoughts. (shrink)

Despite contemporary moral philosophers' renewed attention to the moral significance of emotions, the attitudinal repertoire with which they equip the mature moral agent remains stunted. One attitude moral philosophers neglect (if not disown) is contempt. While acknowledging the nastiness of contempt, I here correct the neglect by providing an account of the moral psychology of contempt. In the process, I defend the moral propriety of certain tokens of properly person-focused contempt against some prominent objections -- among them, objections stemming from (...) Kantian worries that contempt is incompatible with the respect we owe to persons as such. (shrink)

This paper takes issue with the exemplarist strategy of fostering virtue development with the specific goal of improving its applicability in the context of education. I argue that, for what matters educationally, we have good reasons to endorse a liberal account of moral exemplarity. Specifically, I challenge two key assumptions of Linda Zagzebski’s Exemplarist Moral Theory (2017), namely that moral exemplars are exceptionally virtuous agents and that imitating their behavior is the main strategy for acquiring the virtues. I will introduce (...) and discuss the notions of enkratic exemplars and injustice illuminators and show that we have good reasons to consider them moral exemplars although they fail to satisfy (either of) the key assumptions. (shrink)

Francis Sparshott introduced the term ‘remote art’ in his 1982 presidential address to the American Society for Aesthetics. The concept has not drawn much notice since—although individual remote arts, such as palaeolithic art and the artistic practices of subaltern cultures, have enjoyed their fair share of attention from aestheticians. This paper explores what unites some artistic practices under the banner of remote art, arguing that remoteness is primarily a matter of some audience’s epistemic distance from a work’s context of creation. (...) I introduce palaeoart—the depiction of extinct prehistoric fauna and flora, especially from the Mesozoic—as a paradigmatic case of remote art, showing that its remoteness is secured both by the deceptively rich cognitive load required for its creation and appreciation, and by its existence at the margins of the institutional artworld, which ensures that this cognitive loading is largely obscured. Too often, remote art is not just inscrutable, it is invisible to us. (shrink)

INTRODUCTION THE PROBLEM OF THE BEING OF THE EGO AND THE FUNDAMENTAL PRESUPPOSITIONS OF ONTOLOGY "Mit dem cogito sum beansprucht Descartes, der Philosophic ...

How does microbiota research impact our understanding of biological individuality? We summarize the interdisciplinary summer school on "Microbiota, Symbiosis and Individuality: Conceptual and Philosophical Issues" (July 2019), which was supported by a European Research Council starting grant project "Immunity, DEvelopment, and the Microbiota" (IDEM). The summer school centered around interdisciplinary group work on four facets of microbiota research: holobionts, individuality, causation, and human health. The conceptual discussion of cutting-edge empirical research provided new insights into microbiota and highlights the value of (...) incorporating into meetings experts from other disciplines, such as philosophy and history of science. (shrink)

According to a recent account of epistemic authority proposed by Linda Zagzebski (2012), it is rational for laypersons to believe on authority when they conscientiously judge that the authority is more likely to form true beliefs and avoid false ones than they are in some domain. Christoph Jäger (2016) has recently raised several objections to her view. By contrast, I argue that both theories fail to adequately capture what epistemic authority is, and I offer an alternative account grounded in the (...) abilities that different kinds of authorities are required to possess. (shrink)

Abstract: The integration of Artificial Intelligence (AI) into medical imaging represents a transformative shift in healthcare, offering significant improvements in diagnostic accuracy, efficiency, and patient outcomes. This paper explores the application of AI technologies in the analysis of medical images, focusing on techniques such as convolutional neural networks (CNNs) and deep learning models. We discuss how these technologies are applied to various imaging modalities, including X-rays, MRIs, and CT scans, to enhance disease detection, image segmentation, and diagnostic support. Additionally, the (...) paper addresses the challenges faced in AI-driven medical imaging, including data quality, model interpretability, and ethical considerations. By examining recent advancements and real-world case studies, this paper provides insights into the current state of AI in medical imaging and its potential future directions. The findings highlight the ongoing evolution of AI technologies and their crucial role in advancing medical diagnostics and treatment strategies. (shrink)

Plant diseases are numerous in the world of agriculture. These diseases cause a lot of trouble to most farmers. Among these common diseases, we single out the diseases that affect the Passion fruit, which is affected by about seven diseases, with different symptoms for each disease. Today, technology is facilitating human life in all areas of life, and among these facilities are expert system, a computer program that uses artificial-intelligence methods to solve problems within a specialized domain that ordinarily requires (...) human expertise. The first expert system was developed in 1965 by Edward Feigen Baum and Joshua Lederberg of Stanford University in California, U.S. Dendral, as their expert system was later known, was designed to analyses chemical compounds. Expert systems now have commercial applications in fields as diverse as medical diagnosis, petroleum engineering, and financial investing and other areas, and with reference to expert systems and their importance to humans, an integrated expert system has been created in the agricultural field that diagnoses Passion diseases using CLIPS Expert System language. The system was used to design and implement the proposed expert system. The system facilitates the diagnosis of Passion -related diseases. There is no doubt that this expert system will help farmers and those involved in the agricultural field to diagnose Passion -related diseases. Objectives: is to help farmers diagnose Passion diseases in the correct way and how to treat these diseases. Method: The system contains a program project that diagnoses 7 diseases that affect Passion and the seven diseases are: Brown spot, Septoria spot, Root and crown rot, Fusarium wilt, Anthracnose, Woodiness virus, Scab. Results: The expert system was evaluated by farmers and praised for helping them with it. Conclusion: The expert system for diagnosing Passion diseases is effective and usable. (shrink)

This paper explores what happens when artists fail to execute their goals. I argue that taxonomies of failure in general, and of failed-art in particular, should focus on the attempts which generate the failed-entity, and that to do this they must be sensitive to an attempt’s orientation. This account of failed-attempts delivers three important new insights into artistic practice: there can be no accidental art, only deliberate and incidental art; art’s intention-dependence entails the possibility of performative failure, but not of (...) failed-art; and art’s intention-dependence is perfectly compatible with the role that luck plays in artistic creation. (shrink)

There is growing concern that decision-making informed by machine learning (ML) algorithms may unfairly discriminate based on personal demographic attributes, such as race and gender. Scholars have responded by introducing numerous mathematical definitions of fairness to test the algorithm, many of which are in conflict with one another. However, these reductionist representations of fairness often bear little resemblance to real-life fairness considerations, which in practice are highly contextual. Moreover, fairness metrics tend to be implemented in narrow and targeted toolkits that (...) are difficult to integrate into an algorithm’s broader ethical assessment. In this paper, we derive lessons from ethical philosophy and welfare economics as they relate to the contextual factors relevant for fairness. In particular we highlight the debate around acceptability of particular inequalities and the inextricable links between fairness, welfare and autonomy. We propose Key Ethics Indicators (KEIs) as a way towards providing a more holistic understanding of whether or not an algorithm is aligned to the decision-maker’s ethical values. (shrink)

This article introduces an account of moral education grounded in Zagzebski’s recent Exemplarist Moral Theory and discusses two problems that have to be solved for the account to become a realistic alternative to other educational models on the market, namely the limited-applicability problem and the problem of indoctrination. The first problem raises worries about the viability of the account in ordinary circumstances. The second charges the proposed educational model with indoctrinating students. The main goal of this article is to show (...) how an exemplar-based account of moral education can handle both problems without compromising its structure and upshot. (shrink)

“Wild Wise Weird” is an extraordinary collection of short stories that offers a delightful window into Vietnamese culture through the quirky and thought-provoking adventures of Kingfisher, the clever protagonist from the bird village. Vuong Quan Hoang masterfully weaves humor, satire, and social commentary into tales that are both entertaining and deeply reflective.

Philosophical suspicions about the place of shame in the psychology of the mature moral agent are in tension with the commonplace assumption that to call a person shameless purports to mark a fault, arguably a moral fault. I shift philosophical suspicions away from shame and toward its absence in the shameless by focusing attention on phenomena of shamelessness. In redirecting our attention, I clarify the nature of the failing to which ascriptions of shamelessness might refer and defend the thought that, (...) as an evasion of moral self-censure, shamelessness can be morally pernicious. Far from foregoing shame, I conclude, we should be mindful of its moral importance and unapologetic in its defense. (shrink)

Notes prises par Jacques Lagrange lors du cours d'anthropologie donné par Michel Foucault en 1954-1955 à l'École Normale Supérieure.

This paper confronts Zagzebski’s exemplarism with the intertwined debates over the conditions of exemplarity and the unity-disunity of the virtues, to show the advantages of a pluralistic exemplar-based approach to moral education (PEBAME). PEBAME is based on a prima facie disunitarist perspective in moral theory, which amounts to admitting both exemplarity in all respects and single-virtue exemplarity. First, we account for the advantages of PEBAME, and we show how two figures in recent Italian history (Giorgio Perlasca and Gino Bartali) satisfy (...) Blum’s definitions of ‘moral hero’ and ‘moral saint’ (1988). Then, we offer a comparative analysis of the effectiveness of heroes and saints with respect to character education, according to four criteria derived from PEBAME: admirability, virtuousness, transparency, and imitability. Finally, we conclude that both unitarist and disunitarist exemplars are fundamental to character education; this is because of the hero's superiority to the saint with respect to imitability, a fundamental feature of the exemplar for character education. (shrink)

The premise that every work belongs to an art-kind has recently inspired a kind-centred approach to theories of art. Kind-centred analyses posit that we should abandon the project of giving a general theory of art and focus instead on giving theories of the arts. The main difficulty, however, is to explain what makes a given kind an art-kind in the first place. Kind-centred theorists have passed this buck on to appreciative practices, but this move proves unsatisfactory. I argue that the (...) root of this dissatisfaction stems not from the act of kicking the can down the road, but from not kicking it far enough. The missing ingredient, I argue, is a notion of convention which does the work of marking the difference between art and non-art for a given physical medium. (shrink)

Studying consciousness requires contrasting conscious and unconscious perception. While many studies have reported unconscious perceptual effects, recent work has questioned whether such effects are genuinely unconscious, or whether they are due to weak conscious perception. Some philosophers and psychologists have reacted by denying that there is such a thing as unconscious perception, or by holding that unconscious perception has been previously overestimated. This article has two parts. In the first part, I argue that the most significant attack on unconscious perception (...) commits the criterion content fallacy: the fallacy of interpreting evidence that observers were conscious of something as evidence that they were conscious of the task-relevant features of the stimuli. In the second part, I contend that the criterion content fallacy is prevalent in consciousness research. For this reason, I hold that if unconscious perception exists, scientists studying consciousness could routinely underestimate it. I conclude with methodological recommendations for moving the debate forward. (shrink)

This article presents a fairness principle for evaluating decision-making based on predictions: a decision rule is unfair when the individuals directly impacted by the decisions who are equal with respect to the features that justify inequalities in outcomes do not have the same statistical prospects of being benefited or harmed by them, irrespective of their socially salient morally arbitrary traits. The principle can be used to evaluate prediction-based decision-making from the point of view of a wide range of antecedently specified (...) substantive views about justice in outcome distributions. (shrink)

Springer. We find in contemporary culture starkly contrasting estimates of the value of faith. On the one hand, for many people, faith is a virtue or positive human value, something associated with understanding, hope, and love, something to be inculcated, maintained, and cherished. On the other hand, for many people, faith is a vice, something associated with dogmatism, arrogance, and close-mindedness, something to be avoided at all costs. The papers included in this special (double) issue on approaches to faith explore (...) questions about faith in a variety of settings through a diverse range of examples, both secular and religious. The attempt to deepen our understanding of faith in the context of ordinary human relationships (e.g., between parents and children, friends, generals and their armies, business partners, citizens and the state), a commitment to ideals, or the pursuit of significant goals is clearly of general philosophical interest, as is the examination of potential connections between faith and topics such as trust or reliance. (shrink)

It is widely agreed that fiction is necessarily incomplete, but some recent work postulates the existence of universal fictions—stories according to which everything is true. Building such a story is supposedly straightforward: authors can either assert that everything is true in their story, define a complement function that does the assertoric work for them, or, most compellingly, write a story combining a contradiction with the principle of explosion. The case for universal fictions thus turns on the intuitive priority we assign (...) to the law of non-contradiction. My goal in this paper is to show that our critical and reflective literary practices set constraints on story-telling which preclude universal fictions. I will raise four stumbling blocks for universal fictionalists: the gap between saying and making true, our actual interpretive reactions to story-level contradictions, the criteria we accept for what counts as a story in our literary practices, and the undesirability of the universal fictionalist’s closure principles. (shrink)

Observers inspected normal, high quality color displays of everyday visual scenes while their eye movements were recorded. A large display change occurred each time an eye blink occurred. Display changes could either involve "Central Interest" or "Marginal Interest" locations, as determined from descriptions obtained from independent judges in a prior pilot experiment. Visual salience, as determined by luminance, color, and position of the Central and Marginal interest changes were equalized. -/- The results obtained were very similar to those obtained in (...) prior experiments showing failure to detect changes occurring simultaneously with saccades, flicker, or “mudsplashes” in the visual scene: Many changes were very hard to detect, and Marginal Interest changes were harder to detect than Central Interest changes. -/- Analysis of eye movements showed, as expected, that the probability of detecting a change depended on the eye’s distance from the change location. However a surprising finding was that both for Central and Marginal Interest changes, evenwhen observers were directly fixating the change locations (within 1 degree),more than 40% of the time they still failed to see the changes. It seems that looking at something does not guarantee you “ see” it. (shrink)

The Precautionary Principle (PP) is an influential principle of risk management. It has been widely introduced into environmental legislation, and it plays an important role in most international environmental agreements. Yet, there is little consensus on precisely how to understand and formulate the principle. In this paper I prove some impossibility results for two plausible formulations of the PP as a decision-rule. These results illustrate the difficulty in making the PP consistent with the acceptance of any trade-offs between catastrophic risks (...) and more ordinary goods. (shrink)

While it seems hard to deny the epistemic significance of a disagreement with our acknowledged epistemic peers, there are certain disagreements, such as philosophical disagreements, which appear to be permissibly sustainable. These two claims, each independently plausible, are jointly puzzling. This paper argues for a solution to this puzzle. The main tenets of the solution are two. First, the peers ought to engage in a deliberative activity of discovering more about their epistemic position vis-à-vis the issue at stake. Secondly, the (...) peers are permitted to do so while entertaining a sui generis doxastic attitude of hypothesis. (shrink)

This chapter introduces a novel account of fake news and explains how it differs from other definitions on the market. The account locates the fakeness of an alleged news report in two main aspects related to its production, namely that its creators do not think to have sufficient evidence in favor of what they divulge and they fail to display the appropriate attitude towards the truth of the information they share. A key feature of our analysis is that it does (...) not require that fake news must be circulated with the intention to deceive one’s audience. In this way, our account overcomes a potential limitation of the current philosophical discussion about fake news, which appears to individuate the main problem with this phenomenon in the fact that fake news consumers are misled and misinformed. In contrast, the proposed analysis shows that an additional (and perhaps equally fundamental) problem uncovered by the spread of fake news is a widespread pathological relationship with information, one on which we consume information not to satisfy our interest in the truth but to strengthen our social identities and quench our hunger for social recognition. (shrink)

The article investigates the significance of the so-called phenomenon of apparent faultless disagreement for debates about the semantics of taste discourse. Two kinds of description of the phenomenon are proposed. The first ensures that faultless disagreement raises a distinctive philosophical challenge; yet, it is argued that Contextualist, Realist and Relativist semantic theories do not account for this description. The second, by contrast, makes the phenomenon irrelevant for the problem of what the right semantics of taste discourse should be. Lastly, the (...) following dilemma is assessed: either faultless disagreement provides strong evidence against semantic theories; or its significance should be considerably downplayed. (shrink)