Bu [makalede], nihai olarak kesin bir sonucu olduğunu iddia etmemekle birlikte, ateizm için geliştirebileceğim en iyi argümanı öne sürmeye çalışacağım ve ortaya koyacağım şeyin, Tanrı’nın varlığına dair yürütülen tartışmaların herhangi bir kısmındaki, en iyi argüman olduğunu iddia edeceğim.

This paper consider three families of arguments for atheism. First, there are direct arguments for atheism: arguments that theism is meaningless, or incoherent, or logically inconsistent, or impossible, or inconsistent with known fact, of improbable given known fact, or morally repugnant, or the like. Second, there are indirect arguments for atheism: direct arguments for something that entails atheism. Third, there are comparative arguments for atheism: e.g., arguments for the view that (atheistic) naturalism is more theoretically virtuous than theism.

In this paper, I examine Kant’s discussion of ‘the cosmological argument’ in The Critique of Pure Reason, Transcendental Doctrine of Elements, Second Part, Second Division, Book 2, Chapter Three, Section Five (‘The Impossibility of a Cosmological Proof of the Existence of God’). While there are other places where Kant provides related discussions of ‘the cosmological argument’—e.g. in The Only Possible Argument in Support of a Demonstration of the Existence of God, Lectures on Philosophical Theology, and Religion within the Limits of (...) Reason Alone—I do not attempt to consider any of these further works in this paper. First, I argue that it is not true that cosmological arguments depend upon ontological arguments, and that Kant is simply mistaken when he argues that ‘the cosmological argument’ ‘assumes’ ‘the ontological argument’. Second, I argue that Kant does not provide a compelling critique of cosmological arguments to the conclusion that there is an absolutely necessary being. (shrink)

An object-based correspondence theory of truth holds that a truth-bearer is true whenever its truth conditions are met by objects and their properties. In order to develop such a view, the principal task is to explain how truth-bearers become endowed with their truth conditions. Modern versions of the correspondence theory see this project as the synthesis of two theoretical endeavours: basic metasemantics and compositional semantics. Basic metasemantics is the theory of how simple, meaningful items (e.g. names and concepts) are endowed (...) with their contributions to truth conditions, and compositional semantics is the theory of how the meanings of simple items compose to generate (among other things) the truth conditions of sentences. Understanding truth along these broad lines was once popular; it was first championed by Field (1972). However, the once-popular conception of its tasks included an over-ambitious view of basic metasemantics. It was thought that reference needed to be analyzed (or reduced a posteriori) in terms of more fundamental, non-semantic relations (e.g. causal relations, indication, or teleological relations, in the case of mental representation). Obstacles in providing such an analysis engendered skepticism towards this understanding of truth and eventually gave way to its deflationary competitors. This dissertation aims to defend the modern, object-based correspondence theory against its rivals—especially deflationism. Chapter one provides a historically-grounded overview of the theory. Chapter two identifies two points of contrast between the correspondence theorist and the deflationist: they employ different orders of explanation for the variety of semantic phenomena, and they (traditionally) take different attitudes towards the prospects of reduction. Situating the dialectic in this way allows me to develop a middle ground: a moderate version of inflationism that takes the inflationary explanatory structure and combines it with a non-reductive, pluralist approach to basic metasemantics. Chapter three expands on the details of this pluralist account of reference. Chapter four contrasts the view with another rival approach to basic metasemantics: metasemantic interpretationism. And finally, chapter five applies the theory to answer another question of broad philosophical interest: what role does our conception of truth play in inquiry about the world? (shrink)

This chapter discusses norms of assertion. I defend the view that the sole constitutive norm of assertion is that you should not assert what you do not believe. I also discuss the views of some--e.g. Grice, Williamson--who have defended the stronger view that the sole constitutive norm of assertion is that you should not assert what you do not know.

Sceptical theists--e.g., William Alston and Michael Bergmann--have claimed that considerations concerning human cognitive limitations are alone sufficient to undermine evidential arguments from evil. We argue that, if the considerations deployed by sceptical theists are sufficient to undermine evidential arguments from evil, then those considerations are also sufficient to undermine inferences that play a crucial role in ordinary moral reasoning. If cogent, our argument suffices to discredit sceptical theist responses to evidential arguments from evil.

This article is part of a For-Discussion-Section of Methods of Information in Medicine about the paper "Biomedical Informatics: We Are What We Publish", written by Peter L. Elkin, Steven H. Brown, and Graham Wright. It is introduced by an editorial. This article contains the combined commentaries invited to independently comment on the Elkin et al. paper. In subsequent issues the discussion can continue through letters to the editor.

In the novel A Burnout-Out Case, Graham Greene argues for an intimate relationship between burnout and happiness. The novel claims that a life worth living is a continuous balancing between something painful, e.g. burnout and something desirable, e.g. happiness. In this essay, I try to make a case for the happiness of burnout. By examining the case story of a young artist, who suffered from burnout, I describe how such suffering might open up for a necessary reevaluation of the (...) values that actually make sense. Such creation of new values is what eventually leads to more happy moments, not happiness per se. This essay provides a philosophical reflection regarding the relationship between happiness and burnout in order to say something regarding which life is worth living. (shrink)

This is a forthcoming section for the book "Theism and Atheism: Opposing Arguments in Philosophy", edited by Graham Oppy, Gregory Dawes, Evan Fales, Joseph Koterski, Mashhad Al-Allaf, Robert Fastiggi, and David Shatz. I was asked to write a brief essay on whether naturalism or theism can successfully explain the distribution of suffering in our world. Wheras another section covers the possibility that suffering is evidence against theism, my essay is concerned only with the ability for either naturalism or theism (...) to explain suffering. I argue that, for naturalists, suffering is not to be explained by either philosophers of religion or theologians. Instead, naturalists believe that suffering should be explained by the cognitive and social sciences, perhaps in conjunction with political philosophy and philosophy of mind. Moreover, naturalists may take suffering to be an important reason for action. In a world without a transcendent, supernatural being to watch over us, we can only depend upon each other to ameliorate existing conditions, to the extent that they can be ameliorated. On the other hand, theistic explanations of the distibution of suffering slip very easily into problematic theologies when they try to offer explicit explanations for suffering. For example, the world's most vulnerable people are often those who suffer the most, whereas oppressors are often able to prosper. That is, theistic explanations of our world's suffering easily slip into, e.g., the just world fallacy, racist ideology (i.e., that God favors some race(s) of people over others), or patriarchal ideology. Instead of offering an explicit explanation, theists should instead be skeptical theists -- i.e., they should argue that an explanation for our world's suffering is beyond our ken. While skeptical theism avoids the aforementioned problematic implications, if skeptical theism is true, then our world's suffering cannot be fully explained. (shrink)

One shortcoming of the chain rule is that it does not iterate: it gives the derivative of f(g(x)), but not (directly) the second or higher-order derivatives. We present iterated differentials and a version of the multivariable chain rule which iterates to any desired level of derivative. We first present this material informally, and later discuss how to make it rigorous (a discussion which touches on formal foundations of calculus). We also suggest a finite calculus chain rule (contrary to Graham, (...) Knuth and Patashnik's claim that "there's no corresponding chain rule of finite calculus"). (shrink)

In 'Metaphysics IX.6' (1048b 18-35) Aristotle presents a test to distinguish between "kinesis" and "energeia," based on relations between the perfective and the imperfective aspect of the verb. This passage has been interpreted as drawing a linguistic distinction between classes of verbs (e.g., stative verbs) by means of a linguistic criterion (Ackrill, Graham). But such an interpretation is in conflict with the text. Aristotle's test must, therefore, be understood as a metaphysical criterion between items in the world (rather than (...) lingual items) by means of a metaphysical criterion, exploiting properties of these items. These items are events, and 'Metaphysics IX.6' exhibits Aristotle's awareness to certain topics discussed in modern event ontology. (shrink)

Tarihte herhalde çok az soru Tanrı’nın varlığı sorusu kadar sık sorulmuş, çok yanıtlanmış ve verilen birbirinden farklı onca yanıta rağmen kesin bir sonuca ulaştırılamayıp tartışılmaya devam etmiştir. Yine de geçmişe dönüp baktığımızda bu soruya verilen farklı yanıtların farklı uygarlıkların inşa edilmesine, bazılarının yıkılmasına, acımasız çatışmalara ve her şeye rağmen kucaklaşmalara da vesile olduğunu görüyoruz. Tanrı var mı? Varsa onu nasıl bilebiliriz? Tanrı yoksa her şey mubah mı? İnsan aklı ilahi olanı kavrayabilir mi? Tanrı’nın varlığı ahlaklı olmanın şartı mı? Evren akıllı (...) bir tasarımcının imzasını taşıyor mu? Bu kitapta felsefeci William David Beck, bu sorulara tarihte verilen yanıtları ve bu konudaki tartışmaları ele alarak meselenin genel ve tarihsel bir tablosunu bize sunuyor. Platon, Aristoteles, Marcus Aurelius gibi Eski Yunan ve Roma düşünürlerinden Anselmus, Thomas Aquinas, Augustinus ve Yahudi-Hıristiyan geleneğine, Doğu’nun bilgelerine, İbni Rüşd, Fârâbî ve Gazzâlî gibi İslam düşünürlerinden Alvin Plantinga, Graham Oppy, Sam Harris, Richard Dawkins, Max Tegmark gibi Batılı modern ilahiyatçılara, bilim insanlarına ve Yeni Ateizm hareketine kadar uzanan bir çizgide “Tanrı var mı?” sorusuna verilen çeşitli yanıtları ve bu yanıtlara sunulan akılcı gerekçeleri ortaya koyarak soruya felsefece bir yanıt vermenin nasıl bir iş olduğunu da gösteriyor. (shrink)

Predication is a lingual relation. We have this relation when a term is said (λέγεται) of another term. This simple definition, however, is not Aristotle’s own definition. In fact, he does not define predication but attaches his almost in a new field used word κατηγορεῖσθαι to λέγεται. In a predication, something is said of another thing, or, more simply, we have ‘something of something’ (ἓν καθ᾿ ἑνὸς). (PsA. , A, 22, 83b17-18) Therefore, a relation in which two terms are posited (...) to each other in a way that one is said (predicated) of the other is a predication. The term of which the other term is said is called a subject (ὑποκειμένον) and the other, which is said about the subject, is called the predicate. Thus, in a predication the predicate is predicated of the subject; given that being predicated is almost as the same as being said. The relation between being said and being predicated is so close that ‘if something is said of a subject both its name and its definition are necessarily predicated of the subject.’ (Cat., 5, 2a19-26) This, however, is true only about the second genera and not the accidents. a) Nature of relation in predication What is Aristotle’s theory about the nature of the relation in a predication? How does he fundamentally understand this relation? Phil Corkum distinguishes between predication logic and traditional term logic and argues that the relation between subject and predicate in Aristotle is of the latter kind. While in predicate logic, subjects and predicates have distinct roles, they have the same role in traditional term logic. In predication logic, subjects refer, but predicates characterize. Thereupon, a sentence expresses a truth if the object to which the subject refers is correctly characterized by the predicate. In traditional term logic, both subjects and predicates refer and a sentences expresses a truth if both name one and the same thing. He concludes that Aristotle ‘problematically conflates prediction and identity claims’ because while he thinks both subjects and predicates refer, he would deny that a sentence is true just in case the subject and the predicate name one and the same thing. Based on this, Corkum believes that Aristotle’s core semantic is not identity but the weaker relation of constitution, which is a mereological interpretation: ‘All men are mortal’ is true just in case the mereological sum of humans is part of the mereological sum of mortals. b) Aristotle’s theory of predication: one or two theories? Frank Lewis finds an inconsistent gap between the theory of predication in the Categories and that in the later books of the Metaphysics VII, 6. So too Joan Kung, Terry Irwin, Daniel Graham. c) Distinction of ‘being said of’ and ‘being in’ Owen enumerates the texts in which Aristotle’s distinction between ‘being said of’ and ‘being in’ is asserted: OI. 11b38-12a17; To., 127b1-4; Cat. 1a20-b9; 2a11-14; 2a27-b6; 2b15-17; 3a7-32; 9b22-24 d) Predication in Aristotle and the standard ‘S is P’ Marie De Rijk Lambertus thinks that the ‘S is P’ pattern is misleading when it comes to express predication in Aristotle. In his view, ‘The Aristotelian procedure should be described in terms of appositively assigning an attribute (κατηγορούμενον) to a substrate (ὑποκείμενον), rather than ascribing a predicate to a subject by means of a copula…. The comment should be considered an attribute which is said to fall to a substrate, without understanding this procedure in terms of sentence predication.’ e) Aristotle’s predication: bipartite or tripartite? It is a difficulty to make Aristotle’s theories of name-verb predication and tripartite predication consistent. The reason is that tripartite is not consistant with his name-verb structure based on which he says that the predicate term is the ‘verb.’ (20a31; 20b1-2; 16a13-5) The problem is that in a tripartite form like ‘Socrates is white’ we cannot take ‘is white’ as the verb because, based on Aristotle himself, no part of a verb can be significant itself. (16b6-7) However, his assertions about the equivalences between the two structures (OI. 12, 21b9-10; PrA. 51b13-16; Met., 1017b22-30) must mean that they are not inconsistent in his own view. Thus, as Allen Bāck points, ‘Aristotle seems to think that he has a single, consistent theory.’ The sense of saying or speaking as the root sense of rhema makes the relation between predication (saying something of something) and verb more interesting. The use of rhema in the sense of a long expression approves this. In Plato’s work (399ac) where Socrates claims that the name anthropos derives from anthron ha opopen (‘he who examines what he has seen’) we have an onoma from, or in place of, a rhema. 1) Subject The subject (ὑποκειμένον) is that of which another term is said or predicated. Aristotle’s own definition is of a much more philosophical value: ‘By subject I mean that which is expressed by an affirmative term (λέγω δὲ ὑποκείμενον τὸ κάταφάσει δηλούμενον).’ (Met., K, 1067b18) Throughout Aristotle’s work, three kinds of subjects can be found: possible, prime and absolute subject. a) Possible subject Those things that can take the position of a subject in a predication we call possible subjects, no matter they can or cannot take the position of predicate in any predication. All terms except the ultimate predicates are possible subjects because they can take the position of subject. b) Prime subject Those that in any predication can only take the position of a subject and not the position of a predicate are prime subjects. (Cat., 5, 3a36-b2; Met., Z, 1028b36-1029a1) This is the truest sense of subject and belongs only to substances. (Met., Z, 1029a1-2) In fact, ‘that which is not predicated of a subject, but of which all else is predicated’ is a substance. (Met., Z, 1029a7-9) In Categories, besides primary substances (Cat., 2, 1b3-6), individual qualities are also said not to be able to be said of anything else. (Cat., 2, 1a23-29) Aristotle’s examples are a certain ‘knowledge-of-grammar’ (τὶς γράμματικὴ) and ‘an individual white’ (τὸ τὶ λευκὸν). Thus, although substances are indeed in the truest sense individuals and, thereby, in the truest sense primary subjects, other individuals can take the position of subject as well. c) Absolute subject While substances are prime subjects of all other things, there is still something of which substances can be predicated and this predication is not an accidental predication: matter. (Met., Z, 1029a21-24) This predication is, indeed, the predication of a ‘form or this’ on matter and material substance. (Met., Θ, 1049a34-36) The only thing that is absolutely a subject, therefore, and can be a predicate is prime matter (πρώτη ὓλη). (Met., Θ, 1049a24-27) d) Subject and substance The most important thing in being a substance is being a subject: ‘It is because the primary substances are subjects for all the other things and all the other things are predicated of them or are in them, that they are called substances most of all.’ (Cat., 5, 2b15-17) And what is nearer to this position is more a substance as a species is more a substance than a genus.’ (Cat., 5, 2b7-8) e) Primary versus accidental subject A subject is a primary subject in a predication when the predicate is predicated of it as itself. In such a case, the subject is the subject of the predicate qua itself and not qua something else. A subject, on the one hand, is an accidental subject when it is not the primary subject of the predicate that is predicated on it. It means that a subject is an accidental subject when the predicate is predicated of it not qua itself but qua something else. An accidental subject is, therefore, anything other than a substance. 2) Predicate as universal It is evident from our discussion of kinds of subjects that except matter, primary substances (if we ignore both accidental predication and cases of absolute subjects) and other individuals, everything else can take the position of a predicate. Since primary substances are individuals, it results that everything except matter and individuals are capable to take the position of predicate. The immediate consequence of this is that the predicate must be a universal. When individuals cannot take the position of predicate, this position cannot be taken by any particular. Therefore, only universals can be predicated of others. Moreover, albeit universals can be a simple subject (for another universal), they are not prime subjects. The closeness of universal and predicate is to the extent that Aristotle differentiates universal from subject. (Met., Θ, 1049a27-30) 3) Categories or classes of predicates Aristotle distinguishes ten highest classes into one of which each predicate must necessarily fall: substance (or what a thing is), quality, quantity, relation, place, time, position, state, activity and passivity. (Cat., 4, 1b25-27; To., I, 9, 103b20- ; PsA., A, 22, 83b13-23) The substance counted among predicates must refer to secondary and not primary substances not only because Aristotle insists that primary substances cannot be predicated but also from his own examples of the category of substance: man and animal. (To., I, 9, 103b25) However, if a predicate be asserted of itself or its genus be asserted of it, the predicate signifies substance or what is; but if ‘one kind of predicate is asserted of another kind,’ it signifies one of the other nines. (To., I, 9, 103b30) These categories are so comprehensive that no predicate can remain outside them so that even non-being has as many senses as categories. (Met., M, 1089a26-30) a) That whether Aristotle’s categories are merely linguistic or fundamentally ontological is a so much controversial dispute. Some like G. E. R. Lloyd believe that ‘categories are primarily intended as a classification of reality … rather than of the signifying terms themselves.’ b) Although Aristotle’s categories have been historically regarded as a classification of predications, there are some recent commentators like Jonathan Barnes that think it is classifying predicates and not predications. 4) Kinds of predicates In his introduction of Categories, as J. W. Thorp truly points out , Aristotle distinguishes between the category of substance and the other categories using μὲν ... δὲ construction. This construction illustrates that beside tenfold classification of categories, there is an even more crucial differentiation between two kinds of predicates: substance or what is on the one hand and the other nine ones on the other hand: the distinction between what is predicated of the subject as what it is and what is predicated of it as an accident. Therefore, we have three kinds of classification - a twofold, a fourfold and a tenfold-complicatedly classifying the same thing, viz. the predicate. Predicates can be divided also to four kinds: property, definition, genus and accident. (To., I, 4, 101b11-20) A property is that predicate that is convertible with its subject and does not signify its essence. A definition is that predicate that is convertible with its subject and signifies its essence. It is a genus if it is not predicated convertibly and is contained in the definition of its subject. And it is an accident if it is neither convertible nor contained in the definition of its subject. (To., I, 8, ^103b3) All of these four kinds are among categories. (To., I, 9, 103b20) It seems that there might be some kind of relation between the twofold and the fourfold distinction: whereas genus and definition are predicated as what it is, accidents are not so predicated. There seems to be some rules that determine to each of these four kinds each predicate belongs. At To., IV, 123b30ff. Aristotle asserts: ‘If B has a contrary and A does not, then B does not belong to A as its genus.’ There is a dispute around per se accidents (τὰ καθ’ αὑτὰ συμβεβηκότα) (Topics., 102a18) whether they must be regarded as either of the four kinds or as a fifth kind. Barnes (1970) argued that they ‘do not fit at all neatly into the fourfold classification.’ He argues that based on the definition of accidents at A, 5, 102b4-5, they must be accidents but based on another definition, A, 5, 102b6-7, they cannot be accidents. He also defends the view that they are not properties. Barnes concludes: ‘This shows that the two definitions are not equivalent, and hence that the ‘predicables’ are not well-defined.’ Demetris J. Hadgopoulos defends the view that the two definitions of accidents are equivalent and per se accidents are properties. 5) Five types of predications We have five kinds of predications based on our division of subjects and our discussion of predicates: simple, primary (itself divided to substantial and accident), accidental (itself divided to primary and secondary), aoincidental and absolute predication. a) Simple predication. This is a predication in which a universal is predicated of either a particular or a universal subject. This sense of predication includes all other senses except the first kind of accidental predication. b) Primary predication. This is a predication in which a universal is predicated of a primary subject, namely a substance. A primary predication is of two kinds: i) Substantial predication. A primary predication in which the predicate is part of, or is included in, the definition of the subject. The universal that is the predicate here is the definition or the genus or the species or the diferentia of the subject. It is this predication that Aristotle calls a unity: ‘A statement may be called a unity … because it exhibits a single predicate as inhering not accidentally in a single subject.’ (PsA., B, 10, 93b35-37) It is only substantial predicates that can be predicated of each other: ‘Predicates which are not substantial are not predicated of one another.’ (PsA., A, 22, 83b18-19) Aristotle defines a substantial predication also in another way. A predication in which a higher genus is predicated on a lower genus, species, a substance or an individual, (or a species is predicated on an individual) is a substantial predication. Therefore, a substantial predication is a predication in a series that has individuals on one of its ends and a general category on its other end. In fact, only substantial predicates can be predicated of one another. (PsA., A, 22, 83b17-19) This series cannot be an infinite series because otherwise not only substances would not be definable but also a genus would be equal to one of its own species. (PsA., A, 22, 83b7-10) -/- ii) Accident predication. A primary predication in which the predicate is not part of, or is not included in, the definition of its subject. The universal that is the predicate here is the property or the accident of the subject. c) Accidental predication. This is a predication in which the subject is not a primary subject and its predicate is a substance. This predication is of two kinds: i) Primary accidental predication. This is a predication in which an accident is predicated of substance. Such a predication can go ad infinitum, which is inferable from Aristotle’s assertion that the secondary accidental predication cannot go ad infinitum. ii) Secondary accidental predication. It is a predication in which an accident is predicated of another accident. Such a predication, Aristotle asserts, cannot go ad infinitum because even more than two accidents cannot be combined. Now what is the meaning of Aristotle’s assertion that we cannot continue this ad infinitum? Does it mean that we cannot continue the predication ‘The musician is white’ and say ‘The white is Athenian?’ But why not? Or maybe he means that by adding any predication, we are still in a condition of predicating two accidents of a substance on each other. -/- As primary subjects, substances can also take the position of predicate though not essentially but accidentally. In propositions like ‘the white is a log’ or ‘That big thing is a log’ we observe substance taking the position of predicate but this is only accidentally: ‘When I affirm ‘the white is a log,’ I mean that something which happens to be white is a log- not that white is the subject in which log inheres (οὐχ ὡς τὸ ὑποκείμενον τῷ ξύλῳ τὸ λευκόν ἐστι), for it was not qua white or qua a species of white that the white (thing) came to be a log (οὔτε λευκὸν ὄν οὔθ᾿ ὃπερ λευκόν τι ἐγἐνετο ξύλον), and the white (thing) is consequently not a log except incidentally.’ (PsA., 22, 83a3-9) Aristotle compares this accidental use of substance in the position of predicate with the substantial use of it in the place of a subject: ‘On the other hand, when I affirm ‘the log is white,’ I do not mean that something else, which happens to be a log, is white (οὐχ ὃτι ἓτερόν τί ἐστι λευκόν, ἐκείνῳ δὲ συμβέβηκε ξύλῳ εἶναι), (as I should if I said ‘the musician is white,’ which would mean ‘The man who happens also to be a musician is white’); on the contrary, log is here the subject- the subject which actually came to be white, and did so qua wood or qua a species of wood and qua nothing else.’ (PsA., 22, 83a8-14) Aristotle asks us not to call propositions like ‘The white is a log’ a predication at all or at least call them accidental predication instead of simple (ἁπλως) predication. (PsA., A, 22, 83a14-17) An accidental predication, in which we have a substance in the place of predicate, is different from an essential predication in that while the subject of an accidental predication is said to be the predicate not by itself but as something different with which it coincides, the subject of an essential predicate is said to be the predicate by itself and not because it is something else: ‘Since there are attributes which are predicated of a subject essentially and not accidentally- not, that is, in the sense in which we say ‘That white (thing) is a man,’ which is not the same mode of predication as when we say ‘The man is white’: the man is white not because he is something else but because he is man, but the white is man because ‘being white’ coincides with ‘humanity’ within one subject. Therefore, there are terms such as are essentially subjects of predicates. (PsA., A, 19, 81a24-29) This capability of ‘non-essentially and only accidentally’ being a subject does belong, in fact, to all sensible things. (PsA., A, 27a32-36) d) Coincidental predication. this is a predication in which none of the subject and predicate are a substance or an individual. In this predication, one of the accidents of a substance or individual is predicated of one of the other accidentals of the same substance or individual. For example, when it is said that ‘The white is musical,’ there is an individual, say Socrates, for which both of white and musical are accidents. e) Absolute predication. This is a predication in which a form or a substance is predicated of a matter or a material substance. Some commentators like Loux and Lewis regarded this predication as close to accident predication, both based on inherence. As R.M. Dancy points out, these predications make Aristotle’s theory of predication immanentist: not only accident predications are explained by the immanence of accidents in substances, some of the substantial predications, which were not explained in Categories, are also explained by the immanence of form in matter. It is interesting that in this kind of predication, it is the predicate and not the subject, which is in the strictest sense substance. As the central books of Metaphysics claim, the form is the substance. Thus, in this predication, substance gets away from the sense of ὑποκείμενον. Corkum mentiones 68a19 as the only instance where Aristotle explicitly claims that a term may be predicated of itself, a passage that is, in Corkum’s view, problematic. 6) Demonstrable predicates Those predicates are demonstrable that are so related to their subjects that there are other predicates prior to them predicable of their subjects (ἔτι δ᾿ ἄλλος, εἰ ὧν πρότερα ἄττα κατηγορεῖται). (PsA., A, 22, 83b32-34) 7) Series of predications Since it is possible for a predicate to be itself the subject of another predication, we can have a series of predications in which the predicate of a predication is the subject of the next predication. This series has the following features: a) It has a limit (in number) (PsA., A, 22, 83b14-16) on the side of subjects: there are subjects that cannot themselves be predicated (PsA., A, 27, 43a39-41), which are, as we noted, prime subjects: particulars, i.e. prime substances and other individuals. (PsA., A, 19-22) Aristotle calls them ultimate (ὓστατον). (PsA., 21, 82a36-b1) b) It has a limit (in number of kinds) (PsA., A, 22, 83b14-16) also on the side of predicates: there must be predicates that cannot be subjects. (PsA., A, 19-22; PsA., A, 27, 43a36-39) Aristotle calls them primary (πρῶτον). (PsA., A, 21, 82b1-4) These are the highest categories or the highest genera of categories. (PsA., A, 22, 83b14-16) c) The series has an escalating shape from mere subjects at its downside to mere predicates at its upside. It is Aristotle himself whos uses the words up and down in this sense. (e.g. PsA., A, 22, 83b2-3) d) The predications that lie between lowest and highest ones must be finite in number. (PsA., A, 19-22 especially: 20, 82a21-35) These have subjects and predicates, each capable of both of the roles of being subject and being predicated. A result of this fitness is that neither demonstration can go to infinity nor everything is demonstrable, the two points Aristotle always insist on. e) The upward side includes the more universal ones and the downward the more particular ones. (PsA., 20, 82a21-23) f) It follows from the above features that ‘neither the ascending nor the descending series of predications … are infinite.’ (PsA., A, 22, 83b24-25) g) Reciprocation and convertibility. Except in case of terms (i.e. subjects and predicates) that are at each of the ends of series of predications, namely ultimates and primaries, it is possible to reciprocate (ἀντιστρέφειν) terms and convert the predication. (PsA., A, 19, 82a15-20) h) Antipredication. Antipredication means that in a predication (S is P), the subject becomes the predicate of its predicate (P is S) in the same category its predicate was predicated on it. For example, if P is in the category of quality, antipredication means that S be predicated of P in the category of quality. In other words, P is a quality of S and S is a quality of P. Aristotle rejects this. (PsA., A, 22, 83a36-b3) i) Self-predication versus other-predication. Aristotle distinguishes between a predication in which a term is said of itself and a predication in which a term is said of another. (Phy., Δ, 2, 209a31-33) j) Predicablity (Cat., 5, 3a36-b2): 1) Primary substances and individuals are not predicable. 2) Secondary substances are of two kinds: genus and species i) Genus is predicable able both of the species and of the individuals. ii) Species is predicable of the individual. 3) Differentiae are predicable both of the species and of the individuals. 8) Predication as classification a) Richard Patterson believes that Aristotle’s so repeated construction using hoper (estin A hoper B) in Topics (120a23 sq., 122b19, 26sq., 123a, 124a18, 125a29, 126a21, 128a35. Also in Posterior Analytics (83a24-30) (Brunschwig’s list. ‘expresses the fact that A is a kind of B (esti A B tis), that A is a species of the genus B.’ 9) Universal predication Aristotle defines universal predication (κατὰ παντὸς κατηγορεῖσθαι) as such: ‘wherever no instance of the subject (τῶν τοῦ ὑποκειμέμνου) can be found of which the other term cannot be asserted.’ (PrA., A, 24b27-29) In this predication, the subject is included in another as in a whole (ἐν ὃλῳ εἶναι) and the predicate is predicated of all of the subject (κατὰ παντὸς κατηγορεῖσθαι). (PrA., A, 24b26-27) Attach another discussion we had about ἐν ὃλῳ here. 10) Quantity of predication A predication, truly stated, has a quantity, which is the number of objects under the name of the subject of which the predicate is predicated. The quantity of subject can be stated in four ways: a. Indefinite: when the predicate belongs or does not belong to the subject without any mark to show to haw many of the particulars under the name of the subject it does or does not belong. E.g. ‘Man is white’; ‘Man is not white.’ (PrA., A, 24a20; OI., I, 7, 17b8-12) b. Universal quantity: When the predicate belongs to all or none of the subject. E.g. ‘Every man is animal’; ‘No man is animal.’ (PrA., A, 24a18-19; OI., I, 7, 17b5-6) The contrary of a predication of a universal quality is a predication of a universal quality. E.g. the contrary of ‘Every man is white’ is ‘No man is white.’ (OI., I, 7, 17b20-23) c. Particular quantity: When the predicate belongs (or does not belong) to some of the subject. E.g. ‘Some men are white’; ‘Some men are not white.’ (PrA., A, 24a19-20) d. Single quantity: when the subject is a proper name of only one object. E.g. ‘Socrates is white’; ‘Socrates is not white.’ The contrary of this predication is of a single quantity: ‘Socrates is not white.’ (OI., I, 7, 17b38-18a4) 11) Convertibility of predication. Some predications are convertible, that is, it is possible to change the place of subject and predicate in a true proposition so that the converted proposition remains true. This is supposed to mean that given the truth of a predication, the truth of the converted predication is inferable. The convert form of a predication depends on its quantity. a. Indefinite quantity: This predication has no strictly true convert because its quantity is not stated. b. Universal quantity: It can be converted in two ways: i) A negative universal can be converted to a negative universal in which the terms are changed. E.g. ‘No pleasure is good’ can be converted to ‘No good is pleasure.’ (PrA., A, 2, 25a5-8 and a14-19) ii) An affirmative universal can be converted to an affirmative particular in which the terms are changed. E.g. ‘Every pleasure is good’ can be converted to ‘Some good is pleasure.’ (PrA., A, 2, 25a7-9) c. Particular quantity: If it is negative, it cannot be converted but if it is affirmative, it can be converted to an affirmative predication with particular quantity. E.g. ‘Some pleasure is good’ can be converted to ‘Some good is pleasure.’ (PrA., A, 2, 25a10-13 and a20-24) d. Single quantity: It cannot be converted. 12) Characteristics of relations between subject and predicate 1. A predicate is of a wider range than its subject. It is based on this fact that Aristotle: a) Prevents individuals to be predicate because there is nothing of which an individual be of a wider range. In other words, it is due to the fact that since an individual is only ‘one particular’ thing and, thus, cannot be of a wider extent than anything that Aristotle prevents them of being a predicate. Matthews, however, thinks we cannot use Socrates, a substance and an individual, in the place of predicate and say it of Socrates because ‘Socrates does not classify Socrates: it names him.’ b) Prevents differentia, species and things under species to be predicated of genus. (To., Z, 6, 144a27-) c) Prevents the species and the things under it to be predicated of the differentia. (To., Z, 6, 144b1-4) d) Also about the effect because it is wider than its subject. (PsA., B, 17, 99a) e) Each attribute is wider than every individual it is predicated on, though several attributes, collectively considered, might not be wider but exactly the substance of a thing. (PsA., B, 13, 96a32-b1) 2. The predicate of a predicate of a subject will be predicated of the subject too: ‘whenever one thing is predicated of another as of a subject, all things said of what is predicated will be said of the subject too.’ (Cat., 3, 1b10-15) In fact, it is due to its predication of the subject that it is predicated of its predicate. (Cat., 5, 2a36-b1) Moreover, what is not predicated of the predicate of a subject cannot be predicated of it as well. (PrA., A, 27, 43b22-27) Thus, what, for example, is not predicated of animal, cannot be predicated of man. 3. The predicate of a subject can be predicated of its predicates as well. (Cat., 5, 3a1-6) For example, you call the individual man grammatical and, thence, you call both a man and an animal grammatical. Nonetheless, the predicate of a subject belongs to it more properly than to its higher predicates. (PrA., A, 27, 43a27-32) 4. It is only the subject that can be distributed and not the predicate. (PrA., A, 27, 43b16-22; OI, I, 7, 17b12-16) Therefore, we can say e.g. ‘Every man is animal’ but we cannot say ‘Every man is every animal.’ 5. It is the reason of the relation between subjects and predicates, that is the reason of predication, which is the subject of inquiry. (Met., Z, 1041a20-24) In other words, since it is a meaningless inquiry to ask why a thing is itself (Met., Z, 1041a14-15), the only remaining meaningful inquiry is to ask why something is something else, i.e. to ask about the reason of predication. 6. A subject cannot categorize its predicate in the same category in which it is categorized by it. If e.g. A is a quality of B, B cannot be a quality of A. Therefore, there is no reciprocation in the same category. (PsA., A, 22, 83a36-39) 13) Characteristics of series of predications 1. A series of secondary accidental predication cannot go ad infinitum for not even more than two terms can be comnbined. For an accident is not an accident of an accident, unless it be because both are accidents of the same subject. (Met., Γ, 1007b1-4) 2. Infinite series cannot be traversed in thought. (PsA., A, 22, 83b6-7) 3. The predications of genera on each other must be ended and cannot go to infinity because otherwise not only substances would not be definable but also a genus would be equal to one of its own species. (PsA., A, 22, 83b7-10) Therefore, a series of predication of genera on each other must be limited on both sides. There must be an upward limit in general categories as well as a downward limit in individual because they cannot be predicated of others. Whatever lies between these limits can both be predicated of others and others be predicated of them. (PrA., A, 27, 43a36-43) 4. The order of predicates matters: it makes a difference whether the series be ABC or BAC. (PsA., B, 13, 96b25-32) . (shrink)

A collection of papers presented at the First International Summer Institute in Cognitive Science, University at Buffalo, July 1994, including the following papers: ** Topological Foundations of Cognitive Science, Barry Smith ** The Bounds of Axiomatisation, Graham White ** Rethinking Boundaries, Wojciech Zelaniec ** Sheaf Mereology and Space Cognition, Jean Petitot ** A Mereotopological Definition of 'Point', Carola Eschenbach ** Discreteness, Finiteness, and the Structure of Topological Spaces, Christopher Habel ** Mass Reference and the Geometry of Solids, Almerindo E. (...) Ojeda ** Defining a 'Doughnut' Made Difficult, N .M. Gotts ** A Theory of Spatial Regions with Indeterminate Boundaries, A.G. Cohn and N.M. Gotts ** Mereotopological Construction of Time from Events, Fabio Pianesi and Achille C. Varzi ** Computational Mereology: A Study of Part-of Relations for Multi-media Indexing, Wlodek Zadrozny and Michelle Kim. (shrink)

In contrast to the opinion of numerous authors (e.g. R. Rudner, P. Kitcher, L. R. Graham, M. Dummett, N. Chomsky, R. Lewontin, etc.) it is argued here that the formation of opinion in science should be greatly insulated from political considerations. Special attention is devoted to the view that methodological standards for evaluation of scientific theories ought to vary according to the envisaged political uses of these theories.

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)

A. Accident 1. We call an accident (συμβεβηκὸς) that which attaches to something and can be truly asserted, but neither of necessity nor usually.’ (Met. , Δ, 1025a14-16) 2. Whenever an accident attaches to a subject, it attaches to it not because it is that subject (μὴ διότι τοδὶ ἧν). (Met., Δ, 1025a21-24) 3. ‘There is no definite cause for an accident, but a chance cause, i.e. an indefinite one.’ (Met., Δ, 1025a24-25) 4. ‘The accident has happened or exists, -not (...) in virtue of itself, however, but of something else. (Met., Δ, 1025a28-29) 5. ‘What attaches to each thing in virtue of itself but is not in its substance is an accident.’ (Met., Δ, 1025a30-32) 6. ‘An accident is something which, though it is … neither a definition nor a property nor a genus, yet belongs to the thing.’ (To., I, 5, 102b4-) 7. An accident is ‘something which may either belong or not belong to any one and the self-same thing, as (e.g.) being seated may belong or not belong to some self-same thing.’ (To., I, 5, 102b4-) 8. ‘There is nothing to prevent an accident from becoming a temporary or relative property … [and] there is nothing to prevent an accident from becoming both a relative and a temporary property; but a property absolutely it will never be.’ Aristotle’s example is ‘being seated.’ That it is a temporary property is evident. It is also a relative property to those who are not seating when he is the only person sitting. Therefore, it is a temporary and also a relative property. 9. ‘In the case of accidents and in no other it is possible for something to be true in a certain respect and not universally’ and ‘there is nothing to prevent an attribute belonging in part’ so that it is open to dispute accidents e.g. being white or just about a man because he might be white or just in part only. Thus, ‘conversion is not a necessary process in the case of accidents.’ (To., B, 1, 109a9-) B. Essential versus accidental Aristotle distinguishes between two senses of being (τὸ ὄν): accidental sense (κατὰ συμβεβηκός) and essential sense (καθ᾿ αὑτό). The accidental sense happens when something is said to be another thing while there is in fact a third thing which is both of them. Thus, being the first thing is not by itself the second thing. a) Aristotle speaks of three ways in which one thing is said in an accidental sense to be another. (Met., Δ, 1017a8-22) i) When both the subject and the predicate are accidents of a third thing and it is in fact the third thing which ‘is’ by its own. Thus, when it is said e.g. that ‘The just is musical’ it is said accidentally because it is in fact a third thing, Socrates for example, which is just and musical. (Met., Δ, 1017a13-19) ii) When that to which the attribute belongs is. The example of this must be ‘the man is musical’ because it is in fact the man which is. iii) When the subject which has as an attribute that of which it is itself predicated, itself is. The example of this must be Aristotle’s third example: ‘The musical is man.’ b) Aristotle rejects the essential sense to categories: ‘Those things are said in their own right to be that are indicated by the figures of predication; for the senses of ‘being’ are just as many as these figures.’ (Met., Δ, 1017a22-24) Aristotle does not give us any example of the essential sense. Daniel W. Graham suggests that while essential predication is of the logical form of ‘S is P,’ the logical form of the accidental predication is ‘S has P.’ Although he concedes that the is/has contrast is not Aristotle’s, for which he thinks Aristotle prefers ‘said of’/’in’ terminology, he points to the discussion of ‘have’ in Cat. 15 as an evidence of its potential value for an analysis of predication. Kirwan analyses the distinction of essential and accidental predicate as such: while essential predicates ‘are identical with the subjects of which they are predicated; other predications are true in virtue of the fact that two distinct items, e.g. a substance and a quality, ‘coincide.’ Herman Weidemann believes ‘what divides a predicative statement which predicates essentially from a predicative statement which predicates accidentally is the fact that the former does- whereas the latter does not- answer the question what its subject cannot fail to be without ceasing to exist, as the somewhat its subject goes on existing, no matter what happens to be true of it during its existence, or, what kind of things its subject must be in order to be identifiable as one and the same object as long as it exists.’ C. Essential 1. Either the formula or the name of the subject of an essential attribute is involved in it. For example, animal is involved in female but not in white. (Met., Z, 1030b23-26) 2. Essential attributes, combined together, form a unity. Thus, e.g. animal and biped form a unity because they are both essential of man. (OI., II, 11, 21a14-16) 3. Aristotle distinguishes between two kinds of essential attributes (PsA., A, 4, 73a34-b3; 22, 84a12-17): a) Those attributes that belong to their subject as elements in its essential nature as e.g. line belongs to triangle or point to line. Here the very being of triangle is composed of line or that of line is composed of points: line is contained in the formula of triangle and point in that of line. b) Those attributes whose subjects are contained in their own defining formula as e.g. straight is an essential attribute of line because line is part of the defining formula of straight or odd belongs to number because number is part of the defining formula of odd. Every attribute that is related in neither of these two ways to its subject, it is not an essential but an accidental attribute. (PsA., A, 4, 73b3-5) 4. That attribute which is not predicated of a subject other than itself is an essential attribute. A substance cannot be predicated of anything but itself and is, thus, essential. (PsA., A, 4, 73b5-10) 5. A thing consequently co-stated with anything is essential. For example, if a beast dies when its throat is being cut, its death is also essentially connected with the cutting because the cutting was the cause of death, not death a coincidence of cutting. (PsA., A, 4, 73b10-15) 6. Essential attributes in both of this sense, either in the sense that their subjects are contained in them or in the sense that they are contained in their subjects, are necessary as well as consequently co-stated with their subjects. The reason is that it is impossible for them to inhere in their subjects either simply or in the qualified sense (that one or other of a pair of opposites must inhere in the subject as e.g. one of straight or curve must be necessarily predicable of a line or one of odd or even of number). (PsA., A, 4, 73b16-21; 6, 74b5-12; B, 96b1-5) 7. Only those attributes that are within a genus are essential and possessed by their respective subjects as such and, thus, are necessary. Thereupon, both the conclusion and the premises of demonstrations which produce scientific knowledge are essential. (PsA., A, 6, 75a28-31) Therefore, ‘the extreme and the middle terms must be drawn from the same genus; otherwise, as predicated, they will not be essential and will thus be accidents.’ (PsA., A, 6, 75b10-12) Also, the theorems of a science can be demonstrated by means of another science only when they are related as subordinate to superior. (PsA., A, 6, 75b13-) 8. Our knowledge of the connexion of an attribute with a subject is essential only when ‘we know that connexion through the middle term in virtue of which it inheres (καθ᾿ὃ ὑπἀρχει), and as an inference from basic premises essential and ‘appropriate’ to the subject.’ The essential belonging of the middle to the minor has a necessary connexion with its belonging to the same genus of the major and minor: ‘If that middle term also belongs essentially to the minor, the middle must belong to the same genus as the major and minor terms (ἀνάγκη τὸ μέσον ἐν τῇ αὐτῇ συγγενείᾳ εἶναι). (PsA., A, 9, 76a4-9) 9. In an essential predication, the predicate is signified of a subject identical with itself or with a species of itself. Since only predicates which signify substance signify that the subject is identical with the predicate or with a species of the predicate, predicates signifying substance are essentially predicated and any other predicate is accidental or coincidental. Thus, while animal is essentially predicated of man because man is identical with a species of animal, white is accidentally predicated of man because man is neither identical with white nor a species of it. (PsA., A, 22, 83a24-32) Weidemann discusses the confusion between essential predications and statements of identity. He warns that the expression ‘(to be) just what a man is’ (analogous to the Greek phrase ‘(εἶναι) ὃπερ ἀνθρώπον) ought not to be confused with the expression ‘just what it is for a man to be,’ which renders the phrase τὸ ὃπερ ἀνθρώπῳ εἶναι’ (1007a22, 23, 27-28); a confusion Kirwan discusses. 10. ‘Demonstration proves the inherence of essential attributes in things.’ (PsA., A, 22, 84a11-12) 11. ‘Nothing which does not happen to belong to the genus is essentially the genus; e.g. a white man is not essentially a color.’ Thus, while justice falls within the genus, a just man does not. (To., Γ, 1, ^116a24-) 12. There is no syllogism of essence (ti esti). Nevertheless, we come to know ti esti through a demonstration. (93b15-20; cf. 93b25-28) D. Accidental 1. An accidental attribute cannot be predicated of a subject universally. Thus, we cannot say ‘Every man is musical.’ The reason is that ‘universal attributes belong to things in virtue of their nature.’ Therefore, accidental predicates are predicated only of the individuals. (Met., Δ, 1017b33-1018a2) 2. An accidental is a mere name. (Met., E, 1026b13-) 3. An accidental is obviously akin to non-being. (Met., E, 1026b21) 4. ‘That which is neither always nor for the most part we call accidental.’ (Met., E, 1026b27-33) 5. The matter (ὕλη) is the cause of the accidental because it is matter which is capable of being otherwise than as it for the most part is. (Met., E, 1027a13-16) In fact, there is cause or principle of the incidental of the same kind as there are of the essential because if there were, everything would be of necessity. (Met., K, 1065a6-8) The causes of accidental are unordered and indefinite. (Met., K, 1065a25-26) 6. Since all science is either of that which is always or of that which is for the most part, there is no science of the accidental. (Met., E, 1027a19-24; K, 1064b30-1065a6) Therefore, since an accident may also not inhere and, thus, it is impossible to prove its inherence as a necessary conclusion, there is no demonstrative knowledge of accidents. (PsA., A, 6, 75a18-23) 7. The accidental is not necessary but indeterminate. (Met., K, 1065a24-26) 8. The co-positing of a subject and a predicate which are accidental either to the same subject or to one another, whiteness and being musical for instance, does not form a unity. (OI, II, 11, 21a7-14) 9. Negative predicates, i.e. predicates including a ‘not,’ are accidental predicates. Thus, if good be an essential predicate of a subject, ‘not bad’ cannot be essential but is accidental. (OI., II, 14, 23b15-20) 10. Every attribute which does not belong to its subject in either of two senses of essential attribute (cf. PsA., A, 4, 73a34-b3), namely, belonging to their subjects as an element of its formula or their subjects belonging to them as an element of them, is an accidental attribute. (PsA., A, 4, 73b3-5) 11. Those attributes that are predicated of a subject other than themselves are accidental attributes. Thus, everything except substance is an accidental in this sense. (PsA., A, 4, 73b5-10) 12. A thing not consequentially connected with anything is accidental. For example, in ‘while he was walking it lightened,’ the lightening was not due to his walking but was a coincidence. (PsA., A, 4, 73b10-15) 13. Those attributes that are not within a genus are accidental attributes. (PsA., A, 6, 75a28-31) Therefore, the extreme and middle terms that are not drawn from the same genus are accidents. (PsA., A, 6, 75b10-12) Moreover, to apply an attribute to subjects in different genera afford knowledge of the attribute, only as inhering accidentally, not as belonging to its subject as such.’ (PsA., A, 9, 75b38-76a3) . (shrink)

Aristotle’s analysis of language is, firstly, on the basis of co-positing and positing away: this is the starting point of analysis: what is asserted in language either involves a co-positing or does not (Cat. , 2, 1a16-17). Although he does not explain what he means by co-positing, we can see that he considers something like a sentence (his examples: man runs, man wins) and not merely a co-positing of two words like not-man, which he calls an indefinite noun (OI., 2, (...) 16a30-32). Aristotle and his contemporaries had no word for ‘word.’ The closest words for ‘word’ are ὄνομα and λόγος. ὄνομα is distinguished from ῥῆμα (verb) and, thus, cannot mean word. λόγος means a sentence or statement. Daniel W. Graham (Aristotle’s Two Systems, 1987, Oxford University Press, 38, fn.27) renders λεγομενον as ‘word.’ The problem with this suggestion is that, as Aristotle asserts in Categories, it is used both for single words and the composition of several words and even sentences. Aristotle distinguishes a noun from all the followings: a) A co-positing of words: noun is a word that is said without co-positing. (Cat., 2, 1a16-19) b) Inarticulate sounds: the sounds like those that brutes produce are not considered as nouns, though Aristotle believes that they are significant. (OI., 2, 16a28-29) c) Verbs: words that carry with them the notion of time. (OI., 2, 16b6-8) So far, a noun is a word said without co-positing, without the notion of time and distinguished from inarticulate sounds. What remains in language, however, is not necessarily a proper noun, though it is related with noun. What remain are different kinds of names: 1) Noun (ὄνομα) or definite noun: a sound that is significant by convention and of which no part is significant from the rest (OI., I, 1, 16a19-20) unless not having an independent meaning, the parts contribute to the meaning of the whole (OI., I, 1, 16a22-27). This latter condition is indeed a division made by Aristotle between two kinds of nouns: a. Simple nouns: a word in which the part is in no way significant. b. Composite nouns: a word in which though the part may be significant, i) it contribute to the meaning of the whole and ii) it does not have an independent meaning. 2) Indefinite noun: expressions like ‘not-man’ that i) have no recognized term by which denote the expression and ii) are not a sentence or denial by themselves (OI, 2, 16a28-29; 10, 19b8-10). 3) Cases of a noun. This is what used in languages like Greek language that have different cases. They show the senses that are asserted by other elements like prepositions in languages like English in a form or case of the name. Thus, e.g. Φίλωνος means ‘of Philo’ while Φίλωνι means ‘to Philo’. The cases of a noun have the same definition as the noun itself. However, they are not able to combine with any of the different tenses of the verb ‘is’ so that a true or false preposition results. (OI., 2, 16ab4-5). Aristotle thinks convention (συνθήκην) is the basis of the formation of nouns: ‘The limitation ‘by convention’ was introduced because nothing is by nature a noun- it is only so when it becomes a symbol.’ (OI., I, 1, 16a27-28) In Greek language, Francesco Ademollo notes (B508, 34), onoma has a close etymological connection with any transitive verb. Thus, it seems that an onoma is essentially ‘an expression that names or refers to something. It is strange that Aristotle does not distinguish proper from improper noun. We find no text in which Aristotle made such a distinction. In fact, it seems nouns are essentially improper for him: ‘A name, e.g. ‘round,’ means vaguely a sort of whole: its definition analyses this into its particular senses. Similarly, a child begins by calling all men ‘father’ and all women ‘mother’ but later on distinguishing each of them.’ (Phy., A, 1) Nouns necessarily are applicable to others: ‘If one were defining you, he would say ‘an animal which is lean’ or ‘white’ or something else which will apply to someone other than you.’ (Met., Z, 1040a12-14) -/- . (shrink)

The following are the characteristics of a genus: 1. Those to which the same figure of predication applies are one in genus. (Met. , Δ, 1016b32-35) 2. Things that are one in genus are all one by analogy while things that are one by analogy are not all one in genus. (Met, Δ, 1016b35-1017a3) 3. A genus includes contraries. (Met., Δ, 1018a25-31) 4. All the intermediates are in the same genus as one another and as the things they stand between. (...) (Met., I, 1057a18-30; 1057b31-34) 5. Not every predicate is a genus of what it is predicated on; for this would equate a genus with one of its own species. (PsA., A, 22, 83b7-10) 6. The opposite of the genus should always be the genus of the opposite. (To., Δ, 4, ^125a27-29) 7. A genus divides the object from other things. (To., Z, 3, 140a^24) 8. None of unity and being is a genus. (Met., B, 998b22-27; Met., K, 1059b31-34; PsA., B, 7, 92b12-14) 9. There is no necessity or even no possibility that things that are the same specifically or generically should be numerically the same. (To., H, I, 152b30-) 10. To be called one due to having one genus is in a way similar to be one due to having the same matter. (Met., Δ, 1016a24-28) 11. The substance of a thing involves its genus, and thereby all the higher genera are predicated of the lower. (To., Z, 5, 143a^20- ) 12. Being falls immediately into genera. (Met., Γ, 1004a4-6) A. Characteristics of relations between genera The characteristics of relations between genera, the relations between genera and species excluded, are as follows: 1. Genus is not an element in the composition of things. (Met., I, 1057b20-22) 2. Things resulting from the same division of the same genus are simultaneous by nature. (Cat., 13, 15a3-4) 3. Processes of proof cannot pass from one genus to another. (PsA., A, 23, 84b14-18) 4. It is not necessary for subordinate genera to have different accounts. (To., I, 15, ^107a19-) E.g. when we say a raven is a bird, we also say it is a certain kind of animal. 5. It is necessary for genera that are not subordinate one to the other to have different accounts. (To., I, 15, ^107a27-30) E.g. whenever we call a thing an engine, we do not call it an animal, nor vice versa. 6. If one of the genera is predicated in what it is, all of them, both higher and lower than this one, if predicated at all of the species, will be predicated of it in what it is; so that what has been given as genus is also predicated in what it is. (To., Δ, 2, ^122a10) 7. The same object cannot occur in two genera of which neither contains the other. (To., Z, 139b32-140a2) 8. Those to which the same figure (σχῆμα) of predication applies, are the same in genus. (Met., Δ, 1016b32-35) 9. Attributes that inhere always in each several things can be divided to two groups: those that are wider in extent but not wider than its genus and those wider than its genus. (PsA., B, 13, 96a24-27) 10. The relation between A and B must be extendable in respect of all the genera of A. Thus, if A is double of B, it must also be in excess, the genus of double, to B. Aristotle accepts, however, that this may be objectable in some cases: while knowledge is called knowledge of an object of knowledge, it cannot be called a state and disposition (which is the genus of knowledge) of an object of knowledge. In fact, it is a state and disposition of the soul. (To., Δ, 4, 124b28-34) B. Characteristics of species The following are the characteristics of species: 1. Things are said to be other in species if they are of the same genus but are not subordinate the one to the other. (Met., Δ, 1018a38-b2; Met., I, 1057b35-37) 2. Contraries are other than one another in species. (Met., Δ, 1018b5-7; Met., I, 1058b26-) 3. It is not sufficient for a difference to be the basis of distinguishing species in a genus because it belongs to the genus in virtue of its nature as, e.g., the difference between men and women belongs to animal in virtue of its nature. It must also be a modification peculiar to the genus (οἰκεῖα πάθη τοῦ γένους) in the strongest sense. (Met., I, 1058a29-37) Thus, contraries which are in the formula (ἐν τῷ λόγῳ) make a difference in species, but those which are in the compound material thing do not make one as e.g. being male and female is a difference in matter. (Met., I, 1058a37-b23) 4. Some things are peculiar to the species as distinct from genus: there are attributes peculiar to each distinct species. (PrA., A, 27, 43b27-29) 5. There is no necessity or even no possibility that things that are the same specifically should be the same numerically. (To., H, I, 155b30-) C. Characteristics of relations between genera and species The following are the characteristics of relations between genera and their species: 1. Although species predicated of individuals seem to be principles rather than the genera, it is hard to say, Aristotle asserts, in what sense species are to be taken as principles. (Met., B, 999a14-21) 2. Things that are one in species are all one in genus, while things that are one in genus are not all one in species. (Met., Δ, 1016b35a1) 3. The relation of a species to its genus is like the relation of primary substance to all others: the species is a subject for the genus (ὑπόκειται γὰρ τὸ εἴδος τῷ γένει) and the genera are predicated of the species but the species are not predicated of them. (Cat., 5, 2b17-22) 4. Of the species themselves- those which are not genera- one is no more a substance than another: a certain horse is no more a substance than another horse. (Cat., 5, 2b22-26) 5. Genera are prior to species since they do not reciprocate as to implication of existence (κατὰ τὴν τοῦ εἶναι ἀκολούθησιν). For example, if there is a fish there is an animal, but if there is an animal there is not necessarily a fish. (Cat., 13, 15a4-7) 6. What belongs both to a species and to its genus, it belongs to the species more properly indeed than to the genus. (PrA., A, 27, 43b29-32) 7. A predicate drawn from the genus is never ascribed to the species in a derived form and as its genus. Thus, e.g. coloured cannot be a genus of ‘white’ when we say ‘white is coloured.’ (To., B, I, ^109b1-5) 8. Genera are predicated of their species synonymously because the species take on both the name and the account of their genera. (To., B, I, ^109b3-6) 9. All the attributes that belong to the species belong to the genus as well but there is no necessity that all the attributes that belong to the genus should belong also to the species. (To., B, 4, 111a20-32) 10. Those things of which the genus is predicated must also of necessity have one of its species predicated of them. (To., B, 4, 111a33-) 11. The higher genus should be predicated of the species in what it is. (To., Δ, 2, ^122a6) 12. The species, or any of the things which are under the species, is not predicated of the genus because the genus is the term with the widest range of all. (To., Z, 6, 144a27f.) 13. The same species cannot be in two genera neither of which contains the other. (To., Z, 6, 144b14f.) 14. None of the species of a genus is prior or posterior to other species but they are thought to be simultaneous by nature. (Cat., 13, 14b38-15a1) 15. Daniel W. Graham points that sometimes Aristotle speaks of species as classes (Cat., 5, 2a14-17) and sometimes as properties or a certain character (ποιόν τι) of substances, which is difficult to be distinguished from the category of quality. (Cat., 3b13-22) D. Characteristics of differentia 1. The last differentia will be the substance, the definition and the form of the thing. (Met., Z, 1038a18-28) 2. If we divide according to accidental qualities, there will be as many differentiae as there are processes of division. (Met., Z, 1038a25-28) 3. The differentia divides the object from any of the things contained in the same genus. (To., Z, 3, 140a24-) 4. A. C. Lloyd argues that Aristotle’s logic of classification contains a vicious circle because: ‘For a genus to be predicated unequivocally and essentially of a species the specific differentiae have to be ‘appropriate’; but in order to know whether a proposed differentia is appropriate we have to know whether the genus is predicable essentially of the species thus defined.’ The predication of differentia on primary substance seems to make difficulties in Aristotle’s system, as Terence Irwin points out. It seems to violate the distinction of strong predication and inherence, a distinction between predication of count-nouns and predication of characterizing adjectives. Irwin says that this violation is only apparent because although the differentia-term is an adjective, its gender agrees with the gender of the understood genus-term and not with that of the subject term. ‘Man is biped’ is indeed ‘Man is a biped animal.’ This shows, Irwin asserts, ‘why Aristotle can still mention that strong predication is nominal and inherence is adjectival.’ Differentiae are not, however, secondary substances, as Aristotle himself insists. A differentia does not say what the thing is, as secondary substances do, but only what it is like or what sort it is. (ποιον: To., 122b12-17; 128a20-29; 139a28-31; 142b25-29) Nonetheless, differentiae are not qualities because they are not inherent. Thus, they cannot be regarded in any of the ten categories. Irwin thinks that this anomaly is unnecessary because Aristotle could give good reasons for taking differentiae to be second substances. E. Characteristics of relations between differentia and genera or species 1. It is not possible for the genus to be predicated of the differentia taken apart from the species. (Met., B, 998b23-25; Met., K, 1059b31-33; To., VI, 6, 144a32-b1) 2. It is not possible for the species of the genus to be predicated of the proper differentiae of the genus. (Met., B, 998b24-26) 3. Where the differentia is present, the genus accompanies it, but where the genus is, the differentia is not always present. (Met., Δ, 1014b12-14) 4. The number of species are equal to the number of differentiae. (Met., Z, 1038a15-18) 5. The differentiae of genera which are different and not subordinate one to the other are themselves different in kind. (Cat., 3, 1b16-20; To., I, 15, ^107b19-) 6. There is nothing to prevent genera subordinate one to the other from having the same differentia. (Cat., 3, 1b20-22) 7. Since the higher genera are predicated of the genera below them, all differentiae of the predicated genus will be differentia of the subject also. (Cat., 3, 1b21-24) 8. The definition of the differentia is predicated of that of which the differentia is said. (Cat., 5, 3a25-28) 9. In giving what a thing is it is more fitting to state the genus than the differentia. For example, anyone who says that man is an animal shows what man is better than who describes him as terrestrial. (To., Δ, 6, ^128a24-27) 10. The differentia always signifies a quality of the genus, but the genus does not do this of the differentia. (To., Δ, 6, 128a27-29; To., Z, 6, 144a20-23) 11. A specific differentia, along with the genus, always makes a species. (To., Z, 6, 143b^1-) 12. A genus is always divided by the differentiae that are co-ordinate with it in a division and the differentiae that are co-ordinate in a division are all true of the genus. (To., Z, 6, 143b^1-) 13. Differentia cannot be predicated of the genus because genus is the term with the wider range. (To., Z, 6, 144a27-) In fact, genus is predicated, not of the differentia, but of the object of which the differentia is predicated. (To., Z, 6, 144a^31-b3) 14. Neither species nor the objects under it can be predicated of the differentia because the differentia is a term with a wider range than the species. (To., Z, 6, 144b4-) 15. The differentia is posterior to genus but prior to the species. (To., Z, 6, 144b^9-) 16. The same differentia cannot be used of two genera neither of which contains the other and if they do not both fall under the same genus. Otherwise, the same species will be in two genera neither of which contains the other, which is impossible. (To., Z, 6, 144b14-) 17. Genus and differentia are prior to and more familiar than the species: ‘For annul the genus and the differentia; and the species too is annulled, so that they are prior to the species. They are also more familiar; for if the species is known, the genus and differentia must of necessity be known as well (for anyone who knows what a man is knows also what animal and terrestrial are), whereas if the genus or the differentia is known it does not follow of necessity that the species is known as well; thus the species is less intelligible.’ (To., Z, 4, 141b15-) F. Characteristics of relations in series of classes 1. Mutually exclusive series. If no term in the series ACD… is predicable of any term in the series BEF…, and if G- a term in the former series- is the genus of A, clearly G will not be the genus of B; since, if it were, the series would not be mutually exclusive. (PsA., A, 15, 79b6-11) 2. Atomic disconnection of series. Of two mutually exclusive series ACD and BEF, if neither A nor B has a genus and A does not inhere in B, this disconnection must be atomic. (PsA., A, 15, 79b6-14) G. Characteristics of relations of individuals 1. No individual in a species is more substance than another individual in another species. (Cat., 5, 2b26-28) An individual man, for instance, is no more a substance than an individual ox. 2. Each attribute is wider than every individual it is predicated on, though several attributes, collectively considered, might not be wider but exactly the substance of a thing. (PsA., B, 13, 96a32-b1) 3. Not distinguishing between class membership and class inclusion? Some commentators like Vlastos and Ackrill (1963, 76) criticized Aristotle because he, they believe, did not distinguish between class membership (between species and particulars) and class inclusion (between genera and their species). Having accepted this point, Daniel W. Graham believes it is ‘question-begging in a curious way.’ Phil Corkum thinks that Aristotle employs mereological notions. (This criticism seems so strange because all the Aristotle’s point in distinguishing species 2 from genera is strictly the distinction of class membership and class inclusion as they call them so. (shrink)

When is a testimony-based belief justified? According to so-called "Anti-Reductionism," the principle that a hearer is prima facie justified to take what another tells them at face value is true. I call this position "Liberal Foundationalism." I call it "liberal" for it is more liberal than "Moderate Foundationalism" that holds that perception-based beliefs are prima facie justified but testimony-based beliefs are not. Liberal Foundationalism has two interpretations: the principle is a contingent empirical truth, or an a priori necessary truth. I (...) call the view that the principle is a priori necessary "Liberal Fundamentalism." This chapter defends Liberal Fundamentalism against objections in the first half, and then in the second half it introduces "Weak Liberal Fundamentalism," the view that it is a priori necessary that testimony provides some epistemic support, but perhaps not enough, absent defeat, for knowledge. In later work I abandon the view that the principle is a priori necessary, but I still maintain the distinction between Strong and Weak variants of the principle, and the replies to many of the objections to the principle. (shrink)

Hylomorphism is the Aristotelian theory according to which objects are composites of form and matter. Form is what unifies the various parts of an object – the matter – into a cohesive whole. Some contemporary hylomorphists argue their theory applies beyond the realm of concreta, and that it explains the unity of various abstract entities. Not everyone agrees. Recent criticism alleges that hylomorphism fails to explain the unity of certain abstract entities, namely, complex properties – properties with other properties as (...) proper parts. Here, I both respond to this criticism and show that and how hylomorphism extends to the domain of complex properties. By discussing hylomorphism’s applicability to the hitherto unchartered domain of complex properties, I hope to defend its credentials as a general mereological theory. (shrink)

Context: At present, we lack a common understanding of both the process of cognition in living organisms and the construction of knowledge in embodied, embedded cognizing agents in general, including future artifactual cognitive agents under development, such as cognitive robots and softbots. Purpose: This paper aims to show how the info-computational approach (IC) can reinforce constructivist ideas about the nature of cognition and knowledge and, conversely, how constructivist insights (such as that the process of cognition is the process of life) (...) can inspire new models of computing. Method: The info-computational constructive framework is presented for the modeling of cognitive processes in cognizing agents. Parallels are drawn with other constructivist approaches to cognition and knowledge generation. We describe how cognition as a process of life itself functions based on info-computation and how the process of knowledge generation proceeds through interactions with the environment and among agents. Results: Cognition and knowledge generation in a cognizing agent is understood as interaction with the world (potential information), which by processes of natural computation becomes actual information. That actual information after integration becomes knowledge for the agent. Heinz von Foerster is identified as a precursor of natural computing, in particular bio computing. Implications: IC provides a framework for unified study of cognition in living organisms (from the simplest ones, such as bacteria, to the most complex ones) as well as in artifactual cognitive systems. Constructivist content: It supports the constructivist view that knowledge is actively constructed by cognizing agents and shared in a process of social cognition. IC argues that this process can be modeled as info-computation. (shrink)

Philosophy and Phenomenological Research, EarlyView.

There has been a recent explosion of interest in the epistemology of disagreement. Much of the recent literature is concerned with a particular range of puzzle cases (discussed in the Cases section of my paper). Almost all of the papers that contribute to that recent literature make mention of questions about religious disagreement in ways that suggest that there are interesting connections between those puzzle cases and real life cases of religious disagreement. One important aim of my paper is to (...) cast doubt on that suggestion. More generally, the aim of my paper is to give a reasonably full account of the recent literature on the epistemology of disagreement, and then to give a serious discussion of some of the epistemological issues that are raised by real world religious disagreements. (shrink)

Feser (2017) presents and defends five proofs of the existence of God. Each proof is in two stages: the first stage proves the existence of something which, in the second stage, is shown to possess an appropriate range of divine attributes. Each proof is given two presentations, one informal and one formal. In this paper, I critically examine two premises from one of Feser's five first stage proofs. I provide reasons for thinking that naturalists reject both of these premises. In (...) my view, this enough to show that the proof fails: it fails to advance considerations that decide between theism and important competing positions. (shrink)

This paper provides a taxonomy of cosmological arguments and givesgeneral reasons for thinking that arguments that belong to a given category do not succeed.

This paper is a reply to Professor William Lane Craig's “Graham Oppy On The kalām Cosmological Argument” Sophia 32.1, 1993, pp. 1–11. Further references to the literature are contained therein.

It is uncontroversial that artifacts like statues and tables are mind-dependent. What is controversial is whether and how this mind-dependence has implications for the ontology of artifacts. I argue the mind-dependence of artifacts entails that there are no artifacts or artifact joints in the extra-mental world. In support of this claim, I argue that artifacts and artifact joints lack any extra-mental grounding, and so ought not to have a spot in a realist ontology. I conclude that the most plausible story (...) about artifacts is that they are in minds of suitably intelligent creatures, and not the extra-mental world. Artifacts and their joints are merely mental projections onto a world of ‘indifferent materials’. With this established, I show how many cases of object coincidence, the view that more than one material object can be located in the same exact region of space-time, cannot occur. (shrink)

Robert Audi’s Seeing, Knowing, and Doing argues that knowledge does not entail justification, given a broadly externalist conception of knowledge and an access internalist conception of justification, where justification requires the ability to cite one’s grounds or reasons. On this view, animals and small children can have knowledge while lacking justification. About cases like these and others, Audi concludes that knowledge does not entail justification. But the access internalist sense of “justification” is but one of at least two ordinary senses (...) of the term. On a broader or looser sense, “justification” means “being in the right” where that involves meeting a standard or norm. I argue that the beliefs of animals and small children can then meet standards or norms associated with truth and knowledge such that their beliefs may count as justified in this broader or looser sense. I then question whether knowledge fails to entail justification on this broader sense. (shrink)

Moral dilemmas can arise from uncertainty, including uncertainty of the real values involved. One interesting example of this is that of experimentation on human embryos and foetuses, If these have a moral stauts similar to that of human persons then there will be server constraitns on what may be done to them. If embryous have a moral status similar to that of other small clusters of cells, then constraints will be motivated largely by consideration for the persons into whom the (...) embryos may develop. If the truth lies somewhere between these two extremes, the embryo having neither the full moral weight of persons, nor a completely negligible moral weight, then different kinds of constraints will be appropriate. On the face of it, in order to know what kinds of experiements, if any, we are morally justified in performing on embryos we have to know what the moral weight of the embryo is. But then an impasse threatens, for it seems implausible that we can settle with certainty the exact moral status of the human embryo. It is the purpose of this paper to show that moral uncertainty need not make rational moral justification impossible. I develop a framework which distinguishes between what is morally right/wrong, and what is morally justified/unjustified, and applies standard decision theoretic tools to the case of moral uncertainties. (This was the first published account of what has subsequently become known as Expected Moral Value Theory. An earlier version of the paper, "A decision theoretic argument against human embryo experimentation", was published in M. Fricke (ed.), Essays in honor of Bob Durrant. (University of Otago Press, 1986) 111-27.). (shrink)

This paper is a critical examination of some of the major themes of Brian Leftow's book *God and Necessity*.

Anselmian theists claim (a) that there is a being than which none greater can be conceived; and (b) that it is knowable on purely—solely, entirely—a priori grounds that there is a being than which none greater can be conceived. In this paper, I argue that Anselmian Theism gains traction by conflating different interpretations of the key description ‘being than which no greater can be conceived’. In particular, I insist that it is very important to distinguish between ideal excellence and maximal (...) possible excellence. At the end of my paper, I illustrate the importance of this distinction by applying my discussion to the recent defence of Anselmian Theism in Nagasawa (Philos Q 58:577–591, 2008). (shrink)

In this paper, I will argue that Locke is a substance dualist in the general sense, in that he holds that there are, independent of our classificatory schema, two distinct kinds of substances: wholly material ones and wholly immaterial ones. On Locke’s view, the difference between the two lies in whether they are solid or not, thereby differentiating him from Descartes. My way of establishing Locke as a general substance dualist is to be as minimally committal as possible at the (...) outset, especially with respect to the classic debates on Locke’s positions in this domain, including those concerning substrata, real essences, and the like. Nonetheless, I show that minimal commitments about Locke’s primary/secondary quality distinction are sufficient to derive some substantive conclusions about his positions on these issues, as well as that he is a general substance dualist. (shrink)

Hylomorphism is the Aristotelian theory according to which substances are composites of matter and form. If my house is a substance, then its matter would be a collection of bricks and timbers and its form something like a structure that unites those bricks and timbers into a single substance. Contemporary hylomorphists are divided on how to understand forms best, but a prominent group of theorists argue that forms are emergent powers. According to such views, when material components are arranged appropriately, (...) a novel substance emerges with the power to impose unity on its components through time. I argue that these accounts of form fall prey to a bootstrapping problem, and so, suffer from issues of redundancy, given plausible assumptions about inherence. In their place, I suggest an ontologically minimalist conception of forms as collective manifestations of the powers of matter. (shrink)

Among challenges to Molinism, the challenge posed by divine prophecy of human free action has received insufficient attention. We argue that this challenge is a significant addition to the array of challenges that confront Molinism.

The norm of assertion, to be in force, is a social norm. What is the content of our social norm of assertion? Various linguistic arguments purport to show that to assert is to represent oneself as knowing. But to represent oneself as knowing does not entail that assertion is governed by a knowledge norm. At best these linguistic arguments provide indirect support for a knowledge norm. Furthermore, there are alternative, non-normative explanations for the linguistic data (as in recent work from (...) Van Elswyk). Direct arguments would rely on normative judgments about the permissibility or impermissibility of assertions with and without the speaker knowing the content asserted. John Turri's work experimental results purport to show that our norm of assertion is factive, and probably knowledge. But as a number of recent experimentalists (Kneer, Reuter and Broessel, Marsili and Wiegmann) have shown, Turri's results rely on the problemmatic use of 'should' as in 'Maria should assert that she owns a 1990 watch.' Correcting for this, these experimentalists provide strong evidence that our norm of assertion is not factive. The standard reply to evidence like this from the assertion of unlucky falsehoods is the excuse maneuver. But Marsili and Wiegmann, following Turri's protocol for testing for excuse validation, show that participants who judge that assertions unlucky falsehoods are permissible are not guilty of excuse validation. Given our current understanding of the experimental evidence, knowledge is not our norm of assertion. (shrink)

I provide a classification of varieties of pantheism. I argue that there are two different kinds of commitments that pantheists have. On the one hand, there is an ontological commitment to the existence of a sum of all things. On the other hand, there is an ideological commitment: either collectively or distributively, the sum of all things is divine.

In On the Nature and Existence of God, Richard Gale follows majority opinion in giving very short shrift to the doctrine of divine simplicity: in his view, there is no coherent expressible doctrine of divine simplicity. Rising to the implicit challenge, I argue that---contrary to what is widely believed---there is a coherently expressible doctrine of divine simplicity, though it is rather different from the views that are typically expressed by defenders of this doctrine. At the very least, I think that (...) I manage to show that there are ways of understanding the doctrine of divine simplicity that have not yet been adequately examined. (shrink)

I argue that the Hume of the Treatise maintains an account of knowledge according to which (i) every instance of knowledge must be an immediately present perception (i.e., an impression or an idea); (ii) an object of this perception must be a token of a knowable relation; (iii) this token knowable relation must have parts of the instance of knowledge as relata (i.e., the same perception that has it as an object); and any perception that satisfies (i)-(iii) is an instance (...) of knowledge. I then apply this account to the case of sense perception. I argue that Hume holds that relations of impressions can be intuited, are knowable, and are necessary. For Hume, these relations constitute sensory knowledge. While Hume is rightly labeled an empiricist for many reasons, a close inspection of his account of knowledge reveals yet another way in which he deserves the label. (shrink)

In “On Oppy’s Objections to the Modal Perfection Argument,” Philo 8, 2, 2005, 123–30, Robert Maydole argues that his modal perfection argument—set out in his “The Modal Perfection Argument for a Supreme Being,” Philo 6, 2, 2003, 299–313—“remains arguably sound” in the face of the criticisms that I made of this argument in my “Maydole’s 2QS5 Argument,” Philo 7, 2, 2004, 203–11. I reply that Maydole is wrong: his argument is fatally flawed, and his attempts to avoid the criticisms that (...) I have made of his argument are to no avail. (shrink)

This paper discusses a range of modal ontological arguments. It is claimed that these modal ontological arguments fail because they depend upon controversial assumptions about the nature of modal space.

Some of Aristotle’s statements about the indemonstrability of the Principle of Non-Contradiction (PNC) in Metaphysics Γ 4 merit more attention. The consensus seems to be that Aristotle provides two arguments against the demonstrability of the PNC, with one located in Γ 3 and the other found in the first paragraph of Γ 4. In this article, I argue that Aristotle also relies upon a third argument for the same conclusion: the argument from truth. Although Aristotle does not explicitly state this (...) argument, it is the best argument that he could use to defend some of his statements in the second paragraph of Γ 4. Since the argument relies on only a few of Aristotle’s core views about truth, I propose that it is faithful to his considered position throughout his corpus, and it may be the strongest argument he could offer for the indemonstrability of the PNC. (shrink)

In his Critique of Pure Reason Immanuel Kant presents four antinomies. In his attempt to solve the first of these antinomies he examines and analyzes "thesis" and "antithesis" more thoroughly and employs the terms `part', `whole' and `boundary' in his argumentation for their validity. According to Kant, the whole problem surrounding the antinomy was caused by applying the concept of the world to nature and then using both terms interchangeably. While interesting, this solution is still not that much more than (...) a well thought out idea if it does not also include an adequate formal explication. Since the aforementioned terms all have counterparts in modern mereotopology, a discipline that has seen significant progress in recent times, we will apply these concepts to Kant's analysis in an attempt to evaluate Kant's solution in light of modern analytic philosophy. (shrink)

We compare the medieval projects of commentaries and disputations with the modern projects of formal ontology and of mathematics.

Craig (1981) presents and defends several different kalam cosmological arguments. The core of each of these arguments is the following ur argument.

There are some necessary conditions on causal relations that seem to be so trivial that they do not merit further inquiry. Many philosophers assume that the requirement that there could be no temporal gaps between causes and their effects is such a condition. Bertrand Russell disagrees. In this paper, an in-depth discussion of Russell’s argument against this necessary condition is the centerpiece of an analysis of what is at stake when one accepts or denies that there can be temporal gaps (...) between causes and effects. It is argued that whether one accepts or denies this condition, one is implicated in taking on substantial and wide-ranging philosophical positions. Therefore, it is not a trivial necessary condition of causal relations and it merits further inquiry. (shrink)

Hylomorphism is the Aristotelian theory according to which substances are composed of matter and form. If a house is a substance, then its matter would be a collection of bricks and timbers and its form something like the structure of those bricks and timbers. It is widely agreed that matter bears a mereological relationship to substance; the bricks and timbers are parts of the house. But with form things are more controversial. Is the structure of the bricks and timbers best (...) conceived as a part of the house, or is it related to the house in some non-mereological fashion? Kathrin Koslicki argues that substances have formal parts, that forms are best conceived as bearing a mereological relation to substances. This paper shows that her argument fails, given the traditional and plausible distinction between substances and accidental unities. I close with a brief suggestion for a non-mereological construal of forms. (shrink)

This introductory article outlines how this special issue contributes to existing scholarship that calls for a rethinking and re-evaluation of common assumptions about early modern philosophy. One way of challenging existing narratives is by questioning what role systems or systematicity play during this period. Another way of rethinking early modern philosophy is by considering assumptions about the role of philosophy itself and how philosophy can effect change in those who form philosophical beliefs or engage in philosophical argumentation. A further way (...) of advancing early modern scholarship is by examining the tight links between early modern views on metaphysics and epistemology, on the one hand, and moral, social, and political philosophy, on the other hand. Moreover, there are ongoing debates whether and how the traditional distinction between rationalism and empiricism, which has been questioned for several reasons, should be replaced. It has been proposed to replace it with a distinction between experimental and speculative philosophy, but this distinction cannot easily accommodate early modern debates concerning moral, social, and political philosophy. In addition to highlighting several ways how early modern philosophy has and can be rethought, we summarize how the papers in this special issue contribute to these ongoing efforts. (shrink)