Considerable recent research in neurosciences has dealt with the topic of consciousness, even though there is still disagreement about how to identify and classify conscious states. Recent behavioral work on the topic also exists. We survey recent behavioral and neuroscientific literature with the aims of commenting on strengths and weaknesses of the literature and mapping new directions and recommendations for experimental psychologists. We reconcile this literature with a view of human information processing (Cowan, 1988; Cowan et al., 2024) in which (...) a capacity-limited focus of attention is embedded within the activated portion of long-term memory, with dual bottom-up and top-down control of the focus of attention. None of the many extant theories fully captures what we propose as the organization of conscious thought at cognitive and neural levels. It seems clear that information from various cognitive functions, based on signals from various brain areas, is integrated into a conscious whole. In our new proposal, the integration involves funneling information to a hub or focus of attention neurally centered in the parietal lobes and functionally connected to areas representing the currently attended information. This funneling process (bringing information from diverse sensory and frontal sources to contact a small parietal area where attended information is coordinated and combined) may be the converse of global broadcasting, from other proposals (Baars et al., 2021; Baars & Franklin, 2003; Dehaene & Changeux, 2011). The proposed system incorporates many principles from previous research and theorization and strives toward a resolution of the relation between consciousness and attention. Keywords: consciousness, attention, embedded processes model, experimental psychology, neuroscience. (shrink)

D. C. Matthew argues that although integration offers blacks social and economic benefits, it also creates the conditions for phenotypic devaluation that leads to harm against black self-worth and servile behavior. Therefore, he advises against integration because the resulting self-worth harms outweigh the benefits of integration. I argue that Matthew’s cost-benefit calculation against integration lacks the requisite evidence, and amounts to a luxury belief that will result in more harm. Moreover, his interpretation of behavior — which he construes as being (...) indicative of a lack of self-worth — is unfounded. Further, his cost-benefit calculation results in socially reactionary sexual policing and ideological purity tests. (shrink)

This book is a case of “too little, too late”: too little in that it represents voices not from the developing world as a whole but from a particular Catholic viewpoint in the Philippines, too late in that others have already gone “beyond a Western bioethics”—which, in any case, is not the unified and rigid set of principles that the authors make it out to be. The publication is a long delayed spinoff of a series of bioethics seminars held in (...) Manila and Houston under the leadership of H Tristram Engelhardt Jr, who has contributed an introduction to the volume on Western bioethics reconsidered. (As Engelhardt writes: “Like good wine, this work has come slowly into its own” (page xii). Engelhardt’s bias is evident in the phrase he uses early on in this introduction, “the customary American/western European indoctrination in …. (shrink)

The realist belief in robustly attitude-independent evaluative truths – more specifically, moral truths – is challenged by Sharon Street’s essay “A Darwinian Dilemma for Realist Theories of Value”. We know the content of human normative beliefs and attitudes has been profoundly influenced by a Darwinian natural selection process that favors adaptivity. But if simple adaptivity can explain the content of our evaluative beliefs, any connection they might have with abstract moral truth would seem to be purely coincidental. She continues the (...) skeptical attack in “Objectivity and Truth: You’d Better Rethink It”, concentrating on the intuitionist realism of Ronald Dworkin. The latter sees the issue fundamentally as a holistic choice between moral objectivity and the genocide-countenancing consequences of abandoning objective standards. Street counters that, because of realism’s skeptical difficulties, Dworkin’s Choice (as I call it) actually works in favor of her Euthyphronic antirealism. I will argue that she misrepresents the realist’s skeptical challenge, and that clarifying the character of that challenge renders the case for normative realism much more appealing. Indeed, I claim that Street fails to exclude the genuine possibility of a rational basis for moral truth. (shrink)

Distributed cognition (d-cog) claims that many cognitive processes are distributed across groups and the surrounding material and cultural environment. Recently, Nancy Nersessian, Ronald Giere, and others have suggested that a d-cog approach might allow us to bring together cognitive and social theories of science. I explore this idea by focusing on the specific interpretation of d-cog found in Edwin Hutchins' canonical text Cognition in the wild. First, I examine the scope of a d-cog approach to science, showing that there (...) are important disputes between cognitive and social theorists on which d-cog remains silent. Second, I suggest that, where social explanations can be recast in d-cog terms, this reformulation will not be acceptable to all social theorists. Finally, I ask how we should make sense of the claim that, on a d-cog analysis, social factors are cognitive factors. (shrink)

Regarding the relation of Plato’s early and middle period dialogues, scholars have been divided to two opposing groups: unitarists and developmentalists. While developmentalists try to prove that there are some noticeable and even fundamental differences between Plato’s early and middle period dialogues, the unitarists assert that there is no essential difference in there. The main goal of this article is to suggest that some of Plato’s ontological as well as epistemological principles change, both radically and fundamentally, between the early and (...) middle period dialogues. Though this is a kind of strengthening the developmentalistic approach corresponding the relation of the early and middle period dialogues, based on the fact that what is to be proved here is a essential development in Plato’ ontology and his epistemology, by expanding the grounds of development to the ontological and epistemological principles, it hints to a more profound development. The fact that the bipolar and split knowledge and being of the early period dialogues give way to the tripartite and bound knowledge and benig of the middle period dialogues indicates the development of the notions of being and knowledge in Plato’s philosophy before the dialogues of the middle period. -/- Keywords Plato; early dialogues; middle dialogues; being; knowledge; development -/- Introduction The differences between two groups of the early and middle period dialogues have always been a matter of dispute. Whereas the developmentalists like Vlastos, Silverman (2002), Teloh (1981), Dancy (2004) and Rickless (2007) think that from the early to the middle dialogues Plato’s philosophy changes, at least in some essential points, the unitarists like Kahn, Cherniss and Shorey believe that there happens no development and the differences must be taken as natural, ignorable and even pedagogic. In his well-known article, Socrates contra Socrates in PLATO, Vlastos lists ten theses of difference between two groups of dialogues. The first group which includes Plato’s early dialogues he divides to 'elenctic' (Apology, Charmides, Crito, Euthyphro, Gorgias, Hippias Minor, Ion, Laches, Protagoras and Republic I) and 'transitional' (Euthydemus, Hippias Major, Lysis, Menexenus and Meno) dialogues. These transitional come after all the elenctic dialogues and before all the dialogues of the second group which compose Plato’s middle period dialogues, including (with Vlastos' chronological order) Cratylus, Phaedo, Symposium, Republic II-X, Phaedrus, Parmenides and Theaetetus (1991, 46-49). Vlastos asserts strictly that his list of differences are 'so diverse in content and method that they contrast as sharply with one another as with any third philosophy you care to mention, beginning with Aristotole’s' (ibid, 46). Vlastos’ list of differences between two Socrateses is considered a view breaking sharply between the early and the middle dialogues. Besides all ten differences between the two Socrateses in Vlastos’ list that can be supportive for our doctrine here, we intend to focus on some ontological as well as epistemological distinctions that have not completely been discussed hitherto. Contrary to the developmentalist theory of Vlastos, unitarian theory of Charles Kahn wishes to eliminate any substantial difference between the early and the middle dialogues. He distinguishes seven 'pre-middle' or 'threshold' dialogues including Laches, Charmides, Euthyphro, Protagoras, Meno, Lysis and Euthydemus from the other Socratic dialogues which he calls 'earliest group' (1996, 41). The threshold dialogues, Kahn thinks, 'embarke upon a sustained project' that is to reach to its climax in the middle period dialogues, namely Phaedo, Symposium and Republic. Believing in that there is no 'fundamental shift'between the early and middle dialogues (ibid, 40), Kahn thinks the Socratic dialogues are just the 'first stage' with a 'deliberate silence' towards the theories of later periods (ibid, 339). One of the reasons of the surprising fact that Plato gives no hint of the metaphysics and epistemology of the Forms in the early dialogues, he thinks, is the pedagogical advantages of aporia. He thinks that Plato 'obscurely', and mostly because of education, hinted to some doctrines and conceptions in his early dialogues and with the aim of clarifying them only in the later ones (ibid, 66). The seven threshold dialogues, Kahn asserts, 'had been designed from the first' to prepare the pupils and readers for the views expounded in the middle period dialogues (ibid, 59-60). To show that the differences of the two Socrateses of the early and middle period dialogue are in their onto-epistemological grounds and thence cannot be explained by a unitaristic view, we try to draw the ontological and epistemological principles of the early dialogues in the first part below in order to show, in the second part, that those principles have been developed in the middle period dialogues. -/- A. The Onto-Epistemologic Principles of the Early Dialogues Socratic dialogues are paradoxical about knowledge because while being knowledge-oriented always searching for knowledge, they deny it and even never discuss it directly. Three elements of Socrates’ way of searching Knowledge throughout the early dialogues, i.e. Socratic 'what is X?' question, his disavowal of knowledge and his elenctic method combined together produce something like a circle which works, more or less, in the same way in these dialogues. Though this circle is an embaressing inquiry always resulting in ignorance instead of knowledge, its motivation is surprisingly Socrates’ passionate enthusiasm for knowledge, an intensive love of wisdom. The starting point of this circle is Socrates’ confession of having no knowledge which might be explicitly asserted or presupposed, maybe because it was one of the famous characteristics of Socrates; a confession always paradoxically accompanied with his intense longing for knowledge (e.g., Gorgias 505e4-5). Every time Socrates encounters with someone who thinks he knows something (οἴεταί τι εἰδέναι) (Apology 21d5) and tries to examine him. This examination seems to be the simplest one asking just what it is that he knows. Socrates’ elenchus, therefore, is always connected with 'what is X?' (τίς ποτέ ἐστιν) question, a question that most of the early dialogues of Plato are concerned with; 'what is courage?' in the Laches, 'what is piety?' in Euthydemus, 'what is temperance?' in Charmides and 'what is beauty?' in Hippias Major. This question we call here 'Socratic question' and probably is the very question the historical Socrates used to employ, is tightly interrelated with both his disavowal and his elenchus. He disclaims knowledge because he cannot find the answer to the question himself and he rejects others’ since they cannot offer the correct answer too. Every interlocutor can claim he knows X, if and only if he can answer the Socratic question. Otherwise, he is more of an ignorant than of a knower of τί ποτέ ἐστι X. Knowing the answer to this question is, thus, knowledge’s criterion for Socrates. Having found out that he cannot answer what it is which he would claim to know, the interlocutor comes to the point Socrates was there at the beginning. The least advantage of this circle is that he becomes as wise as Socrates does about the subject, becoming aware that he does not know it. At the end of the circle they are both still at the beginning, not knowing what X is. So let us first take a glance at these three elements. Socratic disavowal of knowledge is strictly asserted in some passages. At Apology 21b4-5, Socrates says: -/- I do not know of myself being wise at all (οὔτε μέγα οὔτε σμικρὸν σύνοιδα ἐμαυτῷ σοφὸς ὤν) -/- Moreover, at 21d4-6: -/- None of us knows anything worthwhile (καλὸν κἀγαθὸν εἰδέναι) …. I do not know (οἶδα) neither do I think I know. -/- In Charmides Socrates speaks about a fear about his probable mistake of thinking that he knows (εἰδέναι) something when he does not (166d1-2). The somehow generalization of this disavowal can be seen in Gorgias. After calling his disavowal 'an account that is always the same' (509a4-5), Socrates continues (a5-7): -/- I say that I do not know (οἶδα) how these things are, but no one I have ever met, like now, who can say anything else without being absurd. -/- At the end of Hippias Major (304d7-8), Socrates affirms his disavowal of knowledge of 'what is X?' this time about the fine: -/- I do not know (οἶδα) what that is itself (αὐτὸ τοῦτο ὅτι ποτέ ἐστιν). Some other passages, however, made a number of scholars dubious about Socrates’ disavowal. Vlastos mentions Apology 29b6-7 as an evidence : 'that to do wrong and to disobey one’s master, both god and men, I know (οἶδα) to be evil and shameful'. He thinks that if we give this single text 'its full weight' it can suffice to show that Socrates does claim knowledge of a moral truth (1985, 7). Vlastos’ claim is not admittable since it would be too strange, I think, for a man like Socrates to violate his disavowal claim just after emphasizing it. We can see his claim just before the already mentioned passage: -/- And surely it is the most blameworthy ignorance to believe that one knows what one does not know. It is perhaps on this point and in this respect, gentlemen, that I differ from the majority of men and if I were to claim that I am wiser than anyone in anything it world be in this, that, as I have no adequate knowledge (οὐκ εἰδὼς ἱκανῶς) of things in the underworld, so I do not think I have (οὐκ εἰδέναι) (Apology 29b1-6) Vlastos tries to solve what he calls the 'paradox' of Socrates’ disavowal of knowledge distinguishing the 'certain' knowledge from 'elenctic' knowledge (1985, 11) and thinking that when Socrates avows knowledge, we must perceive it as an elenctic knowledge, a knowledge its content 'must be propositions he thinks elenctically justifiable' (ibid, 18). Irwin’s solution is the distinction of knowledge and belief. He approves that Socrates does not 'explicitly' make such a distinction, but still thinks that Socrates’ 'test for knowledge would make it reasonable for him to recognize true belief without knowledge, and his own claims are easily understood if they are claims to true belief alone' (1977, 40). While I agree with Vlastos up to a point, I strongly disagree with Irwin about the early dialogues. As I will try to show below, we are not permitted to consider any kind of distinction within knowledge in Socratic dialogues because only one category of knowledge is alluded to there and the distinction of knowledge and belief thoroughly belongs to the second Sorcates. Although no kind of distinction can be admittable here, I think Vlastos’ distinction can be accepted only if we regard it as a distinction between knowledge, which is unique and without any, even incomparable, rival, and a semi-idiomatic and ordinary one that is a necessary requirement for any argument, and thus, unavoidable even for someone who does not claim any kind of knowledge. An apparent evidence of this is Gorgias 505e6-506a4: -/- I go through the discussion as I think it is (ὡς ἄν μοι δοκῇ ἔχειν), if any of you do not agree with admissions I am making to myself, you must object and refute me. For I do not say what I say as I know (οὐδὲ γάρ τοι ἔγωγε εἰδὼς λέγω ἃ λέγω) but as searching jointly with you (ζητῶ κοινῇ μεθ᾽ ὑμῶν). -/- The minimal degree of knowledge everyone must have to take part in an argument, conduct it and use the phrase "I know" when it is necessary is what Socrates cannot deny. We can call it elenctic knowledge only if we agree that it is not the kind of knowledge that Socrates has always been searching, the one that can be accepted as the answer of Socratic 'what is X?' question. His disavowal of knowledge is applied only to the knowledge which can truly be the answer of Socratic question and pass the elenctic exam; a knowledge that, I believe, is never claimed by first Socrates. Socrates conducts his method of examining his interlocutors’ knowledge, our second element here, by almost the same method repeated in Socratic dialogues. That whether we are allowed to regard all the examinations of Socrates in the early dialogues as based on the same or not has been a matter of dispute. Vlastos himself (1994, 31) distinguished Euthydemas, Lysis, Menexenns and Hippias Major from the other Socratic dialogues because he thinks Socrates has lost his faith to elenchus in there. Irwin (1977, 38) distinguishes Apology and Crito where Socrates’ own convictions is present. Contrary to some scholars like Benson (2002, 107) who take elenchus in all the Socratic dialogues as a unique method, Michelle Carpenter and Ronald M. Polansky (2002, 89-100) argue pro the variety of methods of elenchus. Thomas C. Brickhouse and Nicholas D. Smith (2002, 145-160) even reject such a thing as Socratic elenchus which can gather all of the Socrates’ various arguments under such a heading. There can be no solution for the problem of elenchus, they think, is due to 'the simple reason that there is no such thing as 'the Socratic elenchos"'(p.147). Though we consider elenchus a somehow determined process and a part of Socratic circle in the early dialogues, all we assume is that whatever differences it might have in different dialogues, it has the same onto-epistemological principles and, thus, we are not going to take it necessarily as a unique method. This method sets out to prove that the interlocutors are as ignorant as Socrates himself is. That whether elenchus is constructive, capable of establishing doctrines as Vlastos (1994) or Brickhouse and Smith (1994, 20-21) believe or not is another issue to which this paper is not to claim anything. What is crucial for our discussion here is that elenchus does not reach to the very knowledge Socrates is looking for. This is strictly against Irwin who thinks that not only elenchus leads to positive results, 'it should even yield knowledge to match Socrates’ conditions'(1977, 68, cf. 48). He does not explain where and how they really yield to that kind of knowledge. He explains his elenctic method in his apology in the court (Apology 21-22), that how he used to examine wise men, politicians, poets and all those who had the highest reputation for their knowledge and every time found that they have no knowledge. If we accept, as I strongly do, that Socrates’ disavowal of his knowledge is not irony, it might seem more reasonable to agree that the process that has that disavowal as its first step cannot be irony as well. The key of the circle which can explain why Socrates disclaims knowledge and how he can reject others’ claim of having any kind of knowledge lies in the third element, Socratic question. In Hippias Major (287c1-2), Socrates asks: 'Is it not by Justice that just people are Just? (ἆρ᾽ οὐ δικαιοσύνῃ δίκαιοί εἰσιν οἱ δίκαιοι). He insists at 294b1 that they were searching for that by which (ᾧ) all beautiful things are beautiful (cf. b4-5, 8). At Euthyphro 6d10-11 it is said that the Socratic question is waiting for 'the form itself (αὐτὸ τὸ εἶδος) by which (ᾧ) all the pious actions are pious; and at 6d11-e1: -/- Through one form (που μιᾷ ἰδέᾳ) impious actions are impious and pious actions pious. -/- Since the X itself is that by which X is X, knowing 'X itself' is the only way of knowing X. It is probably because of this that Socrates makes the distinction between the ousia as a right answer to the question and effect as a wrong one: -/- I am afraid, Euthyphro, that when you were asked what piety is (τὸ ὅσιον ὅτι ποτ᾽ ἐστίν) you did not wish to make clear its nature itself (οὐσίαν … αὐτοῦ) to me, but you said some effect (πάθος) about it. (Euthp. 11a6-9) -/- 1. Knowledge of what X is Now it is time to look for the onto-epistemological principles of Socratic circle and its three elements. It cannot reasonably be expected from the first Socrates to present us explicitly and clearly formulated principles of his onto-epistemology when such explications cannot be found even in the second Socrates who has some obviously positive theoris. Since there must be some principles underlying this first systematic inqury of knowledge, we must seek to them and be satisfied with elicitation of the first Socratas’ principle. What will be drawn out as his principles cannot and must not, thus, be taken as very fix and dogmatic principles. Some very slightest principles and grounds suffice for our purposes here. The first principle that is the prima facie significance of the Socratic question and his implementation of all those elenctic arguments I call the principle of 'Knowledge of What X is' (KWX): -/- KWX To know X, it is required to know what X is. -/- Aristotle (Metaphysics 1078b23-25, 27-29, 987b4-8) takes Plato’s τί ἐστι question as seeking the definition of a thing that is the same as historical Socrates’ search but applying to a different field. That Plato’s 'what is X?' question was a search for definition became the prevailed understanding of this question up to now. I am going neither to discuss the answer of Socratic question nor to challenge taking it as definition. What I am to insist is that knowledge is attached firmly to the answer of the question: Knowledge of X is not anything but the knowledge of what X is. It entails, certainly, the priority of this knowledge to any other kind of knowledge about X but it also has something more fundamental about the relation of knowledge and Socratic question. Socrates’ exclusive focus on the answer of his question can authorize the consideration of such an essential role for KWX in his epistemolgoy. The total rejection of his interlocutors’ knowledge when they are unable to answer the question can be regarded as a strong evidence for it. Socrates’ elenctic method and his rejection of others’ knowledge in the early dialogues, which all end aporetically with no one accepted as knower and nothing as knowledge, prevent us from finding any positive evidence for this. We have to be content, therefore, of negative evidences which, I think, can be found wherever Socrates rejects his interlocutors’ knowledge when they are not able to give an acceptable answer to his 'what is X?' question. 2. Bipolar Epistemology Socrates’ rejection of his interlocutors’ knowledge has another epistemological principle as its basis. Let me call this principle Bipolar Epistemology' (BE): BE There is no third way besides knowledge and Ignorance. -/- BE says that about every object of knowledge there are only two subjective statuses: knowledge and Ignorance. Socrates’ disavowal, however, says nothing but that he is ignorant of knowledge of X because he does not know what X is. This means that BE is presupposed here. Socrates’ elenchus and his rejection of interlocutors’ having any kind of knowledge are the necessary results of the fact that he does not let any third way besides knowledge and ignorance. The first Socrates never let anyone partly know X or have a true opinion about it, as he would not let anyone know anything about X when he did not know what X is. -/- 3. Bipolar Ontology The principle of BE in first Socrates’ epistemology is parallel to another principle in his ontology. Plato’s bipolar distinction between being and not being is as strict and perfect as his distinction between knowledge and ignorance. This principle I shall call the principle of 'Bipolar Ontology' (BO): BO Being is and not being is not. BO is apparently the same with the well-known Parmenidean Principle of being and not being (cf. Diels-Kranz (DK) Fr. 2.2-5). Euthydemus’ statement against the possibility of false knowledge can be good evidence for this principle: -/- The things which are not surely do not exist (τὰ δὲ μὴ ὄντα … ἄλλο τι ἢ οὐκ ἔστιν). (Euthydemus 284b3-4) -/- He continues (b4-5): -/- There is nowhere for not being to be there (οὖν οὐδαμοῦ τά γε μὴ ὄντα ὄντα ἐστίν). -/- That BE does not let true opinion as a third option besides knowledge and ignorance seems to be related to BO’s rejecting a third option besides being and not being, which is itself the basis of the impossibility of false belief. Socrates’ elaborate discussion of the problem of false belief in Theatetus that leads to a more decisive discussion and finally to some solutions in Sophist can make our consideration of BO for the first group of dialogues authentive. -/- 4. &5. Split Knowledge and Split Being The fourth principle I shall call the principle of 'Split Knowledge' (SK): -/- SK Knowledge of X is separated from any other knowledge (of anything else) as if the whole knowledge is split to various parts. -/- This Principle is hinted and criticized as Socrates’ way of treating with knowledge in Hippias Major: -/- But Socrates, you do not contemplate the entireties of things, nor do people you have used to talk with (τὰ μὲν ὅλα τῶν πραγμάτων οὐ σκοπεῖς, οὐδ᾽ ἐκεῖνοι οἷς σὺ εἴωθας διαλέγεσθαι). (301b2-4) -/- Contrary to Rankin who regards the passage as 'antilogical, almost eristic in tone rather than presenting a serious philosophy of being' (1983, 54), I think it can be taken as serious. Hippias criticizes Sorcates that he does not contemplate (σκοπεῖς) the entireties of things (ὅλα τῶν πραγμάτων), a critique which Socrates is not its only subject but all those whom Socrates accustomed to talk with (ἐκεῖνοι οἷς σὺ εἴωθας διαλέγεσθαι). This last phrase, I think, extends this critic beyond this dialogue to other Socratic dialogues. Hippias’ use of the perfect tense of the verb ἔθω (to be accustomed) is a good evidence of this extension. We can get, thus, these ἐκεῖνοι as Socrates’ interlocutors in his other dialogues that hints that this criticism has the epistemological groundings of the previous dialogues as its subject. What ἐκεῖνοι οἷς σὺ εἴωθας διαλέγεσθαι points to is that Hippias does not have in mind Socrates’ way of treating things only in this dialogue, but he is also criticizing Socrates’ way throughout his dialogues. At 301b4-5, Socrates and his interlocutors’ way of beholding things is described as such: -/- You people knock (κρούετε) at the fine and each of the beings (ἕκαστον τῶν ὄντων) by taking each being cut up in pieces (κατατέμνοντες) in words (ἐν τοῖς λόγοις). This leads us to our next principle that is parallel to, and the ontological side of, SK, the principle of 'Split Being'(SB): -/- SB Everything (being) is separated from any other thing as if the whole being is split to many beings. -/- Socrates and his interlocutors and thus, as we saw, the Socratic dialogues are accused to regard everything as it is separated from all other things. This separation is en tois logois that, I think, can reasonably be taken as saying that Socratic dialogues (it refers of course to the dialogues before Hippias Major) cut up all things which have the same name/definition from all other things and try to understand them separately, without considering other things that are not in their logos. They, for example in Hippias Major, are cutting up to kalon and try to understand what it and all others inside this logos are by separating it from all other things. This is directed straightly against Socratic question and the way Socratic dialogues follow to find its answer, every time separating one logos. As Meyer (1995, 85) points out, every question 'presupposes that the X in question in a logos is something' and 'every answer to every question aims at unity' (84). The critique of Hippias Major is, therefore, at the same time a critique of SK and SB. It is also a critique of KWX because it is only based on KWX that Socratic dialogues could search for the answer of 'what is X' question supposing that knowing what X is is enough for the knowledge of X. SK and KWX are absolutely interdependent. What Socrates and all his previous interlocutors have neglected in Socratic dialogues, Hippias says, was 'continuous bodies of being' (διανεκῆ σώματα τῆς οὐσίας) (301b6). Either this theory actually belongs to the historical Hippias as it is being said or not, it is strictly criticizing SB. We have the same phrase with changing sūma to logos some lines later at 301e3-4: διανεκεῖ λόγῳ τῆς οὐσίας. Although this theory that can be observed as both an ontological and an epistemological theory is rejected by Socrates (301cff.), it is still against first Socrates’ onto-epistemological principles and might let us look at what is rejected as Socratic prineple. -/- 6. Knowledge is of Being The sixth principle that I think is presupposed by the first Socrates, is the 'Knowledge of Being' Principle (KB): -/- KB Knowledge is of Being. -/- This principle is obviously the source of the problem of false knowledge, a very important problem throughout Plato’s philosophy. We face this problem maybe for the first time in Euthydemus. In less than 20 Stephanus’ pages, 276-295, we are encountered with different interwoven problems about knowledge , all grounded in the problem of false opinion. Having challenged the obvious possibility of telling lies at 283e, at 284 Euthydemus discusses it saying that the man who speaks is speaking about 'one of those things that are (ἓν μὴν κἀκεῖνό γ᾽ ἐστὶν τῶν ὄντων)' (284a3) and thus speaks what is (λέγων τὸ ὄν) (a5). He must necessarily be saying truth when he is speaking what is because he who speaks what is (τὸ ὄν) and the things that are (τὰ ὄντα) speaks truth (τἀληθῆ λέγει) (a5-6). This is based on Parmenidean principle of the impossibility of being of not being which Euthydemus restates (284b3-4) and we mentioned discussing BO principle above. The things that are not are nowhere (οὐδαμοῦ) and there is no possibility for anyone to do (πράξειεν) anything with them because they must be made as being before anything else can be done, which is impossible (b5-7). The words, then, are of things that exist (εἰσὶν ἑκάστῳ τῶν ὄντων λόγοι) (285e9) and as they are (ὡς ἔστιν) (e10). The result is that no one can speak of things as they are not. It is this impossibility of false speach that is extended to thinking (δοξάζειν) at 286d1 and leads to the impossibility of false opinion (ψευδής … δόξα) (286d4). The general conclusion is asserted at 287a extending this impossibility to actions and making any kind of mistake. Not only knowledge is of being but speech, thought and action are of being simply because of the fact that nothing can be of not being. -/- B. First Socrates’ Principles in the Middle Period Dialogues Out of what were presupposed or criticized mostly in five dialogues, Euthyphro, Euthydemus, Hippias Major, Laches and Charmides, we tried to draw the first Socrates’ principles. Our inquiry here is directed to find out the fate of these principles in the three dialogues of the middle period, Meno, Phaedo and Republic. To do this, first we ought to check the situation of Socratic circle in these dialogues. The Socratic circle that was predominant in the early dialogues, does not look like a circle here anymore though they certainly have some features in common. Meno, Phaedo and Republic II-X are not committed to the principles of the circle and the whole circle in disrupted in them. The difference of the two Socrateses towards acquiring knowledge is obvious. The Socrates of Meno, Phaedo and Republic is evidently more self-confident that he can get to some truths during his arguments as he does. They are in their first appearance, as almost all other dialogues, committed to Socrates’ disavowal. All of them try to keep the shape of the Socratikoi Logoi genre, which is committed to the historical Socrates’ way of discussion; a dramatic personage who is to challenge his interlocutors, ask them and refuse the answers. Nevertheless, the fact is that what we have in common between two groups of dialogues is mostly a dramatic structure. Whereas the first group’s arguments are based on Socrates’ disavowal and lead to no positive results, the second group is decisively going to achieve some positive results. The aim of the first Socrates was to show others that they are ignorant of what they thought they knew. The new Socrates of Meno, on the opposite, makes so much efforts to show that the slave boy has within himself true opinions (ἀληθεῖς δόξαι) about the things that he does not know (οἶδε) (85c6-7). Despite his lack of knowledge, he has true opinions nevertheless. The way from these true opinions to knowledge, as Socrates states, is not so long. These true opinions are now like a dream but 'can become knowledge of the same things not less accurate than anyone’s' (οὐδενὸς ἧττον ἀκριβῶς ἐπιστήσεται περὶ τούτων) (c11-d1), if they be repeated by asking the same questions. The most outstanding text regarding Socrates’ disavowal is Meno 98b where he explicitly claims knowledge: -/- And indeed I also speak as (ὡς) one who does not know (εἰδὼς) but is guessing (εἰκάζων). However, [about the fact] that true opinion and knowledge are different, I do not altogether expect (δοκῶ) myself to be guessing (εἰκάζειν), but if I say about anything that I know (εἰδέναι) -which about few things I say- this is one of the things that I know (οἶδα). (98b1-5) This passage is very significant about Plato’s disavowal of knowledge. There can hardly be found, I think, anywhere else in Plato’s corpus where Socrates speaks about his knowledge of something as such. He says first that he speaks as someone who does not know. This ὡς οὐκ εἰδὼς λέγω comparing with what he used to say in the first group, οὐκ οἶδα, has this added ὡς. Socrates does not claim strongly anymore that he does not know anything but speaks only as someone who does not know. He needs this ὡς not only because he is going to accept that he does know some, though few, things immediately after this sentence, but also because he needs his previous disavowal to be loosened from Meno on. He does not merely say here that he knows something. It is then different from the examples mentioned before which could be taken as idiomatic or at least not emphatic. Socrates’ remarkable emphasis on distinguishing εἰδέναι from εἰκάζειν departs it from all other passages where he says only he knows something. Moreover, he claims definitely that he has knowledge about few (ὀλίγα) things. From the early to the middle dialogues, Socrates’ attitude to knowledge has totally renewed its face. He brings forth a new concept, true opinion, and he does not speak of knowledge as he used to before; the rough, perfect and unachievable knowledge of the first group has turned to something more smooth, realistic and achievable. Comparing with the early dialogues that did not set out from the first to reach positive results, the middle ones are extraordinarily and surprisingly positive and hence destroy the basis of the Socratic circle. The questions and answers are purposely directed to some specific new theories; most of them are not directly related to the topics or the main questions of the dialogues. They are suggested when Socrates draws the attention of the interlocutor away from the main question because of the necessity of another discussion. Even if the main question remains unanswered, we have still many positive theories, prominently of metaphysical type. These theories are so abundant and dominant in these dialogues, especially Phaedo and Republic, that one might think that they may appear to be arbitrarily sandwiched in there. This helps dialogues to keep their original Socratic structure while they are suggesting new theories. Hence, the Socratic question of 'what is X?', though is still used to launch the discussion, is loosened and is forgotten for most part of the dialogues. Meno that has first a differently formulated question, 'can virtue be taught?', leads finally to the Socratic question of 'What is virtue?'. Phaedo is dedicated to the demonstration of the immortality of soul and the life after death without having a central Socratic question. The case of Republic is more complicated. The first book, on the one hand, has all the criteria of a Socratic circle: its 'what is justice?' question, Socrates’ strong disavowal (e.g. 337d-e), his rejection of all answers and coming back to the first point without finding out any answer. This Book, considered alone, is a perfect Socratic dialogue, as many scholars regard it as early and separated from other books. The books II-X are, on the other hand, far from implementing a Socratic circle. They have still the 'what is justice?' question as their incentive leading question, but they are, in most of the positive doctrines and methods that encompass the main parts, ignoring the question. Even these books that, I believe, are the farthest discussions from the Socratic circle are so cautious not to break the Socratic structure of the dialogue as long as it is possible. What is changed is not the structure of the dialogue but the ontological and epistemological grounds based on which new theories are suggested. -/- 1. Knowledge of the Good We can clearly see in the second group of dialogues that the KWX principle loses the place it had before in our first group. It is not, of course, rejected, but still we cannot say that it has the same situation. KWX that was based on Socratic question, as we discussed before, was the leading principle of the first Socrates’ epistemology and of the highest position. Other epistemological principles, SK directly and BE indirectly, were relying on Socratic question and therefore on KWX. Such a position does not belong to KWX from Meno on. What makes it different in the second Socrates is another principle that is needed it not only as its complementary principle but also as what is more fundamental. Plato, then, does not reject KWX in this period, but, it seems, he transcends to another more basic principle; a principle we shall call the principle of 'Knowledge of the Good' (KG): -/- KG Knowledge of X requires knowledge of the Good. -/- Whereas all the dialogues of our first group are free from any discuscon about KG, it bears a very important role in the second group so as becomes the superior principle of knowledge in Republic. Trying to solve the problem of teachability of virtue, Socrates says that it can be teachable only if it is a kind of knowledge because nothing can be taught to human beings but knowledge (ἐπιστήμην) (Meno 87c2). The dilemma will be, then, whether virtue is knowledge or not (c11-12) and since virtue is good, we can change the question to: whether is there anything good separate from knowledge (εἰ μέν τί ἐστιν ἀγαθὸν καὶ ἄλλο χωριζόμενον ἐπιστήμης) (d4-5). Therefore, the conclusion will be that if there is nothing good which knowledge does not encompass, virtue can be nothing but knowledge (d6-8). What let us discuss KG as an epistemological principle for the second Secrates is the relation he tries to establish between knowledge and the Good which, though is alongside with the mentioned thesis and the idea of virtue as knowledge, goes much deeper inside epistemology asking to regard the Good as the basis of knowledge. The effort of Phaedo cannot succeed in establishing the Good as the criterion of explanation and knowledge since, I think, it needs a far more complicated ontology of Republic where Socrates can finally announce KG. What is said in Republic is totally compatible with Phaedo 99d–e and the metaphor of watching an eclipse of the sun. In spite of the fact that we do not have adequate knowledge of the Idea of the Good, it is necessary for every kind of knowledge: 'If we do not know it, even if we know all other things, it is of no benefit to us without it' (505a6-7). The problem of our not having sufficient knowledge of the Idea of Good is tried to be solved by the same method of Phaedo 99d-e, that is to say, by looking at what is like instead of looking at thing itself (506d8-e4). It is this solution that leads to the comparison of the Good with sun in the allegory of Sun (508b12-13). What the Good is in the intelligible realm corresponds to what the sun is in the visible realm; as sun is not sight, but is its cause and is seen by it (b9-10), the Good is so regarding knowledge. It has, then, the same role for knowledge that the sun has for sight. Socrates draws our attention to the function of sun in our seeing. The eyes can see everything only in the light of the day being unable to see the same things in the gloom of night (508c4-6). Without the sun, our eyes are dimmed and blind as if they do not have clear vision any longer (c6-7). That the Good must have the same role about knowledge based on the analogy means that it must be considered as a required condition of any kind of knowledge: -/- The soul, then, thinks (νόει) in the same way: whenever it focuses on what is shined upon by truth and being, understands (ἐνόησέν), knows (ἔγνω) and apparently possesses understanding (νοῦν ἔχειν). (508d4-6) -/- Socrates does not use agathon in this paragraph and substitutes it with both aletheia and to on. He links them with the Idea of the Good when he is to assert the conclusion of the analogy: -/- That which gives truth to the objects of knowledge and the power of knowing to the knower, you must say, is the Idea of the Good: being the cause of knowledge and truth (αἰτίαν δ᾽ ἐπιστήμης οὖσαν καὶ ἀληθείας) so far as it is known (ὡς γιγνωσκομένης μὲν διανοοῦ). (508e1-4) Knowledge and truth are called goodlike (ἀγαθοειδῆ) since they are not the same as the Good but more honoured (508e6-509a5). KG, which had been implicitly contemplated and searched in Phaedo, is now explicitly being asserted in Republic. As what was quoted clearly proves, this principle is the very one which we can observe as the most fundamental principle of the second Socrates in Republic, corresponding to the role KWX had in the first Socrates. The Form of the Good in Republic, of which Santas speaks as 'the centerpiece of the canonical Platonism of the middle dialogues, the centerpiece of Plato’s metaphysics, epistemology, ethics and …' (1983, 256) much more can be said. Plato’s Cave allegory in Book VIII dedicates a similar role to the Idea of the Good. The Idea of the Good is there as the last thing to be seen in the knowable realm, something so important that its seeing equals to understanding the fact that it is the cause of all that is correct and beautiful (517b). Producing both light and its source in visible realm, it controls and provides truth and understanding in the intelligible realm (517c). -/- 2. Tripartite Epistemology BE is thoroughy rejected in the second Socrates and substituted by its opposite, the principle of 'Tripartite Epistemolgy' (TE): -/- TE Opinion is an epistemological status between knowledge and ignorance. BE of the first Socrates was denying any third way besides knowledge and ignorance which was the foundation of Socratic circle without which Socrates could not reject his interlocutors’ possessing any kind of knowledge. We cannot say, however, that the first Socrates had a third epistemological status in mind but rejected it. Such a status was unacceptable for him so that one can say that he would reject any kind of such status if suggested. There were only two possibilities about knowledge: either one knows something or he does not know it. TE, thus, was not the first Socrates’ discovery and, I think it is not the second Socrates’discovery. All we can see in our second group of dialouges is that he uses this principle as an already demonstrated one. Having examined the slave boy in Meno for the prupose of showing the working of recollection, it truns out that he has some opinions in him while he still does not know. Without trying to prove it, Socrates takes this as the distinction between knowledge and opinion: -/- So, he who does not know (οὐκ εἰδότι) about what he does not know (περὶ ὧν ἂν μὴ εἰδῇ) has within himself true opinions (ἀληθεῖς δόξαι) about the same things he did not know (περὶ τούτων ὧν οὐκ οἶδε) (85c6-7). -/- The same distinction is set between ὀρθὴν δόξαν and ἐπιστήμην at 97b5-6 ff. (also cf. 97b1-2: ὀρθῶς μὲν δοξάζων … ἐπιστάμενος). He connects then their difference to the myth of Daedalus, the statue that would run away and escape. So are true opinions, not willing to remain long in mind and thus not worthy until one ties them down by αἰτίας λογισμῷ (98a3-4). Socrates says that this tying down is anamnesis. We face, in Phaedo, the same relation is settled between knowledge as the process of being tied down and getting the capability to give an account, on the one hand, and anamnesis, on the other hand. When a man knows, he must be able to give an account of what he knows (Phaedo 76b5-6) and since not all people are able to give such an account, those who recollect, recollect what once they learned (76c4). Although the distinction between knowledge and opinion is not explicitly used in Phaedo, referring to the parallel link between knowledge plus account and anamnesis in Phaedo and Meno, one can say that those who cannot recollect are not able to give account and, thus, are in a state of opinion. What is said at Phaedo 84a, though not yet a definite distinction between knowledge and opinion, makes a distinction between their objects so as we can agree that it is presupposed. The soul of the philosopher, Socrates says, follows reason, stays with it forever and contemplates the divine, which is not the object of opinoin (ἀδόξαστον) (84a8, cf. Meno 98b2-5). The distinction of knowledge and belief in Republic has a significant difference with what we discussed in Meno and Phaedo since the distinction of Meno was based on anamnesis and thus more an epistemological distinction. Even in Phaedo that we do not have any elaborate discussion about the distinction, the only hint to the matter at 76 is bound to the theory of anamnesis. In addition to the relation of the distinction with this theory, there is another evidence that does not permit us to consider the distinction as an ontological distinction. Let’s see Meno 85c6-7: -/- So, he who does not know about what he does not know has within himself true opinions about the same things he did not know (τῷ οὐκ εἰδότι ἄρα περὶ ὧν ἂν μὴ εἰδῇ ἔνεισιν ἀληθεῖς δόξαι περὶ τούτων ὧν οὐκ οἶδε). (85c6-7) -/- This last sentence persists that the objects of knowledge and true opinion are the same. What Socrates is to say here is that whereas he does not know X he has true opinion about the same X. I think Socrates’ sentence that the slave boy οὐκ εἰδότι ἄρα περὶ ὧν ἂν μὴ εἰδῇ and his restatement of it by saying περὶ τούτων ὧν οὐκ οἶδε is because he wants to emphasize that the slave boy who does not know, has true opinion about the same thing. Socrates could say this just with using τούτων and there would be no necessity to bring περὶ ὧν ἂν μὴ εἰδῇ for οὐκ εἰδότι if he did not want to emphasize. -/- 3. Tripartite Ontology The distinction between knowledge and true opinion in Republic, on other side, has nothing to do with recollection, but is based on an ontological principle, 'Tripartite Ontology' (TO): -/- TO There are things that both are and are not. -/- This principle I confine, among our three dialogues of the second group, to Republic not extended to Meno and Phaedo, is obviously the opposite of BO. Speaking about the lovers of sights and sounds in the fifth book, Socrates distinguishes them from philosophers because their thought is unable to understand the nature of beautiful itself besides beautiful things (476a6-8) and hence they can only have opinions. The philosopher who, on the contrary, believes in beautiful itself and can distinguish it from beautiful things (476c9-d3), has knowledge because he knows, contrasting others who have opinion because they only opine (d5-6). Since those whose knowledge were degraded as opinion will complain about Socrates’ such calling their thought, he provides them the following argument (476e7-477b1): -/- - Does the person who knows, knows (γιγνώσκει) something (τὶ) or nothing (οὐδέν)? - He knows something (τί). - Something that is (ὂν) or is not (οὐκ ὄν)? - Something that is (ὂν) for how could something that is not be known (πῶς γὰρ ἂν μὴ ὄν γέ τι γνωσθείη)? - Then we have an adequate grasp of this: No matter how many ways we examine it, what completely is (παντελῶς ὂν) is completely knowable (παντελῶς γνωστόν) and what is in no way (μὴ ὂν δὲ μηδαμῇ) is in every way unknowable (πάντῃ ἄγνωστον). - A most adequate one. - Good. Now, if anything is such as to be and also not to be (ὡς εἶναί τε καὶ μὴ εἶναι), won’t it be intermediate (μεταξὺ) between what purely is (εἰλικρινῶς ὄντος) and what in no way is (μηδαμῇ ὄντος)? - Yes, it’s intermediate. - Then as knowledge (γνῶσις) is set over what is (τῷ ὄντι), while ignorance (ἀγνωσία) is of necessity set over what is not (μὴ ὄντι) mustn’t we find an intermediate between ignorance (ἀγνοίας) and knowledge (ἐπιστήμης) to be set over the intermediate, if there is such a thing? -/- From the third status of being we must reach to the third status of knowledge. The simple reading of this text can be an existential reading, taking the "is" of the mentioned sentences as existence. The problem is that when it is said that there is something that both is and is not reading "is" existentially, it sounds too bizarre to be acceptable. It cannot easily be understandable to have something as both existent and non-existent at the same time. This problem arose so many debates and led many scholars to reject the existential reading of "is" and suggest some other readings like predicative or veridical readings. I think though Plato’s complicated ontology of Republic cannot be correctly understood by a simple existential reading, this "is" cannot be free from existential sense of being and, thus, cannot be reduced to just a predicative or veridical sense of being. -/- 4. Bound Knowledges In addition to KG, the Good is also the basis of another principle in the second Socrates, namely the principle of 'Bound Knowledge' (BK): -/- BK Knowledge of everything is bound to the knowledge of the Good. -/- We distinguished BK from KG because we want to insist, in BK, on what had not been insisted upon in KG, that is, the binding role that the Good plays in the second Socrates, contrasting the absence of such a role in the first Socrates. Socrates remembers, in Phaedo, his wonderful keen on natural philosophers' wisdom when he was young. The origin of this enthusiasm was Socrates’ hope to know the cause of everything as they used to claim. When he was searching the matters of his interest on their basis, Socrates says, he became convinced he can get no acceptable answer from them and found himself blind even to the things he thought he knew before. One day he hears Anaxagoras’ theory that 'it is Mind that arranges and is the cause of everything (ὡς ἄρα νοῦς ἐστιν ὁ διακοσμῶν τε καὶ πάντων αἴτιος)' (Phd. 97c1-2 cf. DK, Fr.15.8-9, 11-12, 12-14) and thinks that he can finally find what he has always expected, i.e. something which can explain all things. What I intend to show here is that what makes Socrates hopeful is that Anaxagoras’ theory tries 1) to explain all things by one thing and 2) this explanation is understood by Socrates as if it is based on the concept of the Good. That Socrates was searching for one explanation for all things can be proved even from what he has been expecting from natural philosophers. The case is, nonetheless, more clearly asserted when he speaks about Anaxagoras’ theory. In addition to διακοσμῶν τε καὶ πάντων αἴτιος of 97c2 mentioned above, we have τὸ τὸν νοῦν εἶναι πάντων αἴτιον (c3-4) and τόν γε νοῦν κοσμοῦντα πάντα κοσμεῖν (c4-5) all emphasizing on the cause of all things (πάντα) which can clearly prove that one of the reasons which caused Socrates to embrace it delightfully was its claim to provide the cause of all things by one thing. Another reason was that Anaxagoras’ Mind, at least in Socrates’ view, was attempting to explain everything by the concept of the Good. This connection between Mind and Good belongs more to the essential relation they have in Socrates’ thinking than Anaxagoras’ theory because there are almost nothing about such a relation in Anaxagoras. The reason for Socrates’ reading can be that Mind is substantially compatible with Socrates’ idea of the relation between good and knowledge. Both the thesis 'no one does wrong willingly' and the theory of virtue as knowledge we pointed to above are evidences of this essential relation. Nobody who knows that something is bad can choose or do it as bad. The reason, when it is reason, that means when it is as it should be, when it is wise or when it knows, works only based on good-choosing. In this context, when Socrates hears that Mind is considered as the cause of everything, it sounds to him like this: good should be regarded as the basis of the explanation of all things. We see him, thus, passing from the former to the latter without any proof. This is done in the second sentence after introducing Mind: -/- I thought that if this were so, the arranging Mind would arrange all things and put each thing in the way that was Best (ὅπῃ ἂν βέλτιστα ἔχῃ). If one then wished to find the cause of each thing by which it either perishes or exists, one needs to find what is the best way (βέλτιστον αὐτῷ ἐστιν) for it to be, or to be acted upon, or to act. On these premises then it befitted a man to investigate only, about this and other things, what is the most excellent (ἄριστον) and best (βέλτιστον). The same man must inevitably also know what is worse (χεῖρον), for that is part of the same knowledge. (97c4-d5) This passage is a good evidence of Socrates’ leap from Anaxagoras’ Mind to his own concept of the Good that can explain why Socrates found Anaxagoras theory after his own heart (97d7). Mind is welcomed because of its capability for explanation on the basis of good to 'explain why it is so of necessity, saying which is better (ἄμεινον), and that it was better (ἄμεινον) to be so' (97e1-3). What Socrates thought he had found in Anaxagoras can indicate what he had been expecting from natural scientists before. Socrates could not be satisfied with their explanations because they were unable to explain how it is the best for everything to be as it is. It can probably be said, then, that it was the lack of the unifying Good in their explanation that had disappointed him. We must insist that we are discussing what Socrates thought that Anaxagoras’ theory of Mind should have been, not about Anaxagoras’ actual way of using Mind. Phaedo 97c-98b, is not about what Socrates found in Anaxagoras but what he thought he could find in it. On the contrary, it should also be noted that it was not this that was dashed at 98b, but Anaxagoras’ actual way of using Mind. It was Anaxagoras’ fault not to find out how to use such an excellent thesis (98b8-c2, cf. 98e-99b). Socrates gives an example to show how not believing in 'good' as the basis of explanation makes people be wanderers between different unreal explanations of a thing. His words δέον συνδεῖν (binding that binds together) as a description for the Good we chose as the name of BK principle: They do not believe that the truly good and binding binds and holds them together (ὡς ἀληθῶς τὸ ἀγαθὸν καὶ δέον συνδεῖν καὶ συνέχειν οὐδὲν οἴονται). (99c5-6) -/- Having in mind Plato’s well-known analogy of the sun and the Good at Republic 508-509, we can dare to say that his warning of the danger of seeing the truth directly like one watching an eclipse of the sun in Phaedo (99d-e) is more about the difficulty of so-called good-based explanation than its insufficiency, a difficulty which is precisely confirmed in Republic (504e-505a, 506d-e). Moreover, BK is asserted in a more explicit way in the Republic, where the Good is considered not only as a condition for the knowledge of X, as was noted above discussing KG, but also as what binds all the objects of knowledge and also the soul in its knowing them. At Republic VI, 508e1-3, when Socrates says that the Form of the Good 'gives truth to the things known and the power to know to the knower (τοῦτο τοίνυν τὸ τὴν ἀλήθειαν παρέχον τοῖς γιγνωσκομένοις καὶ τῷ γιγνώσκοντι τὴν δύναμιν ἀποδιδὸν)', he wants to set the Good at the highest point of his epistemological structure by which all the elements of this structure are bound. This binding aspect of the Good is by no means a simple binding of all knowledges or all the objects of knowledge, but the most complicated kind of binding as it is expected from the author of the Republic. The kind of unity the Good gives to the different knowledges of different things is comparable with the unity which each Form gives to its participants in Republic: as all the participants of a Form are united by referring to the ideas, all different kinds of knowledge are united by referring to the Good. If we observe Aristotle's assertion that for Plato and the believers of Forms, the causative relation of the One with the Forms is the same as that of the Forms with particulars (e.g. Metaphysics 988a10-11, 988b4), that is to say the One is the essence (e.g., ibid, 988a10-11: τοῦ τί ἐστὶν, 988b4-6: τὸ τί ἢν εἶναί) of the Forms besides his statement that for them One is the Good (e.g., ibid, 988b11-13) the relation between the Good and unity may become more understandable. Since the quiddity of the Good (τί ποτ᾽ ἐστὶ τἀγαθὸν) is more than discussion (506d8-e2), we cannot await Socrates to tell us how this binding role is played. All we can expect is to hear from him an analogy by which this unifying role is envisaged, the sun. The kind of unity that the Good gives to the knowledge and its objects in the intelligible realm is comparable to the unity that the sun gives to the sight and its objects in the visible realm (508b-c). The allegory of Line (Republic VI, 509d-511), like that of the Sun, tries to bind all various kinds of knowledges. The hierarchical model of the Line which encompasses all kinds of knowledge from imagination to understanding can clearly be considered as Plato’s effort to bind all kinds of knowledges by a certain unhypothetical principle. The method of hypothesis starts, in the first subsection of the intelligible realm, with a hypothesis that is not directed firstly to a principle but a conclusion (510b4-6). It proceeds, in the other subsection, to a 'principle which is not a hypothesis' (b7) and is called the 'unhypothetical principle of all things' (ἀνυποθέτου ἐπὶ τὴν τοῦ παντὸς ἀρχὴν) (511b6-7). This παντὸς must refer not only to the objects of the intelligible realm but to the sensible objects as well. Plato does posit, therefore, an epistemological principle for all things, a principle that all things are, epistemologically, bound and, thus, unified by. -/- 5. Bound Beings The ontological aspect of BK we shall call the principle of 'Bound Beings' (BB): -/- BB Being of all things are bound by the Good. -/- We saw in our principle of Split Being (SB) how the first Socrates was criticized because of his approach to split being and separate each thing from other things. The principle of Bound Beings intends to make the things more related, a duty which is done again by the Good. In the allegory of Sun, there are two paragraphs that evidently and deliberately extend the binding role of the Good to the ontological scene: -/- You will say that the sun not only makes the visible things have the ability of being seen but also coming to be, growth and nourishment. (509b2-4) -/- This clearly intends to remind the ontological role the sun plays in bringing to being all the sensible things in order to display how its counterpart has the same role in the intelligible realm (b6-10): -/- Not only the objects of knowledge (γιγνωσκομένοις) owe their being known (γιγνώσκεσθαι) to the Good, but also their existence (τὸ εἶναί) and their being (οὐσίαν) are due to it, though the Good is not being but superior to it in rank and power. That the Good is here represented as responsible for being of things in addition to their being known means, in my opinion, that Plato wants to posit BB in addition to BK. The allegory of Cave at the very beginning of the seventh Book (514aff.) can be taken as another evidence. The role of the Good, one might say, is confined to the intelligible realm because it is asserted that the role the Good plays in this realm is corresponding to that of the sun in the visible realm. The fact that Plato wants to observe the Good also as the ontological cause of the sensible things is obvious from his saying, in the allegory of Cave, that the Form of the Good 'produces light and its source (τὸν τούτου κύριον) [i.e. the sun] in the visible realm' (517c3). We can conclude, then, that the ontological function of the Good is not confined to the intelligible realm in which it is the lord and provides truth and understanding (c3-4) because it is also responsible to produce τὸν κύριον of light. 6. Proportionality of Being and Knowledge Insofaras BE and BO principles of the first Socrates gave way to TE and TO principles of the second Socrates, we cannot expect him to preserve KB in the same way as it was in the first Socrates. The new tripartite ontology and epistemology necessitates some modifications in KB which results in the principle of 'Proportionality of Being and Knowledge' (PBK): -/- PBK To every class of being there is a proportionate category of knowledge. -/- This principle, of course, does not entail the refutation of KB and thus is not kind of rejecting PBK but only a more complicated version of it. Based on PBK, we can still agree that knowledge is of being (KB) but the issue is that since none of the concepts of knowledge and being in the second Socrates are as simple as they were for the first Socrates, we need a more complicated principle for their relation here. Although from Meno 97a where the distinction of knowledge and true opinion is drawn out in the second group of the dialogues, we can expect a new relation, it is articulated in its most complete way in Republic and specifically in the allegory of Line. All the beings are divided there hierarchically to four classes, to each of them belongs a class of knowledge: imagination to images, belief to the sensible things (more correctly: the things of which they[in previous class] were images (ᾧ τοῦτο ἔοικεν)), thought to mathematical objects (?) and understanding to the Forms and the first principle. The degree of clarity that each of the classes of knowledge shares in (σαφηνείας ἡγησάμενος μετέχειν) is proportionate to the degree that its object shares in truth (ἀληθείας μετέχει). (511e2-4) -/- Conclusion From the six onto-epistemilogical principles of the first Socrates, four principles turn to their opposite in the middle period dialogues. While bipolar epistemology and ontology of the early dialogues give place to tripartite epistemology in the middle period dialogues and tripartite ontology in Republic, the split knowledge and being of the first Socrates are inclined to be substituted by bound knowledges and bound beings in the second Socrates and specifically in Republic. Not all our system of principles in this article is necessarily determinative. Either they are rightly formulated or not, our result would not be vulnerable if we accept that 1) making the distinction of knowledge and belief, 2) accepting the being of not being and 3) trying to bind both being and knowledge by the concept of the Good happens only in middle period dialogues, having been absent in the early ones. These are the favourite results all those somehow arbitrary and even oversimplified principles were to illustrate; that there is kind of a development in the epistemological as well as the ontological grounds of Plato’s philosophy. -/- Notes . (shrink)

FISIOLOGIA DO PARTO E DA LACTAÇÃO ANIMAL -/- ANIMAL REPRODUCTION: PHISIOLOGY OF PARTURITION AND ANIMAL LACTATION -/- Emanuel Isaque Cordeiro da Silva Departamento de Zootecnia da UFRPE WhatsApp: (82)98143-8399 -/- 1. INTRODUÇÃO O sucesso biológico do processo de reprodução culmina com a sobrevivência das crias. Durante a gestação, o feto desenvolve-se no útero materno protegido das influências externas, e obtendo os nutrientes e o oxigênio através da mãe. O parto é o processo biológico que marca o fim da gestação e (...) o início da vida extrauterina do animal. Para garantir a sobrevivência do recém-nascido o parto deve ser um processo controlado para que se inicie unicamente quando o feto tiver alcançado desenvolvimento suficiente que lhe permita enfrentar a vida extrauterina. Após o nascimento, a secreção de leite pela glândula mamária proporciona ao neonato tanto os nutrientes necessários para seu desenvolvimento como as defesas (imunoglobulinas) que lhe protegerão contra as possíveis infecções durante as primeiras fases de sua vida. Parto e lactação constituem a última etapa de um ciclo reprodutivo completo nas fêmeas dos animais domésticos, estando ambos os processos regulados e sincronizados por complexas mudanças hormonais na mãe. Estas mudanças são, em última análise, provocadas e governadas pelo próprio feto ou recém-nascido, o qual acomoda as respostas maternas às suas necessidades garantindo a sua sobrevivência. 2. O PARTO O parto é definido como o processo fisiológico pelo qual ocorre a expulsão de um ou mais fetos maduros, bem como das membranas fetais existentes no útero materno. Este processo é desencadeado por uma interação complexa entre as hormonas maternas (fatores maternos) e fetais (fatores fetais). Para que se realize a expulsão do feto é necessário que o útero deixe de ser um órgão quiescente, essencial para a manutenção da gestação, para ser um órgão contrátil. Ao mesmo tempo, o cérvix ou colo uterino, que durante a gestação permanece firmemente fechado para impedir a expulsão prematura do feto e evitar a entrada de agentes infecciosos, relaxa e dilata para facilitar a passagem do feto na hora do parto. Esta modificação na atividade do útero e do colo uterino, ocorrem como consequência das mudanças hormonais que o organismo materno experimenta à medida que a data do parto se aproxima. 2.1 Fatores maternos A gestação dos animais domésticos ocorre com elevada concentração de progesterona que, dependendo da espécie animal, é secretada seja pelo corpo lúteo do ovário (vaca, porca e cabra) ou pela placenta (ovelha e égua). A progesterona desempenha um papel fundamental durante a gestação, inibindo as contrações da musculatura lisa do útero (miométrio), permitindo assim a acomodação do feto durante o seu crescimento. Os estrogênios, estimulantes da atividade contrátil do miométrio, mantêm-se a baixas concentrações durante a maior parte da gestação. À medida que se aproxima o momento do parto, os níveis destes hormônios esteroides modificam-se, produzindo-se a diminuição nos níveis circulantes da progesterona ao mesmo tempo que se incrementam os valores sanguíneos dos estrogênios (figura 1). A redução dos níveis de progesterona suprime a sua ação inibitória sobre a atividade contrátil do miométrio, permitindo que se manifestem os efeitos estimulantes dos estrogênios sobre este órgão. A concentração de estrogênios começa a aumentar geralmente no final da gestação, atingindo os seus valores máximos no momento do parto (figura 1). O aumento da concentração de estrogênios favorece a atividade contrátil espontânea do útero ao: a) estimular a síntese de proteínas contráteis; b) aumentar, sob medida, a sensibilidade do miométrio uterino à ação estimulante das prostaglandinas; c) induzir a formação de receptores de oxitocina no útero. -/- Figura 1. Níveis de progesterona e estrógenos durante a gestação e parto das espécies ovina, caprina, suína e bovina. Fonte: HAFEZ, 2013. Os estrogênios estimulam a síntese e secreção de prostaglandina (PGF2a), que constitui o elemento essencial para o início do parto devido aos efeitos que esta substância provoca. Assim, nas fêmeas, cujos níveis de progesterona gestacional dependem da presença do corpo lúteo, a secreção de PGF, origina a regressão deste (luteólise), com a consequente diminuição da progesterona a níveis basais. Além disso, a PGF2a origina contrações de crescente intensidade no útero sensibilizado pela ação dos estrogênios. Esta ação contrátil da PGF2a deve-se a um aumento da concentração de cálcio intracelular das fibras musculares uterinas. A PGF2a também está envolvida no relaxamento do colo do útero, inibindo a formação de colágeno cervical ao mesmo tempo que estimula a síntese de enzimas (colagenase) que degradam a matriz de colágeno formado no início da gestação. A dilatação do colo do útero está também associada à pressão que o feto exerce sobre o mesmo e, no caso da porca, a relaxina pode também estar envolvida. Esta hormona é também de grande importância para a preparação do parto em todas as espécies animais, uma vez que é responsável pelo relaxamento dos ligamentos e músculos que rodeiam o canal pélvico para favorecer a separação da sínfise púbica durante a expulsão do feto. Nos grandes animais (vaca, égua) as mudanças que ocorrem nos tecidos e ligamentos pélvicos são muito evidentes e constituem um sintoma de parto iminente. O início do parto, ou primeira fase do parto, caracteriza-se pelo aumento das contrações uterinas provocadas pela PGF2a coincidindo com a dilatação do colo uterino para permitir a passagem do feto para o canal do parto, momento em que começa a segunda fase do parto. A distensão vaginal que produz-se para a passagem do feto pelo canal do parto origina um estímulo nervoso que viaja através da medula espinal para o hipotálamo, onde se encontram os neurônios responsáveis pela síntese de oxitocina. As terminações nervosas destes neurónios são projetadas para o lobo posterior da hipófise (neurohipófise), onde a oxitocina é secretada para ser, posteriormente , transportada pela circulação sanguínea. Este reflexo neuroendócrino chamado reflexo de Ferguson determina a secreção súbita de oxitocina, provocando o aumento tanto na intensidade como na frequência das contrações uterinas necessárias para a expulsão final do feto. O papel da oxitocina é ativar a conclusão do processo de expulsão, uma vez que esta hormona não está envolvida no início do parto. A alteração mais significativa entre a gestação e o parto é a alteração na atividade contrátil do miométrio uterino. Esta mudança é devido às alterações hormonais que ocorrem na mãe quando a gestação chegou a fim. No entanto, para que estes mecanismos maternos sejam acionados, é necessário que o feto indique de alguma forma à mãe o seu estado de desenvolvimento, de modo que o nascimento realize-se quando o feto estiver preparado para enfrentar a vida extrauterina. 2.2 Fatores fetais A destruição experimental da hipófise e/ou das glândulas adrenais do feto origina o prolongamento da gestação nos animais domésticos. Pelo contrário, a administração exógena de cortisol (corticosteroides adrenais), ou do seu precursor hipofisário (ACTH), à circulação fetal provoca, em poucas horas, o início do parto. Estes fatos evidenciam a importância do eixo hipófise-adrenal do feto para desencadear o início do parto (figura 2). Figura 2. Mecanismos fetais que controlam o parto em ovelhas. Fonte: LIGGINS et al, 1972. No final da gestação, o feto maduro apresenta um aumento da concentração de corticosteroides plasmáticos devido ao efeito estimulante da hormona adrenocorticotróide (ACVH) secretada pela hipófise fetal sobre as glândulas adrenais do feto. Os corticosteroides fetais por sua vez estimulam as enzimas placentárias para transformar a progesterona em estrogênio. O resultado final é a diminuição dos níveis de progesterona ao mesmo tempo que se eleva a concentração de estrogênios que, por sua vez, estimulam a libertação de PGF2a responsável pelas contrações uterinas. Este raciocínio explica algumas doenças caracterizadas por gestação prolongada em ovelhas, como ocorre na África do Sul, onde estes animais são obrigados, durante as épocas de seca, a ingerir as folhas de um arbusto chamado Salsola tuberculate. O prolongamento da gestação ocorre quando estas folhas são ingeridas durante o último terço da gestação cujos efeitos estão relacionados com a supressão do eixo hipotálamo-hipófise, com o qual as adrenais não recebem o estímulo necessário (ACTH) para a síntese e liberação de corticoides. O efeito contrário é observado nas cabras da raça Angorá, nas quais se produzem, com relativa frequência, partos prematuros que podem estar relacionados com um desenvolvimento precoce das glândulas adrenais. Isto significa que, nos animais domésticos, o feto determina a data do parto. O sinal hormonal que indica à mãe o grau de maturidade do feto é o desenvolvimento do eixo hipotálamo-hipófise-adrenal que origina o aumento na secreção de corticoides fetais que são os responsáveis por desencadear as alterações hormonais no organismo materno necessárias para iniciar o parto. A figura 2 mostra como a remoção da hipófise e as adrenais do feto prolongam a gestação, enquanto a administração exógena de ACTH ou corticoides (cortisol) ao feto originam um parto prematuro. O momento em que ocorre o aumento da concentração plasmática de corticoides no feto varia de acordo com a espécie: de 25 a 30 dias antes do parto na vaca, de 7 a 10 dias na porca e de 2 a 3 dias na ovelha. 2.3 Desenvolvimento e fases do parto O parto inicia-se com o início das contrações peristálticas e regulares do miométrio uterino ao mesmo tempo que o colo do útero se dilata progressivamente. Nas fêmeas que gestam um único feto (monotecas), as contrações começam na extremidade anterior do córneo uterino, enquanto que nas espécies que gestam vários fetos (politocas) as contrações começam pela extremidade cervical para começar a expulsar o feto que se encontra mais próximo do cérvix. Durante o parto são reconhecidas três fases: 1. Fase preparatória - Na qual as contrações uterinas estimulam a rotação do feto (fêmeas monotecas) para adotar a posição dorsal (extremidades anteriores e cabeça forçadas contra o cérvix) que lhe permite oferecer a menor resistência para sua expulsão. A PGF2a provoca as contrações miometriais e a dilatação do cérvix, deslocando o feto contra e através desta estrutura. 2. Fase de expulsão - A passagem do feto através do colo uterino e da vagina causam a completa dilatação destas estruturas, originando a secreção de oxitocina (reflexo de Ferguson), que provoca contrações de maior frequência e intensidade. Por sua vez, estas contrações uterinas são reforçadas pela pressão e contração dos músculos abdominais, chegando estes últimos a ser a força principal (forças de expulsão) envolvida no processo de expulsão do feto. O cordão umbilical rompe-se bem ao levantar-se a mãe ou pelos movimentos do recém-nascido. 3. Fase de expulsão da placenta - Após o parto, as contrações rítmicas do útero continuam a facilitar a expulsão da(s) placenta(s). O tempo necessário para este processo varia de acordo com a espécie animal. Este processo é rápido na égua, já que a separação do corion (membrana fetal) de sua inserção uterina ocorre durante a expulsão do feto, com o qual o parto deve ser concluído rapidamente ou, caso contrário, o potro se asfixiaria. Nos ruminantes, a expulsão da placenta cotiledonaria é um processo mais lento que exige a separação dos cotilédones (membrana fetal) das carúnculas do útero. Por conseguinte, a troca de nutrientes e oxigênio entre a mãe e o feto continua até que este tenha sido totalmente expelido, devido ao cordão umbilical destes animais ser bastante longo. Nas fêmeas politocas, como a porca, geralmente as placentas de vários leitões são expulsadas no final, quando os leitões já foram expelidos, se bem que o último leitão poderá ser expelido durante a expulsão da massa placentária. 3. LACTAÇÃO A lactação constitui o processo que define os mamíferos como classe biológica. O desenvolvimento pós-natal dos mamíferos vai depender, em grande medida, dos nutrientes e defesas fornecidos pela mãe através da secreção de leite (imunoglobulinas). Assim, uma vez concluído o desenvolvimento gestacional do feto, a glândula mamária irá substituir, de certa forma, a função nutritiva e protetora da placenta durante a gestação. 3.1 Anatomia funcional da glândula mamária A estrutura funcional da glândula mamária é muito semelhante em todos os mamíferos, embora o tamanho, forma e número de glândulas varia dependendo da espécie animal. As glândulas mamárias desenvolvem-se como estruturas pares cujo número varia de um par (égua, cabra e ovelha), dois pares (vaca) até sete ou nove (porca). A localização das glândulas também difere sendo inguinal em vaca, égua, cabra e ovelha, enquanto que na porca, cadela e gata se estendem por todo o comprimento do tórax e abdômen. Nos animais domésticos em geral as glândulas mamárias recebem o nome de úberes. Tomando como modelo a vaca, a glândula mamária se organiza em duas estruturas: o estroma, formado por tecido conjuntivo procedente dos ligamentos suspensório medial, localizado entre os dois pares de glândulas, dando suporte à segunda estrutura que é o tecido secretor. Este é formado por acúmulos de células secretoras formando estruturas ocas chamadas alvéolos, que são as unidades fundamentais secretoras de leite. Os alvéolos estão circulados internamente por células epiteliais (secretoras) e rodeados externamente por células mioepiteliais contráteis, cuja contração origina a ejeção do leite (figura 3). O agrupamento de vários alvéolos adjacentes formam um lobo secretor. Figura 3. Diagrama de um agregado de alvéolos na glândula mamária de uma cabra. Fonte: COWIE et al, 1980. Os lobos expelem a secreção através de ductos que, por sua vez, drenam os ductos galactóforas (ductos lácteos) de maior diâmetro, para desembocar em áreas especializadas em armazenar o leite chamadas cisternas (vaca, cabra). Finalmente, a cisterna abre-se para o exterior através do canal papilar da teta. A presença do músculo liso na teta permite-lhe agir como esfíncter para impedir que o leite seja expelido passivamente do interior da glândula. O mamilo/teta é provido de numerosos receptores sensitivos cuja excitação durante a ordenha ou amamentação vai desencadear estímulos nervosos de grande importância para a manutenção da lactação. 3.2 Desenvolvimento da glândula mamária (mamogênese) A glândula mamária difere das demais glândulas do organismo no escasso desenvolvimento que apresenta no nascimento da fêmea, o qual não se inicia até que esta não atinja a puberdade. O início da atividade cíclica do ovário (puberdade) dá origem à síntese de estrogênios (fase folicular do ciclo estral) e progesterona (fase lútea). Os estrogênios originam o alongamento e ramificação dos ductos e a formação de pequenas massas esféricas de células (os futuros alvéolos). Embora este desenvolvimento seja dependente do estrogênio, é também necessária a ação sinérgica da prolactina, hormona do crescimento (GH) e corticoides adrenais, como demonstrado pelos estudos realizados em ratos aos quais foi removida a hipófise, glândulas suprarrenais e ovários (figura 4). A função da progesterona no desenvolvimento da glândula mamária é estimular o crescimento do lobo-alveolar, mas como no caso anterior também requer a ação conjunta dos hormônios acima mencionados. Figura 4. Hormonas relacionadas com o crescimento da glândula mamária e início da secreção de leite na rata hipofisectomizada-adrenoectomizada-ovariectomizada. Fonte: COWIE, 1980. O desenvolvimento da glândula, durante cada ciclo estral, vai depender da duração da fase folicular (níveis elevados de estrogênio), já que nas restantes fases do ciclo, quando os níveis de estrogênio são baixos, os ductos sofrem uma ligeira regressão. Nas espécies com ciclos curtos (rata), em que a fase folicular do ciclo é predominante, enquanto a fase lútea é quase inexistente, verifica-se um grande desenvolvimento dos ductos; enquanto que aquelas que apresentam um corpo lúteo funcional de longa duração (cadela e primatas), além do crescimento dos ductos, mostram um grande desenvolvimento lóbulo-alveolar semelhante ao que ocorre na gestação. É durante a gestação que o sistema alveolar sofre uma hipertrofia considerável, resultando em lobos proeminentes e no desenvolvimento da luz interna dos alvéolos, fato que é evidente na maioria dos animais domésticos por volta da metade do período gestacional. Em algumas espécies, as células que circundam interiormente os alvéolos contêm produtos secretores, indicando que a glândula mamária já está preparada para a fase da lactação. O desenvolvimento glandular durante a gestação deve-se ao efeito conjunto da progesterona e dos estrogênios com as hormonas hipofisárias acima mencionadas: prolactina, hormona do crescimento (GH) e adrenocorticotropina (ACTH). A proporção entre estrogênios e progesterona varia de acordo com a espécie, mas geralmente é necessária uma maior concentração de progesterona (proveniente do corpo lúteo ou da placenta). Quanto às hormonas hipofisárias, a prolactina desempenha um papel fundamental na diferenciação da glândula mamária (mesmo a baixas concentrações) ao estimular o desenvolvimento do epitélio secretor dos alvéolos. A GH favorece o crescimento dos ductos e a ACTH estimula a secreção de corticoides nas adrenais que, por sua vez, favorecem de forma generalizada o crescimento das glândulas. 3.3 Secreção da glândula mamária (lactogênese) A lactogênese, ou o processo pelo qual se produz a síntese e secreção do leite pela glândula mamária, começa no final da gestação coincidindo com o desencadeamento do parto. O primeiro leite formado imediatamente antes ou depois do parto é denominado colostro. No entanto, a lactação não pode desenvolver- se completamente até que se inicie o processo de parto. Isto deve-se ao fato de que o processo de lactação resulta de uma interação complexa de hormonas que preparam a glândula mamária para a secreção do leite. Os requisitos hormonais mínimos para o início da lactogênese são: aumento da secreção de estrogênios, prolactina e corticoides, juntamente com a diminuição da concentração de progesterona, perfis hormonais que estão intimamente relacionados com o desencadeamento do parto. Isto deve-se ao fato de que a progesterona inibe a atividade lactogênica da prolactina bloqueando a formação dos seus receptores na glândula mamária durante a gestação impedindo, assim, a prolactina de sintetizar os componentes fundamentais do leite. Pelo contrário, o aumento da concentração de estrogênios no final da gestação (figura 1, na seção do parto) estimula a síntese, o armazenamento e a secreção hipofisária de prolactina. Assim, apesar da glândula mamária estar preparada para iniciar a secreção de leite, muito antes da data prevista para o parto, a elevada concentração de progesterona (existente durante esse período de gestação) impede a fase láctea (saída do leite pelas tetas) de ocorrer antes da expulsão do feto. Desta forma, o feto poderá beneficiar das vantagens que o fornecimento do colostro materno irá trazer para a sua sobrevivência (imunização, nutrição e favorecimento da exoneração do mecônio). O aumento da concentração de estrogênios nos dias que antecederem o parto resulta num rápido aumento das concentrações plasmáticas de prolactina e corticoides. A prolactina é a hormona lactogênica mais importante na síntese dos componentes do leite. No entanto, para que esta hormona possa exercer a sua função, é necessária a participação dos corticoides, já que os mesmos são os responsáveis pelo desenvolvimento das organelas citoplasmáticas (retículo endoplasmático rugoso e aparelho de Golgi) onde se realiza a síntese do leite. No desenvolvimento da lactogênese, para além da prolactina e dos corticoides, participam também outras hormonas como a insulina, a tiroxina e o hormônio do crescimento. A insulina estimula a proliferação de novas células epiteliais na glândula mamária, enquanto a tiroxina, embora não seja essencial para a lactação, pode influenciar no volume de leite produzido pela fêmea (alta produção leiteira). Por último, a hormona do crescimento favorece, em geral, a lactação, existindo atualmente um interesse considerável no uso desta hormona para promover a produção adicional de leite em vacas através da sua administração exógena (trabalho e projeto desenvolvido pela professora titular e médica-veterinária do IFPB Campus Sousa Marianne Christina Velaqua). 3.3.1 Síntese e secreção dos componentes do leite Os principais constituintes do leite são: proteínas (caseína, alfa-lactalbumina, albumina sérica e imunoglobulinas), açúcares (lactose), gorduras (principalmente sob a forma de triglicerídeos), vitaminas, minerais e citrato (no caso dos ruminantes). As proteínas (caseína e alfa-lactalbumina) são sintetizadas no retículo endoplasmático rugoso e posteriormente embaladas em vesículas secretoras do aparelho de Golgi para serem liberadas da célula para a luz alveolar mediante um processo de exocitose. A lactose é o principal açúcar do leite que, além disso, atua regulando a pressão osmótica do mesmo de modo que o volume de leite que a glândula mamária segrega está diretamente relacionado com a quantidade de lactose presente. A síntese da lactose ocorre no aparelho de Golgi pela condensação de glicose e galactose; esta reação é catalisada por uma enzima (lactose sintetase) presente na membrana do aparelho de Golgi que, por sua vez, é ativada pela proteína alfa-lactalbumina. Esta proteína só aparece na glândula mamária e é essencial para a síntese da lactose, o que demonstra que este açúcar é exclusivamente formado no leite. A lactose é também embalada junto com o cálcio, o fosfato e as proteínas nas vesículas secretoras para ser expulsada ao lúmen alveolar por exocitose. As imunoglobulinas (anticorpos IgA) são formadas pelas células plasmáticas, derivadas dos linfócitos B do sangue, como consequência da exposição da mãe a diferentes microrganismos. Estes anticorpos passam para a glândula mamária por migração dessas células a partir dos tecidos adjacentes. Os triglicerídeos são sintetizados no citoplasma e no retículo endoplasmático liso a partir de ácidos graxos provenientes da circulação sanguínea; em seguida, unem-se formando glóbulos de gordura que se dirigem até o vértice da membrana plasmática para serem finalmente expelidos para a luz do alvéolo, rodeados pela membrana, formando assim uma dispersão de glóbulos de gordura (figura 5). Figura 5. Estrutura de três células alveolares durante a síntese do leite. Fonte: COWIE, 1980. Do ponto de vista quantitativo, a caseína e os triglicerídeos constituem as proteínas e as fontes de energia, respectivamente, mais importantes do leite. Por último, o citrato é um intermediário do metabolismo da glicose que ocorre em grande concentração no leite dos ruminantes. Este composto é também englobado no interior das vesículas secretoras, junto com os outros compostos, para sua expulsão à luz alveolar. A composição do leite varia dependendo da espécie animal, e difere também até entre a mesma espécie. Estas variações estão relacionadas com a raça, idade, estágio de lactação e estado nutricional do animal. O teor de gordura no leite de ovelhas, porcas, cadelas e gatas varia entre 7 e 10%. No gado leiteiro estes valores variam de 3,5 a 5,5%, dependendo da raça. Em relação às cabras, os valores de gordura são muito semelhantes aos das vacas, enquanto o leite das éguas é o que tem menor teor de gordura (tabela 1). Espécie Gordura Proteína Lactosa Cinzas/Cálcio Gata 7,1 10,1 4,2 0,5 Vaca holandesa 3,5 3,1 4,9 0,7 Cadela 9,5 9,3 3,1 1,2 Cabra 3,5 3,1 4,6 0,8 Égua 1,6 2,4 6,1 0,5 Tabela 1. Composição do leite em várias espécies (%). Fonte: JACOBISON, 1984. 3.4 Manutenção da lactação (galactopoiese) A capacidade da glândula mamária de secretar um grande volume de leite começa em/ou imediatamente antes do parto, para aumentar no período pós-parto durante um tempo variável e, posteriormente, diminuir de forma gradual. Em geral, existe um paralelismo entre a atividade secretora da glândula e a procura de leite por parte do lactente. Isto deve-se ao fato de sucção pelo lactente, ou a extração por ordenha, que constituem o fator fundamental para a manutenção da lactação. A sucção estimula a lactação de duas formas: a) reduzindo os efeitos inibitórios da pressão intramamária produzida pela acumulação de leite, e b) estimulando intensamente a secreção de hormonas necessárias para manter a síntese e secreção de leite nos alvéolos. As hormonas que desempenham um papel fundamental na manutenção da lactação são: I) a prolactina, que é responsável pela estimulação da síntese e secreção de leite nas células epiteliais nos alvéolos, e 2) a oxitocina, que provoca a contração das células musculares que circundam externamente os alvéolos e os ductos (células mioepiteliais). A libertação de ambos os hormônios ocorre como resultado de um reflexo neuroendócrino originado pela estimulação do mamilo. 3.4.1 Secreção reflexa de prolactina A secreção de prolactina é regulada por dois fatores hipotalâmicos: a dopamina, que inibe a secreção de prolactina e um fator cuja identidade não está bem definida, conhecido como fator liberador de prolactina (PRF)que estimula a liberação deste hormônio. O estímulo sensorial originado como sequência da estimulação do mamilo, pela sucção do lactente, é transportado através da medula espinhal para o hipotálamo, onde atua na inibição da dopamina ou estimulando a secreção do PRF para desencadear a secreção de prolactina da adenohipófise para a circulação sanguínea (figura 6). Figura 6. Reflexos neuroendócrinos secretores de prolactina e oxitocina. Fonte: HAFEZ, 2000. A prolactina estimula a secreção dos componentes do leite para a luz dos alvéolos, afim de repor o volume de leite extraído durante a última ordenha ou sucção. Ao mesmo tempo, a prolactina induz a síntese das proteínas, incluindo a alfa-lactalbumina para estimular novamente a síntese da lactosa, bem como as enzimas necessárias para a produção dos triglicerídeos. Desta forma, a secreção de prolactina originada pelo lactente durante o aleitamento proporciona um mecanismo simples para combinar o volume de produção de leite com as necessidades do lactente. A quantidade de prolactina liberada durante cada período de sucção depende do número de crias, da duração do estímulo e dos intervalos de tempo decorridos entre os períodos de sucção (ou ordenha). No caso das vacas leiteiras, as ordenhas são geralmente realizadas de doze em doze horas, intervalo de tempo suficiente para manter a lactogênese. Os valores plasmáticos de prolactina aumentam imediatamente após o início da ordenha, mas os valores mais elevados são obtidos cerca de meia hora após o início do estímulo (ordenha ou sucção). A secreção de prolactina e a produção de leite são influenciadas de alguma forma pelo fotoperíodo, uma vez que, em alguns animais se comprovou como o aumento do número de horas de exposição à luz dá origem a um aumento da concentração de prolactina circulante, bem como uma maior produção de leite (entre 6 e 10%) (trabalho e projeto elaborado pelos estudantes do curso técnico em agropecuária e da graduação em Medicina Veterinária do IFPB Campus Sousa sob a coordenação e orientação da profa. Me. Esp. Marianne C. Velaqua). 3.4.2 Reflexo da ejeção do leite A sucção do mamilo pelo lactente estimula os receptores sensoriais presentes nesta estrutura, originando a geração de impulsos nervosos que são transmitidos pelas vias nervosas ascendentes da medula espinhal para os corpos celulares produtores de oxitocina no hipotálamo. O estímulo desencadeia a síntese e liberação de um bolo de oxitocina através das terminações nervosas dos núcleos hipotalâmicos para a neurohipófise, da qual é transmitida, através do sangue, para a glândula mamária, provocando a contração das células mioepiteliais que rodeiam os alvéolos (figura 6). Além da estimulação direta do mamilo provocada pela sucção, qualquer estímulo relacionado à ordenha é capaz de gerar o reflexo da ejeção, por exemplo: os estímulos sensoriais auditivos (ruído dos cubos na hora da ordenha), visuais (ambiente da sala de ordenha), táteis (lavagem manual dos mamilos antes da ordenha) e os estímulos olfatórios que se produzem em torno do animal. O desencadeamento do reflexo de ejeção pelos estímulos sensoriais, que não estão diretamente relacionados com a sucção ou ordenha, indica a possível participação de centros superiores do sistema nervoso central para controlar a secreção de oxitocina. Esta teoria é baseada em que os estímulos relacionados com situações de estresse em animais de estimação (medo, ansiedade, frio, etc.) inibem a ejeção do leite. A contração das células mioepiteliais gera um aumento da pressão intra-alveolar mamária, provocando o deslocamento do leite para os ductos maiores da glândula. Este efeito é popularmente conhecido como diminuição do leite e constitui um mecanismo fisiológico muito eficaz para controlar a expulsão do leite para o mamilo, assegurando que a ejeção do leite se realize unicamente quando o lactente o demanda. O efeito estimulante da oxitocina é de grande importância já que a maior parte do leite se encontra nos alvéolos e nos ductos, com o qual, a ausência deste hormônio provocaria um lento movimento do leite para a cisterna do úbere e, portanto, uma menor quantidade de leite. Assim, quando os alvéolos e ductos menores são contraídos, ocorre o relaxamento dos ductos principais, bem como da cisterna (ruminantes) e do mamilo, o que dá origem a um aumento destas estruturas para alojar o volume de leite expelido. Como resultado da volumosa ejeção do leite dos alvéolos e ductos menores, ocorre um aumento da pressão intramamária de modo que o lactente terá que vencer a resistência do esfíncter do mamilo para poder extrair o leite. A produção de leite pela glândula mamária diminui gradualmente à medida que os intervalos de tempo entre os dois períodos de amamentação do lactente diminuem e os estímulos necessários para manter as concentrações de prolactina e oxitocina na circulação sanguínea. A diminuição ou cessação da secreção de leite, geralmente coincide com a mudança na alimentação das crias (desmame) para passar à dieta característica da espécie. 3.5 Colostro O colostro é o primeiro leite que se forma na glândula mamária coincidindo com o parto. A ingestão de colostro por recém-nascidos é de grande importância para a sua sobrevivência, não só pelo seu elevado valor nutritivo, mas também pelo seu teor em imunoglobulinas (IgA) que lhe confere a imunização passiva necessária para o proteger contra patologias. Em algumas espécies (homem, coelho e cobaia) grande parte dos anticorpos passam para a circulação do feto através da placenta durante a gestação. Nos animais domésticos (vaca, égua, ovelha, cabra, porco) as características da placenta (número de camadas entre a circulação materna e fetal) não permitem a passagem destas proteínas. Como resultado, a imunização das crias nestas espécies animais vai depender da transferência das imunoglobulinas através do colostro. O epitélio intestinal dos recém-nascidos permite a passagem destas imunoglobulinas durante as primeiras 24 a 48 horas de vida. Passado este tempo, o epitélio torna-se impermeável à passagem dos anticorpos, fato que põe em evidência a importância que tem para os animais recém-nascidos e desprovidos de defesas a ingestão do colostro durante os primeiros dias. A composição do colostro caracteriza-se (em relação ao leite normal) por um teor mais elevado de proteínas, vitaminas, minerais e uma menor concentração de lactose. A composição do colostro muda gradualmente durante os primeiros três dias após o parto para se transformar em leite normal. 4. RESUMO E PRIMEIRAS CONCLUSÕES O parto, ou processo fisiológico pelo qual se expulsa o feto, é o resultado da maturação sequencial de um sistema de comunicação hormonal. A sequência inicia-se no sistema nervoso central do feto de onde os sinais são transmitidos e amplificados, através da hipófise, para as glândulas adrenais fetais, as quais respondem ao estímulo mediante a secreção de cortisol. O aumento da concentração de cortisol por parte do feto indica que este conseguiu o desenvolvimento necessário para enfrentar a vida extrauterina e, portanto, é hora de interromper a gestação. O cortisol atua sobre a placenta para aumentar a secreção de estrogênios que, por sua vez, estimulam a síntese e a liberação de prostaglandinas. O resultado é a diminuição da progesterona, que é a hormona encarregada de manter a gestação ao inibir as contrações espontâneas do útero, impedindo assim a expulsão prematura do feto. O útero, sob os efeitos da prostaglandina, começa a contrair-se ao mesmo tempo que o colo uterino amolece e dilata progressivamente (fase preparatória do parto). A passagem do feto ao canal do parto origina a secreção reflexa de oxitocina (fase de expulsão), causando contrações de maior frequência e intensidade que culminam com a expulsão do feto. Finalmente, as contrações uterinas continuam durante algum tempo até que finalmente é expulsa a placenta (fase de expulsão da placenta). O desenvolvimento da glândula mamária durante a gestação e a subsequente capacidade desta estrutura para secretar leite, coincidindo com o parto, oferece aos animais pertencentes à classe biológica dos mamíferos a vantagem de alimentar as suas crias para assegurar a sua sobrevivência durante as primeiras fases do seu desenvolvimento e, portanto, a continuidade da espécie. A lactação constitui um dos processos fisiológicos mais complexos em consequência do grande número de hormonas que, segregadas de forma coordenada, controlam as diferentes fases pelo que atravessa este processo: I) mamogênese ou desenvolvimento dos dutos e estruturas lóbulo-alveolares durante a gestação; 2) lactogênese ou síntese láctea por células epiteliais e sua secreção para a luz alveolar coincidindo com o parto, e 3) galactopoiese ou manutenção da síntese e secreção do leite como consequência da sua extração da glândula mamária seja pela sucção da cria ou pela ordenha. -/- Emanuel Isaque Cordeiro da Silva – Departamento de Zootecnia da UFRPE. Recife, 2020. -/- REFERÊNCIAS BIBLIOGRÁFICAS -/- BEIGHLE, D. E. The effect of gestation and lactation on bone calcium, phosphorus and magnesium in dairy cows. Journal of the South African Veterinary Association, v. 70, n. 4, p. 142-146, 1999. BRACKELL, B. G.; JR SEIDEL, G. E.; SEIDEL, S. Avances en zootecnia nuevas técnicas de reproducción animal. Zaragoza: Acribia, 1988. COLE, H. H.; CUPPS, P. T. Reproduction in domestic animals. 1ª ed. Londres: Academic Press, 1977. COWIE, Alfred T.; FORSYTH, Isabel A.; HART, Ian C. Lactation. In: Hormonal control of lactation. Springer, Berlin, Heidelberg, 1980. p. 146-229. CUNNINGHAM, James G. Fisiología veterinaria. São Paulo: Elsevier, 2003. DERIVAUX, Jules; BARNABÉ, Renato Campanarut. Reprodução dos animais domésticos. Zaragoza: Acribia, 1980. DA SILVA, Emanuel Isaque Cordeiro. Definição de Conceitos Básicos na Reprodução Animal: Fertilidade, Fecundidade e Prolificidade-Suínos. Philarchive. Disponível em: -----. Acesso em: Fevereiro de 2020. DA SILVA, Emanuel Isaque Cordeiro. Características Gerais dos Bovinos/General Characteristics of Cattle Bovine. Philarchive. Disponível em: -----. Acesso em: Fevereiro de 2020. DA SILVA, Emanuel Isaque Cordeiro. Reprodução Animal: Fecundação e Gestação. Disponível em: Acervo IFPE. Acesso em: Março de 2020. FERNÁNDEZ ABELLA, Daniel Héctor. Principios de fisiología reproductiva ovina. Montevidéu: Hemisferio Sur1993. GONZÁLEZ, Félix HD. Introdução a endocrinologia reprodutiva veterinária. Porto Alegre: UFRGS, v. 83, 2002. HAFEZ, E. S. E.; HAFEZ, B. Reprodução animal. São Paulo: Manole, 2004. HAFEZ, Elsayed Saad Eldin; HAFEZ, B. (Ed.). Reproduction in farm animals. Nova Jersey: John Wiley & Sons, 2013. HUNTER, R. H. F. Reproducción de los animales de granja. Zaragoza: Acribia, 1987. HUNTER, Ronald Henry Fraser et al. Physiology and technology of reproduction in female domestic animals. Londres: Academic Press, 1980. ILLERA, M. Endocrinología Veterinaria y Fisiología de la Reproducción. Zaragoza: Fareso, 1994. JACOBSON, N. L.; MCGILLIARD, A. D. The mammary gland and lactation. Duke’s Physiology of Domestic Animals. 10th edition. Comstock Publishing Associates, Cornell University Press, Ithaca, New York, USA, p. 863-880, 1984. JAINUDEEN, M. R.; HAFEZ, E. S. E. Gestação, fisiologia pré-natal e parto. Revista Brasileira de Reprodução animal, v. 7, p. 141-142, 2004. LIGGINS, G. C. et al. physiological roles of progesterone, oestradiol-17beta and prostaglandin F2alpha in the control of ovine parturition. J Reprod and Fert Suppl, 1972. PÉREZ PÉREZ, F.; PÉREZ GUTIÉRREZ, F. Reproducción animal, inseminación animal y transplante de embriones. Barcelona: Cientifico-medica, 1985. ROBERTS, Stephen J. Obstetricia veterinaria y patología de la reproducción. Montevidéu: Hemiferio Sur, 1979. SALISBURY, G. W.; VANDERMARK, N. L. Phisiology of the reproduction and artificial insemination of cattle. San Francisco : Freeman e Company, 1961, 630 p. SHILLE, V. M. Fisiologia reprodutiva e endocrinologia da fêmea e do macho. Tratado de medicina interna veterinária. São Paulo: Manole, p. 1857-68, 1992. RUTTER, Bruno; RUSSO, Angel F. Fundamentos de la fisiología de la gestación y el parto de los animales domésticos. Buenos Aires: Eudeba, 2002. UNGERFELD, Rodolfo. Reproducción en los animales domésticos. Montevidéu: Melibea, 2002. (shrink)

TRANSPORTE DE GAMETAS, FERTILIZAÇÃO E SEGMENTAÇÃO -/- • _____OBJETIVO -/- O entendimento do desenvolvimento embrionário nos estágios iniciais, desde a deposição dos espermatozoides na fêmea, passando pela fertilização deste no ovócito e na formação do zigoto, é de suma importância para diferenciar especialistas em reprodução e manejo reprodutivo no mercado de trabalho e, também, durante a vida acadêmica. Compreender os processos que levam à formação do zigoto na fêmea é essencial para avaliar a capacidade reprodutiva dos animais e, mediante técnicas, (...) avaliar o trato reprodutivo da fêmea e o desenvolvimento do embrião até a formação do feto e, por fim, em um novo animal sadio na propriedade. Com esse trabalho, o estudante de veterinária ou zootecnia, que deseja se aprofundar na fisiologia da reprodução animal, identificará os mecanismos que são envolvidos no transporte dos gametas, bem como os processos que estes últimos devem completar para alcançar a fertilização e para desencadear as divisões iniciais do embrião. -/- • _____INTRODUÇÃO -/- A fertilização ou fecundação é o processo pelo qual os gametas masculino (espermatozoide) e feminino (ovócito) se fundem para gerar um novo indivíduo. Seu êxito depende da culminação adequada dos diferentes processos que devem sofrer os gametas durante sua maduração e percurso; do transporte oportuno destes no trato reprodutivo da fêmea, assim como de uma série de adaptações dos órgãos genitais internos da mãe. A segmentação refere-se às primeiras divisões celulares do embrião. -/- • _____TRANSPORTE DO OVÓCITO -/- O ovócito que é liberado na ovulação, e que se encontra coberto pelas células do cumulus (figura 1), é capturado pela fímbria do infundíbulo ao aderir aos cílios. Esse processo é altamente eficaz, inclusive em espécies onde os ovários possuem várias formações globosas, por exemplo nas porcas, onde os ovidutos capturam entre 95 e 100% dos ovócitos que são ovulados. As contrações das camadas musculares do oviduto e o movimento intenso dos cílios da mucosa faz com que as secreções fluam em direção ao útero, transportando assim o complexo cumulus-ovócito. Esse transporte é relativamente rápido até alcançar a junção da ampola com o istmo (que é considerado o local de fertilização do espermatozoide e ovócito) a partir do qual se torna lento. Devido a fêmea estar em estro, o processo está sob controle endócrino, isto é, controle hormonal através do estradiol. Nas fêmeas domésticas, ao contrário das mulheres, o transporte ao longo do oviduto é extremamente eficiente, pois os embriões passam para o útero sem dificuldade, de modo que gestações ectópicas (tubárias ou em cavidade) são quase inexistentes. A égua, frequentemente, retém por muito tempo os ovócitos não fertilizados no oviduto, provavelmente devido a não secreção de substâncias (como a prostaglandina E) que poderiam favorecer sua passagem, como se propõe que aconteça com os embriões. A figura 2 apresenta um ovócito com suas respectivas estruturas. Figura 1: ovócitos de uma vaca madurados in vitro. Nota-se as células do cumulus que os recobre. -/- Figura 2: estruturas do ovócito de uma ovelha que se encontra na etapa de ovócito secundário, depois da ovulação. Elaborado pelo autor. • _____TRANSPORTE ESPERMÁTICO -/- Para que os espermatozoides sejam capazes de fertilizar o ovócito, deverão sofrer uma série de mudanças bioquímicas e morfológicas ao longo de sua passagem pelo aparelho reprodutor tanto masculino como feminino. Uma vez produzidos na parede do túbulo seminífero, os espermatozoides são liberados em direção ao lúmen tubular e transportados passivamente para uma estrutura ramificada conhecida como rede testicular (rete testis). Dessa rede são conduzidos em direção ao epidídimo passando através de 10 a 20 ductos eferentes localizados no polo superior do testículo. O epidídimo é dividido em três seções denominadas cabeça, corpo e cauda; é constituído por um só ducto longo e tortuoso que continua com o canal deferente. Ao final desemboca nas ampolas seminais, no ducto ejaculatório e na uretra. As funções do epidídimo são as de maduração, transporte e armazenamento dos espermatozoides. O transporte através do epidídimo é lento, aproximadamente de 10 dias em touros, e segue sendo passivo. Os espermatozoides tomados da cabeça do epidídimo são ainda imaturos e incapazes de fertilizar, enquanto os armazenados na cauda são completamente maduros. Durante o trânsito pelo epidídimo os espermatozoides adquirem motilidade e o potencial para fertilizar, o acrossomo é remodelado e a gota citoplasmática migra para o flagelo e é liberada. Quando um macho ejacula com muita frequência, é possível observar espermatozoides com gota citoplasmática no sêmen, já que não há tempo suficiente para que completem sua maduração. Os espermatozoides são expulsados fora do organismo durante a cópula, na masturbação ou em emissões espontâneas. Na ejaculação, os espermatozoides que se encontram suspensos nos fluidos do testículo e do epidídimo, misturam-se ao chegar na uretra com as secreções das glândulas acessórias para formar o sêmen. Essas secreções denominadas plasma seminal, proporcionam substâncias para manter o metabolismo energético das células espermáticas, e integram suas membranas elementos que impedem uma capacitação prematura. Durante a cópula, o sêmen é depositado na vagina ou no útero, variando entre as espécies (tabela 1). Na monta natural, geralmente, o serviço ocorre no momento propício, já que está definido pela fase do ciclo estral em que a fêmea é receptiva ao macho. No entanto, na inseminação artificial, é o macho que deverá determinar o momento ideal, e para isso é importante considerar a vida média dos gametas, ao qual é muito curta no caso dos ovócitos (tabela 1). -/- Tabela 1: local de depósito do sêmen, volume da ejaculação e vida média dos gametas. Espécie Local de deposição Volume (ml) Velocidade de ejaculação Vida média do ovócito Vida média do espermatozoide Bovinos Intravaginal 2 1 – 3 seg 8 h 30 – 48 h Caninos Intravaginal 2 – 30 (10 média) 6 – 45 min 48 – 72 h 9 – 11 d Equinos Intrauterina 50 – 200 20 – 60 seg 6 – 8 h 72 – 120 h Humanos Intravaginal 3 - - 5 – 6 d Ovinos Intravaginal 1 1 – 2 seg 16 – 24 h 30 – 48 h Suínos Intrauterina 200 – 400 5 – 20 min 8 – 10 h 24 – 48 h Onde d = dias; h = horas. A vida fértil do ovócito é muito curta, portanto, o momento do serviço é de grande importância para obter altos índices de fertilização. -/- Independentemente do local em que os espermatozoides sejam depositados no aparelho reprodutor feminino, serão expostos às secreções genitais e sofrem uma série de mudanças em seu trajeto até o local de fertilização antes de penetrar no ovócito. Nas espécies em que o sêmen é depositado na parte cranial da vagina, uma parte do mesmo penetra através da cérvix, enquanto outra parte é eliminada do aparelho genital da fêmea, em pouco tempo, através do fluxo retrógrado. O meio vaginal não é adequado e imobiliza os espermatozoides em pouco tempo, pelo qual deverão entrar no útero onde o ambiente é mais propício. O transporte espermático na fêmea é o resultado da alta contratilidade, do movimento ciliar e o fluido do aparelho genital durante o estro, ao qual está sob controle endócrino e do sistema nervoso. Esse transporte é favorecido pelas características especiais do muco estral, cujas moléculas formam uma espécie de canais que facilitam a passagem dos espermatozoides. Pelo contrário, durante a fase lútea seu transporte é dificultado. Além do meio vaginal, a cérvix também atua como barreira natural para limitar a passagem dos espermatozoides, diminuindo assim a possibilidade de polispermia. Funciona, também, como um filtro que seleciona os espermatozoides aptos dos que não o são, uma vez que somente os primeiros possuem uma motilidade vigorosa que lhes permite passar pelo muco altamente hidratado. Na vaca a cérvix é considerada como um reservatório espermático. Quando atravessam a cérvix, os espermatozoides seguem sua deslocação tanto por movimento próprio como pelas contrações uterinas e tubárias. Nas espécies em que o local de depósito do sêmen do macho na fêmea é intrauterino, como equinos, a principal barreira que os espermatozoides enfrentam é a união ou junção útero-tubárica. A união entre o útero e o oviduto (istmo do oviduto) serve como reservatório funcional dos espermatozoides nas espécies domésticas. Poucos minutos depois da cópula, é possível encontrar alguns espermatozoides no oviduto, que é conhecido como fase de transporte rápido. No entanto, esses espermato-zoides não são os que participam do processo de fertilização e podem apresentar certas anormalidades. Existe um segundo tipo de transporte denominado fase sustentada, a qual consiste na migração prolongada dos espermatozoides em direção as partes mais craniais do aparelho genital feminino, que conduzem à colonização do reservatório funcional e na liberação gradual dos espermatozoides dos reservatórios espermáticos, incluindo este último. O reservatório do istmo fornece aos espermatozoides um ambiente propício, protegendo-os contra a fagocitose, prolongando assim a sua viabilidade. Aqui os esper-matozoides permanecem aderidos a superfície das células ciliadas do epitélio até a finalização de sua capacitação, depois da qual são liberados quando alteram seu padrão de motilidade flagelada, fenômeno conhecido como hipermotilidade, e migram em ondas em direção ao local da fertilização. Dos milhões de espermatozoides ejaculados, somente alguns milhares alcançarão o istmo do oviduto e um número sumamente pequeno será encontrado nas imediações do ovócito no momento da fertilização. -/- • _____CAPACITAÇÃO ESPERMÁTICA E REAÇÃO ACROSSÔMICA -/- A capacitação é um processo gradual e essencial para a fertilização. Os espermato-zoides devem passar por um dado tempo de “incubação” no aparelho genital da fêmea e sofrer uma série de mudanças antes de serem capazes de fecundar o ovócito. A capacita-ção dos espermatozoides começa quando eles entram em contato com as secreções do aparelho genital da fêmea e termina no istmo do oviduto. Durante esse percurso a superfície da cabeça do espermatozoide se modifica já que algumas moléculas como o colesterol são removidas da membrana plasmática, aumentando sua fluidez e alterando suas propriedades bioquímicas. Entre outras coisas, essa reorganização dos lipídios facilita a entrada de cálcio extracelular pelos canais iônicos e ocasiona a desestabilização da membrana, tornando-a mais fusogênica. Também são eliminados outros fatores (conhecidos genericamente como fatores descapacitantes) que expõem receptores membranais indispensáveis para a realização da união entre o espermatozoide e o ovócito durante a fertilização. Os espermatozoides capacitados apresentam um padrão de hipermotilidade e uma maior atividade metabólica, características que devem obter para que sejam capazes de penetrar as camadas do ovócito. A capacitação é necessária para que ocorra a reação acrossômica. A reação acrossomal ou acrossômica (RA) é um fenômeno de exocitose que é desencadeada pela ligação entre as proteínas e receptores localizados na membrana do espermatozoide e a zona pelúcida do ovócito (figura 3). Envolve a fusão da membrana plasmática do espermatozoide com a membrana externa de seu acrossomo; formando, assim, pequenas vesículas, cujo conteúdo de enzimas hidrolíticas, como a hialuronidase e a acrosina, é liberado em direção ao seu exterior, facilitando a penetração da zona pelúcida. A adesão do espermatozoide à zona pelúcida é específica da espécie e depende de glicoproteínas presentes na membrana dos ovócitos maduros; a cabeça do espermatozoide se une com essas glicoproteínas mediante receptores específicos e atravessam em direção oblíqua a zona pelúcida até chegar ao espaço perivitelino. Nos mamíferos, particularmente em roedores e nos humanos, algumas dessas glicoproteínas são conhecidas como ZP1, ZP2 e ZP3. Pensa-se que a união da membrana espermática a esta última é o que desencadeia a reação acrossomal. Posteriormente, as vilosidades do ovócito entram em contato com o espermatozoide e a membrana presente na secreção equatorial da cabeça do espermatozoide, que tem proteínas fusogênicas específicas, une-se a membrana plasmática do ovócito, fusionando-se e permitindo a entrada do núcleo espermático ao citoplasma (figura 4). A capacitação dos espermatozoides é fundamental para o êxito da fertilização, uma vez que apenas os aptos estarão perfeitos e íntegros para que a união e percepção das glicoproteínas presentes nos mesmos possam ocorrer de forma ideal para a penetração deste no ovócito, fertilizá-lo e formar um zigoto. Figura 3: estrutura do espermatozoide. Nota: a membrana é acrossomal e não acrossonal. Elaborado pelo autor. -/- Figura 4: eventos que ocorrem durante a fertilização. A – depois de passar através das células do cumulus, o espermatozoide entra em contato com a zona pelúcida, onde receptores da membrana plasmática reconhecem as proteínas da zona pelúcida; B – é desencadeada, então, a reação acrossomal; C – para que o espermatozoide penetre na zona pelúcida; D – ao atravessar a zona pelúcida e entrar no espaço perivitelino, a cabeça do espermatozoide entra em contato com a membrana vitelina; ambas membranas se fusionam graças ao reconhecimento de proteínas fusogênicas que estão no segmento equatorial. E – ocorre, então, que o núcleo do espermatozoide penetra no citoplasma do ovócito; uma das consequências da fusão da membrana com a cabeça do espermatozoide é a reação cortical, em que os grânulos corticais do ovócito liberam seu conteúdo em direção ao espaço perivitelino, o que resulta na alteração da estrutura da zona pelúcida e da membrana vitelina para bloquear a polispermia. Elaborado pelo autor. • _____CONSEQUÊNCIAS DA PENETRAÇÃO -/- Bloqueio da polispermia -/- A fusão das membranas dos gametas durante a penetração permite a entrada da fosfolipase C zeta (PLCζ) – fator solúvel que provém do espermatozoide – que desencadeia liberação e oscilações de Ca2+ no retículo endoplasmático. Isso, por sua vez, provoca a migração e fusão dos grânulos corticais, com a consequente liberação de enzimas, que mudam tanto a estrutura da zona pelúcida (por exemplo a inativação de ZP3), como a da membrana vitelina. Desse modo, impede-se que outros espermatozoides as penetrem, evitando assim a polispermia (figura 5). -/- Figura 5: os grânulos corticais que encontram-se na periferia do citoplasma, debaixo da superfície da membrana do ovócito, migram e fusionam-se sobre a mesma, liberando seu conteúdo no espaço perivitelino imediatamente depois da penetração do espermatozoide. A – como conse-quência, tanto a membrana vitelina como a zona pelúcida são modificadas, impedindo a entrada de mais espermatozoides, o que evita a polispermia. B – o ovócito retoma, então, sua segunda divisão meiótica, que ocasiona a expulsão do segundo corpúsculo polar, e na formação dos pronúcleos feminino e masculino. C – continuando, os pronúcleos migram, suas membranas se dissolvem e os cromossomos de ambos se condensam e se unem. Completa-se, assim, a singamia e forma-se, então, o zigoto. Elaborado pelo autor baseado nos livros de embriologia e fisiologia da reprodução conforme vida bibliografia. -/- Ativação do ovócito e formação de pronúcleos -/- Na maioria das fêmeas domésticas, com exceção da cadela, o ovócito encontra-se suspenso na metáfase II da segunda meiose no momento da ovulação. A entrada da PLCζ do espermatozoide no citoplasma do ovócito, e a consequente liberação de Ca2+, faz com que o ovócito se ative, terminando a segunda divisão meiótica e expulse o segundo corpo polar. Posteriormente, o material nuclear do ovócito se reorganiza para formar o pronú-cleo feminino. Entretanto, a membrana nuclear do espermatozoide se dissolve, a cromatina descondensa-se, as protaminas são substituídas por histonas, e se forma uma nova membrana nuclear, dando lugar ao pronúcleo masculino. -/- Singamia -/- Uma vez que os pronúcleos feminino e masculino são formados, migram para o centro do ovócito, aproximam-se, suas membranas se dispersam e os cromossomos paternos e maternos se associam, com o qual recupera a condição diploide e dá origem ao zigoto (figura 5). -/- • _____DESENVOLVIMENTO EMBRIONÁRIO -/- Poucas horas após a fertilização ocorre a primeira divisão do zigoto em duas, depois em 4, 8, 16 e 32 células, denominadas blastômeros. Essas divisões mitóticas são conhecidas como divisões de segmentação ou clivagem (figura 6), uma vez que são realizadas sem aumento do citoplasma, de modo que com cada divisão os blastômeros se tornam menores. A partir das 16 células o embrião se chama mórula, e é visto como uma massa celular compacta. A compactação deve-se a informação de proteínas de ligação entre os blastômeros. O embrião acumula líquido em seu interior, formando uma cavidade denominada blastocele. Esse processo é conhecido como blastulação; o embrião, assim, passa a ser chamado de blastocisto. Nessa etapa é possível diferenciar duas populações de células embrionárias: a massa celular interna, embrioblasto ou botão embrionário (que dará origem ao embrião), e a massa celular externa, células superficiais ou trofoblasto, do qual se originam a maioria das membranas fetais. Ao continuar a multiplicação das células e a acumulação de líquido, o blastocisto aumenta de tamanho, convertendo-se em blastocisto expandido. A zona pelúcida torna-se mais fina e, finalmente, o embrião eclode; isto é, o embrião é liberado da zona pelúcida. -/- • _____FERTILIZAÇÕES ATÍPICAS -/- Polispermia -/- É a penetração de dois ou mais espermatozoides no óvulo. Esta condição é letal nos mamíferos, já que o número cromossômico desse zigoto é maior que 2n, o envelheci-mento do ovócito da porca, como consequência do serviço tardio, favorece a apresentação da polispermia, por isso, é comum ver números de nascimentos de média de 10 a 12 leitões por parição nessa espécie. Nas aves, no entanto, a penetração de mais de um espermatozoide é normal, embora apenas um pronúcleo masculino se formará, fundindo-se com o feminino. -/- Figura 6: etapas do processo de segmentação/clivagem. Fonte: aula de reprodução da professora Domenica Palomaris, UFT. -/- Ginogênese -/- É o desenvolvimento de um embrião a partir de um óvulo normal fecundado por um espermatozoide, mas sem a fusão dos cromossomos masculinos com os da fêmea. A função do espermatozoide, nesse caso, é a de ativação do ovócito para que este inicie seu desenvolvimento, mas não há fusão com o núcleo do espermatozoide. Ocorre em plantas, em nematódeos e em algumas espécies de peixes, por exemplo a Poecilia formosa, espécie em que os ovócitos das fêmeas são ativados por machos de outra espécie relacio-nada. -/- Partenogênese -/- Consiste no desenvolvimento do embrião sem a participação do espermatozoide. Ocorre em alguns insetos, o zangão, por exemplo, é partenogenético. Também pode apresentar-se em perus, cujos embriões são machos e, geralmente, morrem antes da eclosão. -/- • _____GÊMEOS -/- Existem dois tipos de gêmeos: idênticos ou monozigóticos e os não idênticos ou dizigóticos. -/- Idênticos ou monozigóticos -/- Originam-se do mesmo zigoto, sendo assim, possuem o mesmo genótipo e um fenótipo similar e, portanto, são do mesmo sexo. Em laboratório é possível gerá-los ao seccionar uma mórula em duas ou mais partes, por meio de um micromanipulador. Uma vez que possuem o mesmo genótipo, os produtos resultantes são clones. -/- Não idênticos ou dizigóticos -/- Provêm da fertilização de dois óvulos distintos por espermatozoides diferentes. Possuem, portanto, genótipos e fenótipos diferentes, e podem ser de sexo diferente. -/- REFERÊNCIAS BIBLIOGRÁFICAS -/- ALBERTS, Bruce et al. Biologia molecular da célula. Artmed Editora, 2010. AUSTIN, Colin Russell; SHORT, Roger Valentine. Reproduction in Mammals, Book I: Germ Cells and Fertilization. 1982. BEARDEN, Henry Joe et al. Reproducción animal aplicada. México: Manual Moderno, 1982. BOSCH, P.; WRIGHT JR, R. W. The oviductal sperm reservoir in domestic mammals. Archivos de medicina veterinaria, v. 37, n. 2, p. 95-105, 2005. CAPALLEJAS, Roberto Brito; RODRÍGUEZ, Lourdes Tagle. Fisiología de la reproducción animal: con elementos de biotecnología. Editorial Félix Varela, 2010. CROXATTO, Horacio B. Physiology of gamete and embryo transport through the fallopian tube. Reproductive biomedicine online, v. 4, n. 2, p. 160-169, 2002. CUPPS, Perry T. (Ed.). Reproduction in domestic animals. Elsevier, 1991. DIEDRICH, Smidt et al. Endocrinología y Fisiología de la Reproducción de los Animales Zootécnicos. 1972. DUKES, Henry Hugh; SWENSON, Melvin J.; REECE, William O. Dukes fisiologia dos animais domésticos. Editora Guanabara Koogan, 1996. FERREIRA, A. de M. Reprodução da fêmea bovina: fisiologia aplicada e problemas mais comuns (causas e tratamentos). Juiz de Fora: Minas Gerais–Brasil, p. 422, 2010. HAFEZ, Elsayed Saad Eldin; HAFEZ, Bahaa. Reprodução animal. São Paulo: Manole, 2004. HUNTER, Ronald Henry Fraser. The Fallopian tubes in domestic mammals: how vital is their physiological activity?. Reproduction Nutrition Development, v. 45, n. 3, p. 281-290, 2005. HUNTER, R. H. F.; RODRIGUEZ‐MARTINEZ, H. Capacitation of mammalian spermatozoa in vivo, with a specific focus on events in the Fallopian tubes. Molecular Reproduction and Development: Incorporating Gamete Research, v. 67, n. 2, p. 243-250, 2004. GALINA, Carlos; VALENCIA, Javier. Reproducción de los animales domésticos. 2006. HOPPER, Richard M. (Ed.). Bovine reproduction. John Wiley & Sons, 2014. HYTTEL, Poul; SINOWATZ, Fred; VEJLSTED, Morten. Embriologia veterinária. Elsevier Brasil, 2012. KÖLLE, Sabine; REESE, Sven; KUMMER, Wolfgang. New aspects of gamete transport, fertilization, and embryonic development in the oviduct gained by means of live cell imaging. Theriogenology, v. 73, n. 6, p. 786-795, 2010. MCKINNON, Angus O. et al. (Ed.). Equine reproduction. John Wiley & Sons, 2011. OLIVERA, Martha et al. El espermatozoide, desde la eyaculación hasta la fertilización. Revista Colombiana de Ciencias Pecuarias, v. 19, n. 4, p. 426-436, 2006. PLANT, Tony M.; ZELEZNIK, Anthony J. (Ed.). Knobil and Neill's physiology of reproduction. New York: Academic Press, 2014. RODRIGUEZ-MARTINEZ, Heriberto. Role of the oviduct in sperm capacitation. Theriogenology, v. 68, p. S138-S146, 2007. SAAVEDRA LEOS, María Dolores. Estudio de la composición de los gránulos corticales y del oolema de ovocitos porcinos y bovinos madurados y fecundados in vitro. Proyecto de investigación:, 2010. SENGER, Phillip L. et al. Pathways to pregnancy and parturition. Current Conceptions, Inc, 2004. SUAREZ, Susan S. The oviductal sperm reservoir in mammals: mechanisms of formation. Biology of Reproduction, v. 58, n. 5, p. 1105-1107, 1998. VALENCIA MÉNDEZ, Javier de J. Fisiología de la reproducción porcina. 1986. -/- FIXAÇÃO DO ASSUNTO -/- 1. Defina e diferencie fertilização e segmentação. -/- 2. Disserte sobre o transporte do ovócito. Por que no istmo o transporte do ovócito se torna lento? -/- 3. Fale sobre a eficiência do transporte do gameta no trato genital da fêmea e sobre a retenção de ovócitos pela égua. -/- 4. Defina as células do cumulus e explique seu papel sobre o ovócito. -/- 5. Quais as estruturas que compõem o ovócito? Qual a função de cada uma? -/- 6. Todos os ovócitos das fêmeas domésticas são iguais? Justifique. -/- 7. Disserte sobre o papel dos hormônios e das secreções sobre o transporte do ovócito no trato genital da fêmea. -/- 8. Disserte sobre o transporte do espermatozoide. Por que há transporte rápido e lento dos espermatozoides? -/- 9. Fale sobre o local de deposição do sêmen nas espécies domésticas e como esse influen-cia na eficiência da reprodução. -/- 10. Por que a vida média do espermatozoide canino é maior que as outras espécies? -/- 11. Quais as mudanças que os espermatozoides precisam sofrer para conseguir êxito na fertilização e por quê? -/- 12. Defina fase de transporte rápido, fase sustentada e hipermotilidade. Qual a importân-cia de cada um? -/- 13. Como ocorre a reação acrossômica? -/- 14. O que é polispermia e como ocorre seu bloqueio? 15. Como ocorre a ativação do ovócito e como se formam os pronúcleos? -/- 16. O que é e qual a importância da singamia? -/- 17. Disserte sobre as divisões de segmentação e qual a importância destas para o êxito da reprodução. -/- 18. Defina e diferencia mórula e blastocisto. -/- 19. Defina e diferencie ginogênese e partenogênese. -/- 20. Qual o papel endócrino e quais hormônios e enzimas atuam sobre o transporte de gametas, sobre a fertilização e sobre a segmentação? (shrink)

The paper points out that the modern formulation of Bohm’s quantum theory known as Bohmian mechanics is committed only to particles’ positions and a law of motion. We explain how this view can avoid the open questions that the traditional view faces according to which Bohm’s theory is committed to a wave-function that is a physical entity over and above the particles, although it is defined on configuration space instead of three-dimensional space. We then enquire into the status of the (...) law of motion, elaborating on how the main philosophical options to ground a law of motion, namely Humeanism and dispositionalism, can be applied to Bohmian mechanics. In conclusion, we sketch out how these options apply to primitive ontology approaches to quantum mechanics in general. (shrink)

As philosophical and scientific arguments for free will skepticism continue to gain traction, we are likely to see a fundamental shift in the way people think about free will and moral responsibility. Such shifts raise important practical and existential concerns: What if we came to disbelieve in free will? What would this mean for our interpersonal relationships, society, morality, meaning, and the law? What would it do to our standing as human beings? Would it cause nihilism and despair as some (...) maintain or would it rather have a humanizing effect on our practices and policies, freeing us from the negative effects of belief in free will? In this chapter we consider the practical implications of free will skepticism and argue that life without free will and basic desert moral responsibility would not be as destructive as many people believe. We argue that prospects of finding meaning in life or of sustaining good interpersonal relationships, for example, would not be threatened. On treatment of criminals, we argue that although retributivism and severe punishment, such as the death penalty, would be ruled out, preventive detention and rehabilitation programs would still be justified. While we will touch on all these issues below, our focus will be primarily on this last issue. -/- We begin in section I by considering two different routes to free will skepticism. The first denies the causal efficacy of the types of willing required for free will and receives its contemporary impetus from pioneering work in neuroscience by Benjamin Libet, Daniel Wegner, and John-Dylan Haynes. The second, which is more common in the philosophical literature, does not deny the causal efficacy of the will but instead claims that whether this causal efficacy is deterministic or indeterministic, it does not achieve the level of control to count as free will by the standards of the historical debate. We argue that while there are compelling objections to the first route—e.g., Al Mele (2009), Eddy Nahmias (2002, 2011), and Neil Levy (2005)—the second route to free will skepticism remains intact. In section II we argue that free will skepticism allows for a workable morality, and, rather than negatively impacting our personal relationships and meaning in life, may well improve our well-being and our relationships to others since it would tend to eradicate an often destructive form of moral anger. In section III we argue that free will skepticism allows for adequate ways of responding to criminal behavior—in particular, incapacitation, rehabilitation, and alternation of relevant social conditions—and that these methods are both morally justified and sufficient for good social policy. We present and defend our own preferred model for dealing with dangerous criminals, an incapacitation account built on the right to self-protection analogous to the justification for quarantine (see Pereboom 2001, 2013, 2014a; Caruso 2016a), and we respond to recent objections to it by Michael Corrado and John Lemos. (shrink)

The use of the symbol ∨for disjunction in formal logic is ubiquitous. Where did it come from? The paper details the evolution of the symbol ∨ in its historical and logical context. Some sources say that disjunction in its use as connecting propositions or formulas was introduced by Peano; others suggest that it originated as an abbreviation of the Latin word for “or,” vel. We show that the origin of the symbol ∨ for disjunction can be traced to Whitehead and (...) Russell’s pre-Principia work in formal logic. Because of Principia’s influence, its notation was widely adopted by philosophers working in logic (the logical empiricists in the 1920s and 1930s, especially Carnap and early Quine). Hilbert’s adoption of ∨ in his Grundzüge der theoretischen Logik guaranteed its widespread use by mathematical logicians. The origins of other logical symbols are also discussed. (shrink)

Given the fact that many people use Wikipedia, we should ask: Can we trust it? The empirical evidence suggests that Wikipedia articles are sometimes quite good but that they vary a great deal. As such, it is wrong to ask for a monolithic verdict on Wikipedia. Interacting with Wikipedia involves assessing where it is likely to be reliable and where not. I identify five strategies that we use to assess claims from other sources and argue that, to a greater of (...) lesser degree, Wikipedia frustrates all of them. Interacting responsibly with something like Wikipedia requires new epistemic methods and strategies. (shrink)

Psychiatry has witnessed a new wave of approaches to clinical phenotyping and the study of psychopathology, including the National Institute of Mental Health’s Research Domain Criteria, clinical staging, network approaches, the Hierarchical Taxonomy of Psychopathology, and the general psychopathology factor, as well as a revival of interest in phenomenological psychopathology. The question naturally emerges as to what the relationship between these new approaches is – are they mutually exclusive, competing approaches, or can they be integrated in some way and used (...) to enrich each other? In this opinion piece, we propose a possible integration between clinical staging and phenomenological psychopathology. Domains identified in phenomenological psychopathology, such as selfhood, embodiment, affectivity, etc., can be overlaid on clinical stages in order to enrich and deepen the phenotypes captured in clinical staging (‘high resolution’ clinical phenotypes). This approach may be useful both ideographically and nomothetically, in that it could complement diagnosis, enrich clinical formulation, and inform treatment of individual patients, as well as help guide aetiological, prediction, and treatment research. The overlaying of phenomenological domains on clinical stages may require that these domains are reformulated in dimensional rather than categorial terms. This integrative project requires assessment tools, some of which are already available, that are sensitive and thorough enough to pick up on the range of relevant psychopathology. The proposed approach offers opportunities for mutual enrichment: clinical staging may be enriched by introducing greater depth to phenotypes; phenomenological psychopathology may be enriched by introducing stages of severity and disorder progression to phenomenological analysis. (shrink)

The evolution of the human mind through natural selection mandates that our conscious experiences are causally potent in order to leave a tangible impact upon the surrounding physical world. Any attempt to construct a functional theory of the conscious mind within the framework of classical physics, however, inevitably leads to causally impotent conscious experiences in direct contradiction to evolution theory. Here, we derive several rigorous theorems that identify the origin of the latter impasse in the mathematical properties of ordinary differential (...) equations employed in combination with the alleged functional production of the mind by the brain. Then, we demonstrate that a mind--brain theory consistent with causally potent conscious experiences is provided by modern quantum physics, in which the unobservable conscious mind is reductively identified with the quantum state of the brain and the observable brain is constructed by the physical measurement of quantum brain observables. The resulting quantum stochastic dynamics obtained from sequential quantum measurements of the brain is governed by stochastic differential equations, which permit genuine free will exercised through sequential conscious choices of future courses of action. Thus, quantum reductionism provides a solid theoretical foundation for the causal potency of consciousness, free will and cultural transmission. (shrink)

In this paper, I want to focus not on the problems that I believe may threaten Kant’s account of the highest good, but instead on those that I believe threaten the majority of the interpretive reconstructions attempted by commentators and thus prevent the emergence of a consensus in the near future. My goal is to set forth exactly four problems to which I believe any successful interpretation or reconstruction of Kant’s account of the highest good will have to provide substantive (...) solutions and, in doing so, either break new theoretical ground or at least provide a more comprehensive methodology for sorting through the texts. (shrink)

The human mind is constituted by inner, subjective, private, first-person conscious experiences that cannot be measured with physical devices or observed from an external, objective, public, third-person perspective. The qualitative, phenomenal nature of conscious experiences also cannot be communicated to others in the form of a message composed of classical bits of information. Because in a classical world everything physical is observable and communicable, it is a daunting task to explain how an empirically unobservable, incommunicable consciousness could have any physical (...) substrates such as neurons composed of biochemical molecules, water, and electrolytes. The challenges encountered by classical physics are exemplified by a number of thought experiments including the inverted qualia argument, the private language argument, the beetle in the box argument and the knowledge argument. These thought experiments, however, do not imply that our consciousness is nonphysical and our introspective conscious testimonies are untrustworthy. The principles of classical physics have been superseded by modern quantum physics, which contains two fundamentally different kinds of physical objects: unobservable quantum state vectors, which define what physically exists, and quantum operators (observables), which define what can physically be observed. Identifying consciousness with the unobservable quantum information contained by quantum physical brain states allows for application of quantum information theorems to resolve possible paradoxes created by the inner privacy of conscious experiences, and explains how the observable brain is constructed by accessible bits of classical information that are bound by Holevo's theorem and extracted from the physically existing quantum brain upon measurement with physical devices. (shrink)

Capacity of conscious agents to perform genuine choices among future alternatives is a prerequisite for moral responsibility. Determinism that pervades classical physics, however, forbids free will, undermines the foundations of ethics, and precludes meaningful quantification of personal biases. To resolve that impasse, we utilize the characteristic indeterminism of quantum physics and derive a quantitative measure for the amount of free will manifested by the brain cortical network. The interaction between the central nervous system and the surrounding environment is shown to (...) perform a quantum measurement upon the neural constituents, which actualize a single measurement outcome selected from the resulting quantum probability distribution. Inherent biases in the quantum propensities for alternative physical outcomes provide varying amounts of free will, which can be quantified with the expected information gain from learning the actual course of action chosen by the nervous system. For example, neuronal electric spikes evoke deterministic synaptic vesicle release in the synapses of sensory or somatomotor pathways, with no free will manifested. In cortical synapses, however, vesicle release is triggered indeterministically with probability of 0.35 per spike. This grants the brain cortex, with its over 100 trillion synapses, an amount of free will exceeding 96 terabytes per second. Although reliable deterministic transmission of sensory or somatomotor information ensures robust adaptation of animals to their physical environment, unpredictability of behavioral responses initiated by decisions made by the brain cortex is evolutionary advantageous for avoiding predators. Thus, free will may have a survival value and could be optimized through natural selection. (shrink)

The brain is composed of electrically excitable neuronal networks regulated by the activity of voltage-gated ion channels. Further portraying the molecular composition of the brain, however, will not reveal anything remotely reminiscent of a feeling, a sensation or a conscious experience. In classical physics, addressing the mind–brain problem is a formidable task because no physical mechanism is able to explain how the brain generates the unobservable, inner psychological world of conscious experiences and how in turn those conscious experiences steer the (...) underlying brain processes toward desired behavior. Yet, this setback does not establish that consciousness is non-physical. Modern quantum physics affirms the interplay between two types of physical entities in Hilbert space: unobservable quantum states, which are vectors describing what exists in the physical world, and quantum observables, which are operators describing what can be observed in quantum measurements. Quantum no-go theorems further provide a framework for studying quantum brain dynamics, which has to be governed by a physically admissible Hamiltonian. Comprising consciousness of unobservable quantum information integrated in quantum brain states explains the origin of the inner privacy of conscious experiences and revisits the dynamic timescale of conscious processes to picosecond conformational transitions of neural biomolecules. The observable brain is then an objective construction created from classical bits of information, which are bound by Holevo’s theorem, and obtained through the measurement of quantum brain observables. Thus, quantum information theory clarifies the distinction between the unobservable mind and the observable brain, and supports a solid physical foundation for consciousness research. (shrink)

Interactive theorem provers might seem particularly impractical in the history of philosophy. Journal articles in this discipline are generally not formalized. Interactive theorem provers involve a learning curve for which the payoffs might seem minimal. In this article I argue that interactive theorem provers have already demonstrated their potential as a useful tool for historians of philosophy; I do this by highlighting examples of work where this has already been done. Further, I argue that interactive theorem provers can continue to (...) be useful tools for historians of philosophy in the future; this claim is defended through a more conceptual analysis of what historians of philosophy do that identifies argument reconstruction as a core activity of such practitioners. It is then shown that interactive theorem provers can assist in this core practice by a description of what interactive theorem provers are and can do. If this is right, then computer verification for historians of philosophy is in the offing. (shrink)

This paper traces the philosophical concept of life prior to Kant and uses this to contextualize his account of aesthetic judgment as a form of life. It argues on this basis that, according to Kant, the form that taste claims for itself, as explicated in its four moments, results in a demand being placed on the transcendental philosopher to admit the idea of an ultimate subjective basis of all cognitive activities in human beings, that is, a shared principle and form (...) of cognititive life htat is uniquely human. (shrink)

There is a long-standing debate in philosophy about whether it is morally permissible to harm one person in order to prevent a greater harm to others and, if not, what is the moral principle underlying the prohibition. Hypothetical moral dilemmas are used in order to probe moral intuitions. Philosophers use them to achieve a reflective equilibrium between intuitions and principles, psychologists to investigate moral decision-making processes. In the dilemmas, the harms that are traded off are almost always deaths. However, the (...) moral principles and psychological processes are supposed to be broader than this, encompassing harms other than death. Further, if the standard pattern of intuitions is preserved in the domain of economic harm, then that would open up the possibility of studying behavior in trolley problems using the tools of experimental economics. We report the results of two studies designed to test whether the standard patterns of intuitions are preserved when the domain and severity of harm are varied. Our findings show that the difference in moral intuitions between bystander and footbridge scenarios is replicated across different domains and levels of physical and non-physical harm, including economic harms. (shrink)

The badness of having conflicting emotions is a familiar theme in academic ethics, clinical psychology, and commercial self-help, where emotional harmony is often put forward as an ideal. Many philosophers give emotional harmony pride of place in their theories of practical reason.1 Here we offer a defense of a particular species of emotional conflict, namely, ambivalence. We articulate an conception of ambivalence, on which ambivalence is unresolved inconsistent desire (§1) and present a case of appropriate ambivalence (§2), before considering two (...) alternative defenses of emotional conflict (§3). We then argue that inconsistent desires can be fitting (§4) and that it can be reasonable not to resolve inconsistent desires (§5), before considering an objection (§6) and concluding the discussion (§7). (shrink)

The study determined the problem-solving performance and skills of prospective elementary teachers (PETs) in the Northern Philippines. Specifically, it defined the PETs’ level of problem-solving performance in number sense, measurement, geometry, algebra, and probability; significant predictors of their problem-solving performance in terms of sex, socio-economic status, parents’ educational attainment, high school graduated from and subject preference; and their problem-solving skills. The PETs’ problem-solving performance was determined by a problem set consisting of word problems with number sense, measurement, geometry, algebra, and (...) probability. A mixed-method research design was employed. Senior PETs purposively served as a sample where they mostly preferred to teach other subjects than mathematics. PETs who preferred math performed satisfactorily, while prospective teachers who opted for other subjects performed unsatisfactorily. The PETs’ unsatisfactory output indicates the need for remediation to advance the mathematical material skills and enrich the problem-solving abilities of these primary schools' potential teachers. Besides, results showed that subject preference strongly affected and predicted the problem-solving success of the PETs. PETs who preferred to teach mathematics performed significantly better than their counterparts; hence, mathematics as a field of specialization in the Bachelor of Elementary Education program may be considered by teacher education institutions. Further, most PETs displayed lack of problem-solving skills; thus, a Problem-Solving course is recommended for them. (shrink)

The Ockhamist claims that our ability to do otherwise is not endangered by God’s foreknowledge because facts about God’s past beliefs regarding future contingents are soft facts about the past—i.e., temporally relational facts that depend in some sense on what happens in the future. But if our freedom, given God’s foreknowledge, requires altering some fact about the past that is clearly a hard fact, then Ockhamism fails even if facts about God’s past beliefs are soft. Recent opponents of Ockhamism, including (...) David Widerker and Peter van Inwagen, have argued along precisely these lines. Their arguments, if successful, would undermine Ockhamism while avoiding the controversy over the alleged softness of facts about God’s past beliefs. But these arguments do not succeed. The past facts they rely on must be clear and uncontroversial examples of hard facts about the past, and these facts must be such that an ability to refrain from the relevant future action implies an ability to alter the relevant hard fact. We demonstrate the flaw in these arguments by showing how they rely on past facts that do not satisfy these criteria. The Ockhamist may have troubles, but this type of argument is not one of them. (shrink)

The natural evolution of consciousness in different animal species mandates that conscious experiences are causally potent in order to confer any advantage in the struggle for survival. Any endeavor to construct a physical theory of consciousness based on emergence within the framework of classical physics, however, leads to causally impotent conscious experiences in direct contradiction to evolutionary theory since epiphenomenal consciousness cannot evolve through natural selection. Here, we review recent theoretical advances in describing sentience and free will as fundamental aspects (...) of reality granted by quantum physical laws. Modern quantum information theory considers quantum states as a physical resource that endows quantum systems with the capacity to perform physical tasks that are classically impossible. Reductive identification of conscious experiences with the quantum information comprised in quantum brain states allows for causally potent consciousness that is capable of performing genuine choices for future courses of physical action. The consequent evolution of brain cortical networks contributes to increased computational power, memory capacity, and cognitive intelligence of the living organisms. (shrink)

This paper explores the evolution of consciousness and subjectivity through a biological framework for understanding the universe. It posits that functional patterns in biological systems mirror cosmic mathematical principles, defining our objective reality. Similar to wave and Fibonacci patterns in different physical phenomena, biological patterns are intrinsic to all things and can be quantified using Dedre Gentner’s approach to analogy. For example, Earth’s ocean currents and the melting and freezing of Antarctica resemble the circulatory system and heart, while the production (...) of music from instruments is analogous to ribosomal protein synthesis. Shelves, tables, and chairs function like cytosol by holding objects in space, and a coffee cup mirrors red blood cell distribution. These analogies reveal a universal order rooted in biology’s functional patterns, essential for shaping the emergence and evolution of life. The paper traces the development of consciousness from its rudimentary cellular states to complex human cognition, highlighting the role of biologically-patterned environments in driving evolutionary changes. Organisms that recognized and organized according to these patterns evolved as “pattern recognition engines” crucial for survival—thus, Life (survival) being the primary measure of consciousness. Humans advanced this capacity, gaining cognitive freedom by insulating themselves from environmental constraints, but faced increased subjectivity complexity. Consciousness, while inherently subjective and necessary for cognitive development, evolves in humans to understand objective reality and its biological nature, so to understand and navigate complexities of subjectivity. Ultimately, the paper asserts consciousness is the ability to recognize and adhere to life-sustaining patterns and principles. Successful adherence deems them worthy of continued existence, while failure leads to demise. Parallels with historical concepts like Atman and Brahman in Hinduism suggest ancient recognition of the correspondence between human and universal patterns. This ancient understanding, coupled with modern scientific evidence, reveals the interconnectedness and intrinsic biological nature of reality. (shrink)

In his 1918 logical atomism lectures, Russell argued that there are no molecular facts. But he posed a problem for anyone wanting to avoid molecular facts: we need truth-makers for generalizations of molecular formulas, but such truth-makers seem to be both unavoidable and to have an abominably molecular character. Call this the problem of generalized molecular formulas. I clarify the problem here by distinguishing two kinds of generalized molecular formula: incompletely generalized molecular formulas and completely generalized molecular formulas. I next (...) argue that, if empty worlds are logically possible, then the model-theoretic and truth-functional considerations that are usually given address the problem posed by the first kind of formula, but not the problem posed by the second kind. I then show that Russell’s commitments in 1918 provide an answer to the problem of completely generalized molecular formulas: some truth-makers will be non-atomic facts that have no constituents. This shows that the neo-logical atomist goal of defending the principle of atomicity—the principle that only atomic facts are truth-makers—is not realizable. (shrink)

This chapter of the Handbook of Utility Theory aims at covering the connections between utility theory and social ethics. The chapter first discusses the philosophical interpretations of utility functions, then explains how social choice theory uses them to represent interpersonal comparisons of welfare in either utilitarian or non-utilitarian representations of social preferences. The chapter also contains an extensive account of John Harsanyi's formal reconstruction of utilitarianism and its developments in the later literature, especially when society faces uncertainty rather than probabilistic (...) risk. (shrink)

In this chapter, I demonstrate the several fundamental and original aspects of Bamgarten's concpetion of metaphyics that have been overlooked or at least insufficiently investigated. Baumgarten departs from his predecessors, and from many of his contemporaries, by regarding metaphysics as a uniquely human science whose essential purpose is to provide the best instruments for knowing and realising perfection in human life, given that we are subject to essential limitations. This instrumental view of metaphysics leads him to develop seveal Leibnizian ideas (...) regarding perfection and the best possible world into highly articulated metaphysical doctrines that are able to serve as universal guiding principles for all other sciences. In the final part of the chapter, I illustrate three ways in which metaphysics plays this role through an examination of the foundations of Baumgarten's own practical philosophy. (shrink)

Initial responses to questionnaires used to assess participants' understanding of informed consent for malaria vaccine trials conducted in the United States and Mali were tallied. Total scores were analyzed by age, sex, literacy (if known), and location. Ninety-two percent (92%) of answers by United States participants and 85% of answers by Malian participants were correct. Questions more likely to be answered incorrectly in Mali related to risk, and to the type of vaccine. For adult participants, independent predictors of higher scores (...) were younger age and female sex in the United States, and male sex in Mali. Scores in the United States were higher than in Mali (P = 0.005). Despite this difference participants at both sites were well informed overall. Although interpretation must be qualified because questionnaires were not intended as research tools and were not standardized among sites, these results do not support concerns about systematic low understanding among research participants in developing versus developed countries. (shrink)

The electric activities of cortical pyramidal neurons are supported by structurally stable, morphologically complex axo-dendritic trees. Anatomical differences between axons and dendrites in regard to their length or caliber reflect the underlying functional specializations, for input or output of neural information, respectively. For a proper assessment of the computational capacity of pyramidal neurons, we have analyzed an extensive dataset of three-dimensional digital reconstructions from the NeuroMorphoOrg database, and quantified basic dendritic or axonal morphometric measures in different regions and layers of (...) the mouse, rat or human cerebral cortex. Physical estimates of the total number and type of ions involved in neuronal electric spiking based on the obtained morphometric data, combined with energetics of neurotransmitter release and signaling fueled by glucose consumed by the active brain, support highly efficient cerebral computation performed at the thermodynamically allowed Landauer limit for implementation of irreversible logical operations. Individual proton tunneling events in voltage-sensing S4 protein alpha-helices of Na+, K+ or Ca2+ ion channels are ideally suited to serve as single Landauer elementary logical operations that are then amplified by selective ionic currents traversing the open channel pores. This miniaturization of computational gating allows the execution of over 1.2 zetta logical operations per second in the human cerebral cortex without combusting the brain by the released heat. (shrink)

Biological order provided by α-helical secondary protein structures is an important resource exploitable by living organisms for increasing the efficiency of energy transport. In particular, self-trapping of amide I energy quanta by the induced phonon deformation of the hydrogen-bonded lattice of peptide groups is capable of generating either pinned or moving solitary waves following the Davydov quasiparticle/soliton model. The effect of applied in-phase Gaussian pulses of amide I energy, however, was found to be strongly dependent on the site of application. (...) Moving solitons were only launched when the amide I energy was applied at one of the α-helix ends, whereas pinned solitons were produced in the α-helix interior. In this paper, we describe a general mechanism that launches moving solitons in the interior of the α-helix through phase-modulated Gaussian pulses of amide I energy. We also compare the predicted soliton velocity based on effective soliton mass and the observed soliton velocity in computer simulations for different parameter values of the isotropy of the exciton-phonon interaction. The presented results demonstrate the capacity for explicit control of soliton velocity in protein α-helices, and further support the plausibility of gradual optimization of quantum dynamics for achieving specialized protein functions through natural selection. (shrink)

The essential biological processes that sustain life are catalyzed by protein nano-engines, which maintain living systems in far-from-equilibrium ordered states. To investigate energetic processes in proteins, we have analyzed the system of generalized Davydov equations that govern the quantum dynamics of multiple amide I exciton quanta propagating along the hydrogen-bonded peptide groups in α-helices. Computational simulations have confirmed the generation of moving Davydov solitons by applied pulses of amide I energy for protein α-helices of varying length. The stability and mobility (...) of these solitons depended on the uniformity of dipole-dipole coupling between amide I oscillators, and the isotropy of the exciton-phonon interaction. Davydov solitons were also able to quantum tunnel through massive barriers, or to quantum interfere at collision sites. The results presented here support a nontrivial role of quantum effects in biological systems that lies beyond the mechanistic support of covalent bonds as binding agents of macromolecular structures. Quantum tunneling and interference of Davydov solitons provide catalytically active macromolecular protein complexes with a physical mechanism allowing highly efficient transport, delivery, and utilization of free energy, besides the evolutionary mandate of biological order that supports the existence of such genuine quantum phenomena, and may indeed demarcate the quantum boundaries of life. (shrink)

In this chapter we will deal with “mechanizing” induction, i.e. with ways in which theoretical computer science approaches inductive generalization. In the field of Machine Learning, algorithms for induction are developed. Depending on the form of the available data, the nature of these algorithms may be very different. Some of them combine geometric and statistical ideas, while others use classical reasoning based on logical formalism. However, we are not so much interested in the algorithms themselves, but more on the philosophical (...) and theoretical foundations they share. Thus in the first of two parts, we will examine different approaches and inductive assumptions in two particular learning settings. While many machine learning algorithms work well on a lot of tasks, the interpretation of the learned hypothesis is often difficult. Thus, while e.g. an algorithm surprisingly is able to determine the gender of the author of a given text with about 80 percent accuracy [Argamon and Shimoni, 2003], for a human it takes some extra effort to understand on the basis of which criteria the algorithm is able to do so. With that respect the advantage of approaches using logic are obvious: If the output hypothesis is a formula of predicate logic, it is easy to interpret. However, if decision trees or algorithms from the area of inductive logic programming are based purely on classical logic, they suffer from the fact that most universal statements do not hold for exceptional cases, and classical logic does not offer any convenient way of representing statements which are meant to hold in the “normal case”. Thus, in the second part we will focus on approaches for Nonmonotonic Reasoning that try to handle this problem. Both Machine Learning and Nonmonotonic Reasoning have been anticipated partially by work in philosophy of science and philosophical logic. At the same time, recent developments in theoretical computer science are expected to trig- ger further progress in philosophical theories of inference, confirmation, theory revision, learning, and the semantic and pragmatics of conditionals. We hope this survey will contribute to this kind of progress by building bridges between computational, logical, and philosophical accounts of induction. (shrink)

When looking at a scene, observers feel that they see its entire structure in great detail and can immediately notice any changes in it. However, when brief blank fields are placed between alternating displays of an original and a modified scene, a striking failure of perception is induced: identification of changes becomes extremely difficult, even when changes are large and made repeatedly. Identification is much faster when a verbal cue is provided, showing that poor visibility is not the cause of (...) this difficulty. Identification is also faster for objects mentioned in brief verbal descriptions of the scene. These results support the idea that observers never form a complete, detailed representation of their surroundings. In addition, results also indicate that attention is required to perceive change, and that in the absence of localized motion signals it is guided on the basis of high-level interest. (shrink)

A number of cognitive and behavioral variables influence the performance in tasks of theory of mind (ToM). Since two of the most important variables, memory and explicit expression, are impaired in schizophrenic patients, the ToM appears inconsistent in these patients. An ideal instrument of ToM should therefore account for deficient memory and impaired ability of these patients to explicitly express intentions. If such an instrument is developed, it should provide information that can be used not only to understand the pathophysiology (...) but also to monitor patients. (shrink)

This paper defends the Principle of Sufficient Reason, taking Baumgarten as its guide. The primary aim is not to vindicate the principle, but rather to explore the kinds of resources Baumgarten originally thought sufficient to justify the PSR against its early opponents. The paper also considers Baumgarten’s possible responses to Kant’s pre-Critical objections to the proof of the PSR. The paper finds that Baumgarten possesses reasonable responses to all these objections. While the paper notes that in the absence of a (...) response to Kant’s Critical discussion of the PSR, this result does not vindicate the principle, it shows how this discussion provides a deeper understanding of what, according to Baumgarten, the PSR really assumes and intends, and prepares the way for a more responsible discussion of Kant’s critical objections to Baumgarten’s supposed proof. (shrink)

Feynman's sum-over-histories formulation of quantum mechanics has been considered a useful calculational tool in which virtual Feynman histories entering into a coherent quantum superposition cannot be individually measured. Here we show that sequential weak values, inferred by consecutive weak measurements of projectors, allow direct experimental probing of individual virtual Feynman histories, thereby revealing the exact nature of quantum interference of coherently superposed histories. Because the total sum of sequential weak values of multitime projection operators for a complete set of orthogonal (...) quantum histories is unity, complete sets of weak values could be interpreted in agreement with the standard quantum mechanical picture. We also elucidate the relationship between sequential weak values of quantum histories with different coarse graining in time and establish the incompatibility of weak values for nonorthogonal quantum histories in history Hilbert space. Bridging theory and experiment, the presented results may enhance our understanding of both weak values and quantum histories. (shrink)

Five aspects of visual change detection are reviewed. The first concerns the concept of change itself, in particular the ways it differs from the related notions of motion and difference. The second involves the various methodological approaches that have been developed to study change detection; it is shown that under a variety of conditions observers are often unable to see large changes directly in their field of view. Next, it is argued that this “change blindness” indicates that focused attention is (...) needed to detect change, and that this can help map out the nature of visual attention. The fourth aspect concerns how these results affect our understanding of visual perception—for example, the implication that a sparse, dynamic representation underlies much of our visual experience. Finally, a brief discussion is presented concerning the limits to our current understanding of change detection. (shrink)

One of the more powerful impressions created by vision is that of a coherent, richly-detailed world where everything is present simultaneously. Indeed, this impression is so compelling that we tend to ascribe these properties not only to the external world, but to our internal representations as well. But results from several recent experiments argue against this latter ascription. For example, changes in images of real-world scenes often go unnoticed when made during a saccade, flicker, blink, or movie cut. This "change (...) blindness" provides strong evidence against the idea that our brains contain a picture-like representation of the scene that is everywhere detailed and coherent. (shrink)

I characterize and argue against the standard interpretation of logical atomism. The argument against this reading is historical: the standard interpretation of logical atomism (1) fails to explain how the view is inspired by nineteenth-century developments in mathematics, (2) fails to explain how logic is central to logical atomism, and (3) fails to explain how logical atomism is a revolutionary and new "scientific philosophy." In short, the standard interpretation is a bad history of logical atomism. A novel interpretation of the (...) view that repairs these difficulties is sketched in the concluding section. (shrink)

Entanglement measures quantify the amount of quantum entanglement that is contained in quantum states. Typically, different entanglement measures do not have to be partially ordered. The presence of a definite partial order between two entanglement measures for all quantum states, however, allows for meaningful conceptualization of sensitivity to entanglement, which will be greater for the entanglement measure that produces the larger numerical values. Here, we have investigated the partial order between the normalized versions of four entanglement measures based on Schmidt (...) decomposition of bipartite pure quantum states, namely, concurrence, tangle, entanglement robustness and Schmidt number. We have shown that among those four measures, the concurrence and the Schmidt number have the highest and the lowest sensitivity to quantum entanglement, respectively. Further, we have demonstrated how these measures could be used to track the dynamics of quantum entanglement in a simple quantum toy model composed of two qutrits. Lastly, we have employed state-dependent entanglement statistics to compute measurable correlations between the outcomes of quantum observables in agreement with the uncertainty principle. The presented results could be helpful in quantum applications that require monitoring of the available quantum resources for sharp identification of temporal points of maximal entanglement or system separability. (shrink)

Protein α-helices provide an ordered biological environment that is conducive to soliton-assisted energy transport. The nonlinear interaction between amide I excitons and phonon deformations induced in the hydrogen-bonded lattice of peptide groups leads to self-trapping of the amide I energy, thereby creating a localized quasiparticle (soliton) that persists at zero temperature. The presence of thermal noise, however, could destabilize the protein soliton and dissipate its energy within a finite lifetime. In this work, we have computationally solved the system of stochastic (...) differential equations that govern the quantum dynamics of protein solitons at physiological temperature, T=310 K, for either a single isolated α-helix spine of hydrogen bonded peptide groups or the full protein α-helix comprised of three parallel α-helix spines. The simulated stochastic dynamics revealed that although the thermal noise is detrimental for the single isolated α-helix spine, the cooperative action of three amide I exciton quanta in the full protein α-helix ensures soliton lifetime of over 30 ps, during which the amide I energy could be transported along the entire extent of an 18-nm-long α-helix. Thus, macromolecular protein complexes, which are built up of protein α-helices could harness soliton-assisted energy transport at physiological temperature. Because the hydrolysis of a single adenosine triphosphate molecule is able to initiate three amide I exciton quanta, it is feasible that multiquantal protein solitons subserve a variety of specialized physiological functions in living systems. (shrink)

I claim that a relatively new position in philosophy of mathematics, pluralism, overlaps in striking ways with the much older Jain doctrine of anekantavada and the associated doctrines of nyayavada and syadvada. I first outline the pluralist position, following this with a sketch of the Jain doctrine of anekantavada. I then note the srrong points of overlaps and the morals of this comparison of pluralism and anekantavada.

The use of artificial intelligence in philosophy opens new avenues for inquiry, particularly through dialogical methods inspired by the Socratic tradition. This paper exemplifies the engagement with ChatGPT-4o by OpenAI as a philosophical interlocutor, highlighting how this format facilitates a clear distinction between the philosopher's contributions and those generated by the AI. By allowing the philosopher to lead the dialogue, this technique liberates him from the constraints of drafting and formal writing, enabling a more spontaneous exploration of ideas. The conversation (...) begins with a foundational definition of intelligence and progresses toward a deeper and philosophically relevant understanding. This exchange not only showcases the potential of AI to enrich philosophical discourse but also emphasizes the significance of critical questioning in examining complex concepts such as intelligence and the implications of artificial cognition. (shrink)

Macromolecular protein complexes catalyze essential physiological processes that sustain life. Various interactions between protein subunits could increase the effective mass of certain peptide groups, thereby compartmentalizing protein α-helices. Here, we study the differential effects of applied massive barriers upon the soliton-assisted energy transport within proteins. We demonstrate that excentric barriers, localized onto a single spine in the protein α-helix, reflect or trap three-spine solitons as effectively as concentric barriers with comparable total mass. Furthermore, wider protein solitons, whose energy is lower, (...) require heavier massive barriers for soliton reflection or trapping. Regulation of energy transport, delivery and utilization at protein active sites could thus be achieved through control of the soliton width, or of the effective mass of the protein subunits. (shrink)

Enactivism has the potential to provide a sense of teleology in purpose-directed action, but without violating the principles of efficient causation. Action can be distinguished from mere reaction by virtue of the fact that some systems are self-organizing. Self-organization in the brain is reflected in neural plasticity, and also in the primacy of motivational processes that initiate the release of neurotransmitters necessary for mental and conscious functions, and which guide selective attention processes. But in order to flesh out the enactivist (...) approach in a way that is plausible and not merely an epiphenomenon, it is necessary to confront the problem of causal closure in a serious way. Atoms and molecules in the brain do not violate the normal causal principles that govern them in other contexts. The theory of self-organizing dynamical systems must be developed in a way that is compatible with causal closure rather than contradicting it. (shrink)

[Ronald de Sousa] Taking literally the concept of emotional truth requires breaking the monopoly on truth of belief-like states. To this end, I look to perceptions for a model of non-propositional states that might be true or false, and to desires for a model of propositional attitudes the norm of which is other than the semantic satisfaction of their propositional object. Those models inspire a conception of generic truth, which can admit of degrees for analogue representations such as emotions; (...) belief-like states, by contrast, are digital representations. I argue that the gravest problem-objectivity-is not insurmountable. /// [Adam Morton ] It is accuracy rather than truth itself that is valuable. Emotional truth is a dubious though attractive notion, but emotional accuracy is much easier to make sense of. My approach to accuracy goes via an account of what makes a story accurate. Stories can be accurate but not true, and emotions can be accurate whether or not they are true. The capacity for emotional accuracy, for emotions that fit a person's situation, is an aspect of emotional intelligence, which is as important an aspect of rational human agency as the intelligent formation of beliefs and desires. (shrink)