An orthodox view in marketing ethics is that it is morally impermissible to market goods to specially vulnerable populations in ways that take advantage of their vulnerabilities. In his signature article “Marketing and the Vulnerable,” Brenkert (Bus Ethics Q Ruffin Ser 1:7–20, 1998) provided the first substantive defense of this position, one which has become a well-established view in marketing ethics. In what follows, we throw new light on marketing to the vulnerable by critically evaluating key components of Brenkert’s general (...) arguments. Specifically, we contend that Brenkert has failed to offer us any persuasive reasons to think that it is immoral to market to the vulnerable in ways that take advantage of their vulnerability. Although Brenkert does highlight the fact that the specially vulnerable are at greater risk of being harmed by already immoral marketing practices (e.g., deception, manipulation), he fails to establish that the specially vulnerable are a unique moral category of market clients or that there are special moral standards that apply to them. Moreover, even if Brenkert’s position were theoretically defensible, the practical implications of his position are far less tenable than he suggests. If our criticisms are sound, then Brenkert and others who endorse his position are seriously mistaken regarding how one can permissibly market products to vulnerable populations, and, in addition, they have improperly categorized certain morally permissible marketing practices as being immoral. (shrink)

Recent research has begun to investigate sensory processing in relation to nonclinical variation in traits associated with the autism spectrum disorders (ASD). We propose that existing accounts of autistic perception can be augmented by considering a role for individual differences in top-down expectations for the precision of sensory input, related to the processing of state-dependent levels of uncertainty. We therefore examined ASD-like traits in relation to the rubber-hand illusion: an experimental paradigm that typically elicits crossmodal integration of visual, tactile, and (...) proprioceptive information in an unusual illusory context. Individuals with higher ASD-like traits showed reduced effects of the rubber-hand illusion on perceived arm position and reach-to-grasp movements, compared to individuals with lower ASD-like traits. These differences occurred despite both groups reporting the typical subjective experience of the illusion concerning visuotactile integration and ownership for the rubber hand. Together these results suggest that the integration of proprioceptive information with cues for arm position derived from the illusory context differs between individuals partly in relation to traits associated with ASD. We suggest that the observed differences in sensory integration can be best explained in terms of differing expectations regarding the precision of sensory estimates in contexts that suggest uncertainty. (shrink)

Exploration of a hypothetical model of the structure of the Emergent Event. -/- Key Words: Emergent Event, Foundational Mathematical Categories, Emergent Meta-system, Orthogonal Centering Dialectic, Hegel, Sartre, Badiou, Derrida, Deleuze, Philosophy of Science.

Ethics, Policy & Environment, Volume 14, Issue 3, Page 345-359, October 2011.

Investigation of neural and cognitive processes underlying individual variation in moral preferences is underway, with notable similarities emerging between moral- and risk-based decision-making. Here we specifically assessed moral distributive justice preferences and non-moral financial gambling preferences in the same individuals, and report an association between these seemingly disparate forms of decision-making. Moreover, we find this association between distributive justice and risky decision-making exists primarily when the latter is assessed with the Iowa Gambling Task. These findings are consistent with neuroimaging studies (...) of brain function during moral and risky decision-making. This research also constitutes the first replication of a novel experimental measure of distributive justice decision-making, for which individual variation in performance was found. Further examination of decision-making processes across different contexts may lead to an improved understanding of the factors affecting moral behaviour. (shrink)

Imre Lakatos' conception of the history of science is explicated with the purpose of replying to criticism leveled against it by Thomas Kuhn, Ian Hacking, and others. Kuhn's primary argument is that the historian's internal—external distinction is methodologically superior to Lakatos' because it is "independent" of an analysis of rationality. That distinction, however, appears to be a normative one, harboring an implicit and unarticulated appeal to rationality, despite Kuhn's claims to the contrary. Lakatos' history, by contrast, is clearly the history (...) of a normatively defined discipline; of science and not scientists and their activities. How such history can be written, the historiographic and critical tools available for its construction, and its importance as history, are considered in detail. In an afterword, the prevalence of Lakatos' treatment of history in philosophical discussion is indicated: A related approach is shown to arise in social contract theory. (shrink)

Common goods and political sovereignty of nation-states are intertwined, since without government the orderly treatment of common goods would be unlikely. But large corporations, especially global multinationals, reshape and restrict national sovereignty through economic forces. Consequently, corporations have specific social responsibilities. This article articulates those responsibilities as they pertain to managing common goods.

The constitutions of many nations have been explicitly or implicitly founded upon principles of the social contract derived from Thomas Hobbes. The Hobbesian egoism at the base of the contract fairly accurately represents the structure of market enterprise. A contractarian analysis may, then, allow for justified or rationally acceptable universal standards to which businesses should conform. This paper proposes general rational restrictions upon multi-national enterprises, and includes a critique of unjustified restrictions recently proposed by the Organization for Economic Cooperation and (...) Development (OECD). I propose restrictions that may be tighter than the OECD and international law currently demand, because reason requires that the activities of enterprises accord with standards of environmental and governmental sustainability in addition to consortium, national law and international law agreements. I argue that it is justifiable that indictments may be presented by a citizen or a government against the local arm of a multinational enterprise in response to violations committed by an arm within a different country. (shrink)

Constructions of the animal and animality are often pivotal to religious discourses. Such constructions create the possibility of identifying and valuing what is "human" as opposed to the "animal" and also of distinguishing human beliefs and behaviors that can be characterized as being animal from those that are "truly human." Some discourses also employ the concept of savagery as a bridge between the human and the animal, where the form of humanity but not its ideal beliefs and practices can be (...) displayed. This paper explores the work of the influential scientist, philosopher, and theologian A. N. Whitehead in this context. His ideas of what constitutes "the animal," the "primitive" and the "civilized" are laid out explicitly in his now little-used history of religions text, Religion in the Making. This paper explores these ideas in this history and then considers how the same ideas permeate his currently more popular philosophical and theological writing Process and Reality. Drawing on some work in post-colonial theory, the paper offers a critique of this understanding of animality, savagery, and civilization and suggests that using Whitehead to underpin modern theological work requires considerable caution. (shrink)

Scholars have associated the character of Pangloss in Voltaire’s Candide variously with the ideas of Gottfried Leibniz, Alexander Pope, and Christian Wolff. With them he is associated, but on whom is he modeled? Pangloss is the image of a French popularizer of science celebrated in his day but little noticed in ours: Noël Antoine Pluche (1688-1761), the author of a highly popular work, Le Spectacle de la Nature.

(Conference proceedings 2014) This presentation (International Development Ethics Association, July 2014) considers economic vulnerability, exploring the risk of deprivation of necessary resources due to a complex and rarely discussed vulnerability that arises from hope. Pierre Bourdieu’s sociological account of French petit-bourgeois aspiration in The Social Structures of the Economy has recently inspired Wendy Olsen to introduce the term “aspiration paradox” to characterize cases wherein “a borrower's status aspirations may contribute to a situation in which their borrowings exceed their capacity to (...) repay,” leaving the individual much the worse, due to an aspiration to betterment. If such financial opportunities were not made available to these people – if some were denied loans due to a careful assessment of their vulnerability – would they be better off? We should seriously consider that they might be. I will hazard the straightforwardly paternalistic suggestion that limiting access to lending to those who are vulnerable to their aspirations can be a just policy. Because aspiration paradox is a cross-cultural phenomenon, and because lending frequently involves asymmetries in mathematical education between borrowers and lenders, I hope to elude at least some of the charges of colonialism that have gained a stronger purchase on adaptive preference arguments. (shrink)

(Article part 2 of 2) This introduction notes the contributions of authors to the second issue of the Journal of Global Ethics 2015 Sustainable Development Goals Forum. It briefly explains the process through which the Sustainable Development Goals have developed from their receipt in 2014 to their passage in September 2015 by the UN General Assembly, and it considers their development in prospect. The Millennium Development Goals, which spanned 1990–2015, present a case study that reveals the changeability of such long-term (...) multilateral commitments. They were enmeshed in overlapping and inconsistent national and intergovernmental commitments reaching from 1995 to 2005, and the text of those goals also evolved, stabilizing for the last time in 2007. The SDGs and attendant commitments should be expected to evolve similarly over their 15-year run. This presents a concern, for among the three committees established by the UN to create the goals, the two committees charged with public consultation were retired as pl.. (shrink)

(Article part 1 of 2) This introduction notes the contributions of various authors to the first issue of the Journal of Global Ethics 2015 Forum and briefly explains the United Nations process through which the sustainable development goals have been formulated up to the receipt by the General Assembly, in August 2014, of the Report of the Open Working Group of the General Assembly on Sustainable Development Goals. The goals are identified as a confluence of distinct streams of UN work (...) attended to variously by policy experts and political figures in the past several decades. Sources include, most obviously, the Millennium Declaration of 2000 and the Millennium Development Goals, but also the 1992 United Nations Conference on Environment and Development, the Human Development Reports of 1990 forward, and the 1987 Brundtland Report. (shrink)

It is frequently claimed that breeding animals that we know will have unavoidable health problems is at least prima facie wrong, because it harms the animals concerned. However, if we take ‘harm’ to mean ‘makes worse off’, this claim appears false. Breeding an animal that will have unavoidable health problems does not make any particular individual animal worse off, since an animal bred without such problems would be a different individual animal. Yet, the intuition that there is something ethically wrong (...) about breeding animals—such as purebred pedigree dogs—in ways that seem negatively to affect welfare remains powerful. In this paper, an animal version of what is sometimes called the non-identity problem is explored, along with a number of possible ways of understanding what might be wrong with such breeding practices, if it is not that they harm the animal itself. These possibilities include harms to others, placeholder arguments, non-comparative ideas of harm, an ‘impersonal’ approach, and concerns about human attitudes and dispositions. (shrink)

Distributive justice decision making tends to require a trade off between different valued outcomes. The present study tracked computer mouse cursor movements in a forced-choice paradigm to examine for tension between different parameters of distributive justice during the decision-making process. Participants chose between set meal distributions, to third parties, that maximised either equality (the evenness of the distribution) or efficiency (the total number of meals distributed). Across different formulations of these dilemmas, responding was consistent with the notion that individuals tend (...) to base decisions in part on the magnitude of these parameters. In addition, dilemmas associated with inconsistent responding across the sample tended to elicit the greatest spatial deviation of the cursor, potentially reflecting dilemma difficulty. One interpretation of these results is that individuals value equality and efficiency in such a way that moral dilemmas are resolved by comparing the perceived value of these qualitatively different parameters, consistent with a value pluralistic framework of decision making. A post-hoc analysis indicated that individuals also incorporated sufficiency concerns during distributive justice decision making. The results are discussed in relation to political philosophy. (shrink)

How coherent is Descartes' conception of vacuum in the Principles? Descartes' arguments attacking the possibility of vacuum are difficult to read and to understand because they reply to several distinct threads of discussion. I separate two strands that have received little careful attention: the scholastic topic of annihilation of space, particularly represented in Albert of Saxony, and the physical arguments concerning vacuum in Galileo that are also continued after the publication of the Principles in Pascal. The distinctness of the two (...) sorts of opponent accounts for Descartes' odd habit of summarily declaring vacuum "contradictory" in some contexts, while providing extended conceptual and physical arguments meant to establish its "impossibility" in others. In several passages late in the Principles, Descartes also considers the physical ramifications of "empty space," including a discussion of the appearance of a star, were an empty space situated at the center of the celestial vortex. I argue that the discussion allows for a sensible conception of space with extension, but without matter, quite adequate to the physical discussions of vacuum among Descartes' contemporaries. (shrink)

This 4000 word entry to Routledge’s Handbook of Development Ethics (Jay Drydyk & Lori Keleher, eds., 2018) considers development within United States of America and Canada. Indigenous peoples and their nations are also featured. Canada and USA are both characterized by the UN Development Program as maintaining very high human development. Addressable weaknesses are nevertheless evident when performance is compared, for example, with OECD member nations. This entry focuses upon such comparison, noting characteristic political institutions and attendant social inequality in (...) the areas of social welfare, education and health. The histories of both nations over the past half-century suggest that cultural shifts within USA have displaced the ethos of social responsibility that the country had previously shared with Canada, replacing it with an ideal of self-reliance. The turn may be a factor in the USA’s increasing inequality and general weakness in social welfare programs since the 1980s. Events since 2016 especially also display a turn towards another ideal of self-reliance: isolationism. USA’s reduction in global commitments – to open trade, to limits on environmental impact, and especially, to immigration – contrast greatly with Canada’s evolving commitment to a global society and to a cultural ideal of multiple non-assimilated cultures within its borders, including cultures of new immigrant populations. Canada is by many measures a more equal society, but it shares with USA continued failings in development for aboriginal groups and vulnerability for that group and others. (shrink)

(Pre-publication draft November 2015: Partial content of "Introduction: The 2030 Agenda," Journal of Global Ethics 11:3 [December 2015], 262-270) This introduction briefly explains the process through which the Sustainable Development Goals have developed from their receipt in 2014 to their passage in September 2015 by the UN General Assembly, and it considers their development in prospect. The Millennium Development Goals, which spanned 1990-2015, present a case study that reveals the changeability of such long-term multilateral commitments. They were enmeshed in overlapping (...) and inconsistent national and intergovernmental commitments reaching from 1995 to 2005, and the text of those goals also evolved, stabilizing for the last time in 2007. The Sustainable Development Goals and attendant commitments should be expected to evolve similarly over their fifteen year run. This presents a concern, for among the three committees established by the UN to create the goals, the two committees charged with public consultation were retired as planned in 2014. The process evident thereafter has displayed a shift towards a strategy of enrolling broad public endorsement that leaves such consultation and specific responsibility to those consulted in doubt. This bodes ill for public deliberation on the goals and for public accountability as the agenda proceeds towards 2030. (shrink)

The Call for Papers for this conference suggests the topic, “international codes of business conduct.” This paper is intended to present a shift from a discussion of codes, or constraints to be placed upon business, to an entirely different topic: to responsibility, which yields duty, and the reciprocal concept, right. Beyond the framework of external regulation and codes of conduct, voluntary or otherwise, lies another possible accounting system: one of real corporate responsibility, which arises out of the evident capability of (...) businesses to engage in rationally self-regulated activity. If such responsibility can be shown to be comprehensible, then it could bind the activities of corporations ethically, and in rationally compelling legitimate law, just as your activities and mine are bound. Perhaps we can bind the officers of corporations as responsible persons, but I would like to introduce an undiminished conception of responsibility that will back legitimate law for the corporations themselves, as artificial persons. That is the purpose of Part 1 of this paper. In Part 2 I will turn to the case of multinational corporations in particular. I will draw conclusions regarding their general duties and rights, and will dip explicitly into ethical formulations, as well as the ground of legitimate law. I will also indicate a particular rational requirement, or duty, for politically and environmentally sustainable business practices of multinationals. In Part 3 I will discuss jurisdiction for instituting legal sanctions in multinational cases. I will argue that the national laws and civil suits that may be pursued within a court in one nation can actually stand as legitimate checks against abuses carried out by the arms of multinational corporations that reside in other nations. (shrink)

This essay develops a thesis regarding the manner through which social institutions such as property come to be, and a second thesis regarding how such institutions ought to be legitimated. The two theses, outlined below, are in need of explication largely because of the entrenched cultural influence of an erroneous reading of social contract theory concerning the historical origins of the state. In part A, I introduce that error. I proceed in parts B and C to present two central theses (...) about institutions: Thesis 1: The construction of social institutions can be understood clearly only if that topic is distinguished from the topic of their normative status, or legitimacy. Thesis 2: The normative status of such institutions can be understood properly only if their legitimacy is distinguished from the legitimacy of government. With the distinction of Thesis 1 in place, an informative socio-technical account of the construction of institutions can be formulated with little ado. This allows for clarity concerning how institutions might be legitimated (Thesis 2), and consequently, legitimation can proceed. Some fundamentals of legitimation from a Kantian perspective are outlined in Part C. (shrink)

Case study for Business Ethics, 5000 words. Considers the state of the payday lending market in USA and Canada as of March 2018. Suitable for undergraduate or business school use. Includes the discussion of: Storefront and online payday lending in state/province and national contexts. Applicability of the concept of exploitation to payday lending. Alternatives to payday lending ("Payday Alternative Loans" provided through credit unions, and savings incentive programs that reduce demand for payday lending). U.S. government regulation of 2017 that was (...) rescinded shortly before it was to have effects on business, specifically due to change of Presidential administration (January 2018). Class discussion questions. References. (shrink)

This chapter examines the relation of the Human Development or Capability Approach to liberal political theory. If development is enhancement of capabilities, then this chapter adds that development is human and social: development includes (1) the creation of value as a social process that is (2) a dialectical product of people in their relations. Specifically: (1) The place of the individual within political theory must be revised if the political subject is, as Carol Gould argues, an “individual-in-relations” rather than an (...) autonomous individual agent. (2) New possibilities for valuation are also relational: value is created dialectically along with those possibilities through processes that may be modeled on Denis Goulet’s account of dialectical recognition. These axiological claims hold importance for the place of democratic participation in just politics and development. Building upon David Crocker’s work, this chapter argues that just politics may require a participative approach that is undercut by Martha Nussbaum’s suggestion that a list of central capabilities should guide the drafting of national constitutions. The assimilation of the indigenous concept sumak kawsay to the ideal of buen vivir within Ecuador’s constitution is illustrative, suggesting that prior specification (a list) may limit and distort the dialectical generation of new capabilities. (shrink)

This chapter explores the idea that the need to establish common knowledge is one feature that makes social cognition stand apart in important ways from cognition in general. We develop this idea on the background of the claim that social cognition is nothing but a type of causal inference. We focus on autism as our test-case, and propose that a specific type of problem with common knowledge processing is implicated in challenges to social cognition in autism spectrum disorder (ASD). This (...) problem has to do with the individual’s assessment of the reliability of messages that are passed between people as common knowledge emerges. The proposal is developed on the background of our own empirical studies and outlines different ways common knowledge might be comprised. We discuss what these issues may tell us about ASD, about the relation between social and non-social cognition, about social objects, and about the dynamics of social networks. (shrink)

I briefly consider why Descartes stopped work on the _Rules_ towards the end of my paper. My main concern is to accurately characterize the project represented in the _Rules_, especially in its relation to early-modern logic.

A new advanced systems theory concerning the emergent nature of the Social, Consciousness, and Life based on Mathematics and Physical Analogies is presented. This meta-theory concerns the distance between the emergent levels of these phenomena and their ultra-efficacious nature. The theory is based on the distinction between Systems and Meta-systems (organized Openscape environments). We first realize that we can understand the difference between the System and the Meta-system in terms of the relationship between a ‘Whole greater than the sum of (...) the parts’ and a ‘Whole less than the sum of its parts’, i.e., a whole full of holes (like a sponge) that provide niches for systems in the environment. Once we understand this distinction and clarify the nature of the unusual organization of the Meta-system, then it is possible to understand that there is a third possibility which is a whole exactly equal to the sum of its parts that is only supervenient like perfect numbers. In fact, there are three kinds of Special System corresponding to the perfect, amicable, and sociable aliquot numbers. These are all equal to the sum of their parts but with different degrees of differing and deferring in what Jacques Derrida calls “differance”. All other numbers are either excessive (systemic) or deficient (metasystemic) in this regard. The Special Systems are based on various mathematical analogies and some physical analogies. But the most important of the mathematical analogies are the hypercomplex algebras, which include the Complex Numbers, Quaternions, and Octonions, with the Sedenions corresponding to the Emergent Meta-system. However, other analogies are the Hopf fibrations between hyperspheres of various dimensions, nonorientable surfaces, soliton solutions, etc. These Special Systems have a long history within the tradition since they can be traced back to the imaginary cities of Plato. The Emergent Meta-system is a higher order global structure that includes the System with the three Special Systems as a cycle. An example of this from our tradition is in the Monadology of Gottfried Wilhelm von Leibniz. There is a conjunctive relationship between the System schema and the Special Systems that produce the Meta-system schema cycle. The Special Systems are a meta-model for the relationship between the emergent levels of Consciousness (Dissipative Ordering based on the theory of negative entropy of Prigogine), Living (Autopoietic Symbiotic based on the theory of Maturana and Varela), and Social (Reflexive based on the theory of John O’Malley and Barry Sandywell). These different special systems are related to the various existenitals identified by Martin Heidegger in Being and Time and various temporal reference frames identified by Richard M. Pico. We also relate the special systems to morphodynamic and teleodynamic systems of Terrence Deacon in Incomplete Nature to which we add sociodynamic systems to complete the series of Special Systems. (shrink)

This chapter presents a historical study of how science has developed and of how philosophical theories of many sorts – philosophy of science, theory of the understanding, and philosophical theology – both enable and constrain certain lines of development in scientific practice. Its topic is change in the legitimacy or acceptability of scientific explanation that invokes purposes, or ends; specifically in the argument from design, in the natural science field of physico-theology, around the start of the eighteenth century. ... The (...) context that produced physico-theology was clearly religious and political. It is unsurprising that a large body of Protestant intellectuals well-placed in a relatively peaceful society with a strong tradition of open speech, would develop links between science and critical discussion of both divinity and the Bible. There were also bounds to the discussion, as Newton, who chose to sit on the sidelines, knew well. Many others on Europe’s continent lived much more intimately with religious division as well as the reminder, in 1633, of Galileo’s failure to arrange a peaceable arrangement between science and religion. These aspects of the rise of physico-theology have not been the focus of this chapter, which has surveyed the philosophical and social origins found in the English context. Science, philosophy of science and other English philosophical currents – most particularly the theory of ideas and understanding that we are familiar with in its later development by John Locke – were formative for a field that might alternatively have been called ‘empirical natural theology.’ Prior shifts in religious sensibility that emptied the Book of Nature of much of its content also prepared the ground. Other philosophical and theological currents not discussed here – most notably theories of divine agency and predestination – and other philosophical trends – the rise of Spinoza’s challenge to such natural theology on the continent – also had both shaping and limiting influences upon the field. Finally, philosophers, including natural philosophers, did much more to promote physico-theology than just write about it: Boyle in particular provided a very important launch pad for the further development of an already healthy tradition of natural theology with his named lectureship, which drew the interest of others in the Royal Society, most notably Isaac Newton, and which spawned two of the most influential physico-theological tracts shortly before and shortly after the turn of the eighteenth century. (shrink)

What did Descartes regard as subject to doubt, and what was beyond doubt, in the Meditations? A review of the Objections and Descartes' reactions in the Replies provides some useful clarification, but viewing Descartes' method of doubt in conjunction with his professed theory of knowledge in the Rules for the Direction of the Mind further elucidates his own understanding of the project. In the Rules, Descartes introduces the mind's intuition of "simple natures" as the atomistic basis of all knowledge, its (...) form as well as its content. The simple natures, Descartes claims, can only be understood thoroughly, and I argue that Descartes' doubt in the  Meditations appears not to include doubt of simple natures. A related attempt to link the earlier work to the Meditations by Peter Schouls is considered and criticized; I suggest as an alternative that there are three classes of objects pertaining to the construction of knowledge in the Meditations: a) first principles and concepts that are constituents of other knowledge, intuited and not doubted, nor called 'knowledge' by Descartes; b) what Descartes calls clearly and distinctly perceived knowledge that survives doubt, known through a kind of intuition; and c) science, as remembered collections of clearly and distinctly perceived knowledge. Finally, because the two works do have important dissimilarities, I also consider how differences between the Rules and the Meditations might affect the applicability of the simple natures to the arguments of the Meditations, especially in the light of clues found in the intellectual autobiography of the Discourse on Method. (shrink)

Explorations in Systems Phenomenology in Relation to Ontology, Hermeneutics and the Meta-dialectics of Design -/- SYNOPSIS A Phenomenological Analysis of Emergent Design is performed based on the foundations of General Schemas Theory. The concept of Sign Engineering is explored in terms of Hermeneutics, Dialectics, and Ontology in order to define Emergent Systems and Metasystems Engineering based on the concept of Meta-dialectics. -/- ABSTRACT Phenomenology, Ontology, Hermeneutics, and Dialectics will dominate our inquiry into the nature of the Emergent Design of the (...) System and its inverse dual, the Meta-system. This is an speculative dissertation that attempts to produce a philosophical, mathematical, and theoretical view of the nature of Systems Engineering Design. Emergent System Design, i.e., the design of yet unheard of and/or hitherto non-existent Systems and Metasystems is the focus. This study is a frontal assault on the hard problem of explaining how Engineering produces new things, rather than a repetition or reordering of concepts that already exist. In this work the philosophies of E. Husserl, A. Gurwitsch, M. Heidegger, J. Derrida, G. Deleuze, A. Badiou, G. Hegel, I. Kant and other Continental Philosophers are brought to bear on different aspects of how new technological systems come into existence through the midwifery of Systems Engineering. Sign Engineering is singled out as the most important aspect of Systems Engineering. We will build on the work of Pieter Wisse and extend his theory of Sign Engineering to define Meta-dialectics in the form of Quadralectics and then Pentalectics. Along the way the various ontological levels of Being are explored in conjunction with the discovery that the Quadralectic is related to the possibility of design primarily at the Third Meta-level of Being, called Hyper Being. Design Process is dependent upon the emergent possibilities that appear in Hyper Being. Hyper Being, termed by Heidegger as Being (Being crossed-out) and termed by Derrida as Differance, also appears as the widest space within the Design Field at the third meta-level of Being and therefore provides the most leverage that is needed to produce emergent effects. Hyper Being is where possibilities appear within our worldview. Possibility is necessary for emergent events to occur. Hyper Being possibilities are extended by Wild Being propensities to allow the embodiment of new things. We discuss how this philosophical background relates to meta-methods such as the Gurevich Abstract State Machine and the Wisse Metapattern methods, as well as real-time architectural design methods as described in the Integral Software Engineering Methodology. One aim of this research is to find the foundation for extending the ISEM methodology to become a general purpose Systems Design Methodology. Our purpose is also to bring these philosophical considerations into the practical realm by examining P. Bourdieu’s ideas on the relationship between theoretical and practical reason and M. de Certeau’s ideas on practice. The relationship between design and implementation is seen in terms of the Set/Mass conceptual opposition. General Schemas Theory is used as a way of critiquing the dependence of Set based mathematics as a basis for Design. The dissertation delineates a new foundation for Systems Engineering as Emergent Engineering based on General Schemas Theory, and provides an advanced theory of Design based on the understanding of the meta-levels of Being, particularly focusing upon the relationship between Hyper Being and Wild Being in the context of Pure and Process Being. (shrink)

This paper explores the usefulness of the 'ethical matrix', proposed by Ben Mepham, as a tool in technology assessment, specifically in food ethics. We consider what the matrix is, how it might be useful as a tool in ethical decision-making, and what drawbacks might be associated with it. We suggest that it is helpful for fact-finding in ethical debates relating to food ethics; but that it is much less helpful in terms of weighing the different ethical problems that it uncovers. (...) Despite this drawback, we maintain that, with some modifications, the ethical matrix can be a useful tool in debates in food ethics. We argue that useful modifications might be to include future generations amongst the stakeholders in the matrix, and to substitute the principle of solidarity for the principle of justice. (shrink)

Philosophy of science and history of science both have a significant relation to science itself; but what is their relation to each other? That question has been a focal point of philosophical and historical work throughout the second half of this century. An analysis and review of the progress made in dealing with this question, and especially that made in philosophy, is the focus of this thesis. Chapter one concerns logical positivist and empiricist approaches to philosophy of science, and the (...) significance of the criticisms levelled at them by analytic epistemologists such as Willard Quine and 'historicist' philosophers, especially Thomas Kuhn. Chapter two details the attempts by Kuhn and Lakatos to integrate these historicist criticisms with historically oriented philosophy of science, in their separate attempts at providing rational explanations of historical developments. Kuhn's latest work seeks to mend fences with philosophy, but his efforts remain too closely tied to the epistemological approaches strongly criticized in his earlier work. Lakatos' treatment of history is much more subtle than most have understood it to be, but the conception of scientific rationality that arises out of it is transformed into an abstract cultural product, more reminiscent of Hegel's geist than of individual human rationality. Chapters three and four discuss the recommendations of Lakatos and Laudan to historians with regard to historiography, and the actual historiographies and philosophy of history of practicing historians and historians of science. The philosophers' contributions indicate little concern for the historians' own methods, materials, and purposes; and the historians' writings present methodologies for history of science that are independent of the normative demarcations of philosophy of science, pace Lakatos and Laudan. Chapter five develops a philosophical position that fosters a more productive engagement between philosophy and history of science, a 'methodological historicism' that embraces the possibility of an important role for social and political factors in a philosophical study of scientific development. The epistemological relativism that might accompany such a historicist position need not be the radical epistemological anarchism of Feyerabend, though it will allow for a significant underdetermination of scientific development by reason nonetheless. (shrink)

ChatGPT – a large language model – recently passed the U.S. bar exam. The startling rise and power of generative artificial intelligence (AI) systems such as ChatGPT lead us to consider whether and how more specialized systems could be used to overcome existing barriers to the legal system. Such systems could be employed in either of the two major stages of the pursuit of justice: preliminary information gathering and formal engagement with the state’s legal institutions and professionals. We focus on (...) the former and argue that developing and deploying publicly funded AI legal advisors can reduce economic and shame-based cultural barriers to the information-gathering stage of pursuing justice. (shrink)

How must we and the world be constituted if science is possible? René Descartes had some ideas: For example, he wrote in 1639 to Marin Mersenne, “The imagination, which is the part of the mind that most helps mathematics, is more of a hindrance than a help in metaphysical speculation.” In another missive he suggested that, “besides [local] memory, which depends on the body, I believe there is also another one, entirely intellectual, which depends on the soul alone” (pp. 59, (...) 52). Peter Schouls marshals brief passages such as these alongside discussions of Descartes’ major works to sketch a partial portrait of the human being and the universe. Schouls touches on both metaphysics and cognition, asking how things must be arranged to allow Descartes’ famous method to be mobilized. His conclusions run as follows. First, what should come as no surprise, Descartes “insists on a thoroughgoing dualism that allows him to characterize human beings as essentially free and to characterize nature as causally determined.” (44) Second, Schouls develops from Descartes’ cues a theory of cognition that allows for the pursuit of science by the exploitation of that free human creativity. ). Third, Schouls brings the previous points into full development with a speculative discussion of intellectual argument and scientific method. (shrink)

What is the scientist’s work? Philosophers may turn to theory and to its relation to observation; historians are more inclined to turn to the scientists themselves and the situation the scientists find themselves in. Why do scientists work as they do, and what effect does the world they inhabit have on their productivity and their product? Those are more the historians’ questions. They might appear to converge with the philosophers’ own in this: What does it take to be a successful (...) scientist? Yet the question of success also invites answers from a sociological perspective. The essay collection Scholars in Action supports a richly historical sociological foray into identifying and explaining the conditions for success at a particular moment and locus of Enlightenment thinking. (shrink)

In August of 2000, Firestone executives initiated the second largest tire recall in U.S. history. Many of the recalled tires had been installed as original factory equipment on the popular Ford Explorer SUVs. At the time of the recall, the tires and vehicles had been linked to numerous accidents and deaths, most of which occurred when tire blowouts resulted in vehicle rollovers. While Firestones role in this case has been widely acknowledged, Ford executives have managed to deflect much of the (...) attention away from themselves, mainly by claiming that the Firestone tires were not its product, and therefore not its responsibility. In this paper, we examine the extent to which Ford can be held morally responsible for the incidents at issue. In so doing, we develop an approach for determining when an item is a product in its own right, as opposed to a component of another product. We argue that such an analysis not only provides a better understanding of this case, but also more properly accounts for the extent to which evolutions in technology and business relationships can affect issues of moral responsibility in business contexts. (shrink)

Is the societal-level of analysis sufficient today to understand the values of those in the global workforce? Or are individual-level analyses more appropriate for assessing the influence of values on ethical behaviors across country workforces? Using multi-level analyses for a 48-society sample, we test the utility of both the societal-level and individual-level dimensions of collectivism and individualism values for predicting ethical behaviors of business professionals. Our values-based behavioral analysis indicates that values at the individual-level make a more significant contribution to (...) explaining variance in ethical behaviors than do values at the societal-level. Implicitly, our findings question the soundness of using societal-level values measures. Implications for international business research are discussed. (shrink)

Animal ethicists have recently debated the ethical questions raised by disenhancing animals to improve their welfare. Here, we focus on the particular case of breeding hens for commercial egg-laying systems to become blind, in order to benefit their welfare. Many people find breeding blind hens intuitively repellent, yet ‘welfare-only’ positions appear to be committed to endorsing this possibility if it produces welfare gains. We call this the ‘Blind Hens’ Challenge’. In this paper, we argue that there are both empirical and (...) theoretical reasons why even those adopting ‘welfare-only’ views should be concerned about breeding blind hens. But we also argue that alternative views, which (for example) claim that it is important to respect the telos or rights of an animal, do not offer a more convincing solution to questions raised by the possibility of disenhancing animals for their own benefit. (shrink)

En este texto se ofrece una interpretación del blues a la luz de la teoría del arte de Walter Benjamin y la teoría de la cultura de Bolívar Echeverría. El texto hace consideraciones sobre el blues, la música, la cultura y la reproducción social en general, a partir de lo cual se realiza un estudio de caso sobre la relación entre Junior Kimbrough y Robert Palmer y se sacan conclusiones respecto a la cultura del blues como fenómeno social.

In Just Fodder, Milburn argues for a relational account of our duties to animals. Following Clare Palmer, he argues that, though all animals have negative rights that we have a duty not to violate, we only gain positive obligations towards animals in the contexts of our relationships with them, which can be personal or political. He argues that human beings have collective positive duties towards domesticated animals, in virtue of the kind of relationship between us established by domestication. However, (...) when it comes to wild animals, he argues that we have no such morally relevant relationships, and so we have only negative duties towards them. I argue that throughout history and even prehistory human beings have morally entangled themselves with wild animals sufficiently that we may in fact have collective positive duties towards many, if not all, wild animals. (shrink)

Climate change increasingly impacts the resilience of ecosystems and agricultural production. On the one hand, changing weather patterns negatively affect crop yields and thus global food security. Indeed, we live in an age where more than one billion people are going hungry, and this number is expected to rise as climate-induced change continues to displace communities and thus separate them from their means of food production (Internal Displacement Monitoring Centre 2015). In this context, if one accepts a humancentric ethic, then (...) the focus would be on addressing impacts to agricultural production, and thus food security (Borlaug 1997; Navin 2012). On the other hand, ecological resilience is also being impacted by climate change, as species go extinct or migrate due to fluctuating temperatures and shifting weather patterns. This reduction of resilience negatively impacts ecosystem services and the ability of the natural world to support life (Palmer and Larson 2014; Urban 2015). From an environmental holist perspective, then, one could argue that the ethical path would be to focus on reducing negative impacts to species and/or local ecosystems rather than increasing crop yields. Thus, there appears to be a tension between the prioritization of crop yields and the mitigation of ecosystem impacts. While this tension is well established in the agricultural literature (Kirschenmann 2010; Noll 2018), climatezas lochange exacerbates the situation, as agricultural lands are stressed and climate-induced migrations increase already high demands for foodstuffs, thus bringing the conflict to the forefront (Macdonald et al. 2015; Food and Agriculture Organization of the United Nations 2017a). (shrink)

Feminist critics of evolutionary psychology are often accused of committing the naturalistic fallacy, that is, of inferring certain normative conclusions from evolutionary psychology’s purely descriptive accounts. This article refutes the accusation of the naturalistic fallacy, by showing that evolutionary psychology’s accounts of human behavior are not purely descriptive, but rather grounded on biased value judgments. A paradigmatic example is Randy Thornhill and Craig Palmer’s well-known book A Natural History of Rape. I argue that at least three biased judgments are (...) at work in Thornhill and Palmer’s evolutionary psychology account of rape: (1) adaptationist approaches to evolution, (2) willful ignorance of cultural and social context, and (3) binary understanding of gender and sex. In that Thornhill and Palmer’s account cannot hold without the three biased value judgments, it is not a purely factual description of rape. Therefore, feminist concerns over its normative implications do not commit the naturalistic fallacy, as it is not the case that they infer a normative conclusion from a pure description. (shrink)

In Animal Ethics in Context, Clare Palmer tries to harmonise two competing approaches to animal ethics. One focuses on the morally relevant capacities that animals possess. The other is the Laissez-Faire Intuition (LFI): the claim that we have duties to assist domesticated animals but should (at least generally) leave wild animals alone. In this paper, I critique the arguments that Palmer offers in favour of the No-Contact LFI - the view that we have (prima facie) duties not to (...) harm wild animals but no duties to assist them. I argue that Palmer's endorsement of the No-Contact LFI is unwarranted. Her arguments actually provide strong reasons to endorse what I call the Gradient View - a position that posits weak presumptive duties to assist wild animals that become stronger as our relations with the animals grow stronger. (shrink)

Descartes is notorious for holding a strong anti-vacuist position. On his view, according to the standard reading, empty space not only does not exist in nature, but it is logically impossible. The very notion of a void or vacuum is an incoherent one. Recently Eric Palmer has proposed a revisionist reading of Descartes on empty space, arguing that he is more sanguine about its possibility. Palmer makes use of Descartes’ early correspondence with Marin Mersenne, including his commentary on (...) Galileo’s Two New Sciences. I argue that Palmer’s reading is mistaken, and that it relies on an understandable but faulty inference—i.e., that if Descartes considers the implications of an opposing view, he must find it at least coherent. Descartes, as I show from his correspondence and other texts, uses a variety of persuasive strategies, and levels charges of different logical strength, against positions which he takes to be incoherent. Thus we cannot infer from the fact that Descartes argues, e.g., that something is a superfluous theoretical entity, that he admits that entity’s coherence. He often chooses to argue a weaker thesis against an opponent so that he can use an argument to which the opponent is more likely to agree. (shrink)

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

According to the Dilemma Defense, it is question-begging against the incompatibilist defender of the principle of alternative possibilities (PAP) to assume that the agent in a deterministic Frankfurt-style case (FSC) cannot do otherwise in light of causal determinism, but is nevertheless morally responsible. As a result, Fischer (Philos Rev 119:315–336, 2010; Analysis 73:489–496, 2013) attempts to undermine PAP in a different manner via a deterministic FSC. More specifically, Fischer attempts to show that if causal determinism rules out an agent’s moral (...) responsibility, it is not in virtue of its eliminating the agent’s alternative possibilities. I contend that, once we focus upon the distinction between entailment and explanation, the incompatibilist defender of PAP can successfully rebut Fischer’s argument. I argue for this claim while granting Fischer a number of assumptions that only render a defense of PAP more difficult. Additionally, I cast doubt upon Palmer’s (Synthese 191:3847–3864, 2014) critique of Fischer’s argument, which in turn renders my defense of PAP all the more critical. (shrink)