I distinguish between the nineteenth- to twentieth-century (modernist) tendency to rehabilitate (white) femininity from the abject popular, and the twentieth- to twenty-first-century (postmodernist) tendency to rehabilitate the popular from abject white femininity. Careful attention to the role of nineteenth-century racial politics in Nietzsche's Gay Science shows that his work uses racial nonwhiteness to counter the supposedly deleterious effects of (white) femininity (passivity, conformity, and so on). This move—using racial nonwhiteness to rescue pop culture from white femininity—is a common twentieth- and (...) twenty-first-century practice. I use Nietzsche to track shifts from classical to neo-liberal methods of appropriating “difference.” Hipness is one form of this neoliberal approach to difference, and it is exemplified by the approach to race, gender, and pop culture in Vincente Minnelli's film The Band Wagon. I expand upon Robert Gooding-Williams's reading of this film, and argue that mid-century white hipness dissociates the popular from femininity and whiteness, and values the popular when performed by white men “acting black.” Hipness instrumentalizes femininity and racial nonwhiteness so that any benefits that might come from them accrue only to white men, and not to the female and male artists of color whose works are appropriated. (shrink)

J. C. Nyiri has argued in a series of papers that Ludwig Wittgenstein is a conservative philosopher. In ‘Wittgenstein 1929-31: The Turning Back’ Nyiri cites Wittgenstein’s admiration for Grillparzer as well as overtly philosophical passages from On Certainty in support of that thesis. I argue, in opposition to Nyiri, that we should separate Wittgenstein’s political remarks from his philosophical remarks and that nothing Wittgenstein says in his philosophical work obviously implies a conservative viewpoint, or any other kind of political viewpoint. (...) In his philosophical work Wittgenstein was concerned with untangling conceptual confusions rather than with putting forward a political viewpoint and the two kinds of activities are quite different. There is, however, some evidence of elements of conservatism in the stances that Wittgenstein took on political issues although there is also some evidence of sympathy for left-wing views, particularly during the ‘late’ period of Wittgenstein’s work after he returned to philosophy at the end of the 1920s. Wittgenstein’s philosophical work cannot be claimed by people of any particular political persuasion as their own but it can be used to untangle philosophical problems in the work of a great variety of political philosophies. (shrink)

Loneliness is a near-universal experience. It is particularly common for individuals with (so-called) psychopathological conditions or disorders. In this paper, we explore the experiential character of loneliness, with a specific emphasis on how social goods are experienced as absent in ways that involve a diminished sense of agency and recognition. We explore the role and experience of loneliness in three case studies: depression, anorexia nervosa, and autism. We demonstrate that even though experiences of loneliness might be common to many psychopathologies, (...) these experiences nevertheless have distinctive profiles. Specifically, we suggest that: (i) loneliness is often a core characteristic of depressive experience; (ii) loneliness can drive, and even cement, disordered eating practices and anorectic identity in anorexia nervosa; iii) loneliness is neither a core characteristic of autism nor a driver but is rather commonly experienced as stemming from social worlds, environments, and norms that fail to accommodate autistic bodies and their distinctive forms of life. We aim to do justice to the pervasiveness of loneliness in many — if not all — psychopathologies, while also highlighting the need to attend to psychopathology-specific experiences of loneliness, agency, and (non-)recognition. (shrink)

As technology improves, artificial systems are increasingly able to behave in human-like ways: holding a conversation; providing information, advice, and support; or taking on the role of therapist, teacher, or counsellor. This enhanced behavioural complexity, we argue, encourages deeper forms of affective engagement on the part of the human user, with the artificial agent helping to stabilise, subdue, prolong, or intensify a person’s emotional condition. Here, we defend a fictionalist account of human/AI interaction, according to which these encounters involve an (...) elaborate practise of imaginative pretence: a make-believe in which the artificial agent is attributed a life of its own. We attend, specifically, to the temporal characteristics of these fictions, and to what we imagine artificial agents are doing when we are not looking at them. (shrink)

In addiction, apparently causally significant phenomena occur at a huge number of levels; addiction is affected by biomedical, neurological, pharmacological, clinical, social, and politico-legal factors, among many others. In such a complex, multifaceted field of inquiry, it seems very unlikely that all the many layers of explanation will prove amenable to any simple or straightforward, reductive analysis; if we are to unify the many different sciences of addiction while respecting their causal autonomy, then, what we are likely to need is (...) an integrative framework. In this paper, we propose the theory of “Externalist” or “4E” – for extended, embodied, embedded, and enactive – cognition, which focuses on the empirical and conceptual centrality of the wider extra-neural environment to cognitive and mental processes, as a candidate for such a framework. We begin in Section 2 by outlining how such a perspective might apply to psychiatry more generally, before turning to some of the ways it can illuminate addiction in particular: Section 3 points to a way of dissolving the classic dichotomy between the “choice model” and “disease model” in the addiction literature; Section 4 shows how 4E concepts can clarify the interplay between the addict’s brain and her environment; and Section 5 considers how these insights help to explain the success of some recovery strategies, and may help to inform the development of new ones. (shrink)

Potentialism is the view that the universe of sets is inherently potential. It comes in two main flavours: height-potentialism and width-potentialism. It is natural to think that height and width potentialism are just aspects of a broader phenomenon of potentialism, that they might both be true. The main result of this paper is that this is mistaken: height and width potentialism are jointly inconsistent. Indeed, I will argue that height potentialism is independently committed to an ultimate background universe of sets, (...) an ultimate V, up to its height. (shrink)

Johnston famously argued that the colors are, more or less inclusively speaking, dispositions to cause color experiences by arguing that this view best accommodates his five proposed core beliefs about color. Since then, Campbell, Kalderon, Gert, Benbaji, and others, have all engaged with at least some of Johnston’s proposed core beliefs in one way or another. Which propositions are core beliefs is ultimately an empirical matter. We investigate whether Johnston’s proposed core beliefs are, in fact, believed by assessing the agreement/disagreement (...) of non-philosophers with them. Two experiments are run each with large sample sizes, the second designed to address criticisms of the first. We find that non-philosophers mostly agree with the proposed core beliefs, but that they agree with some more than others. (shrink)

I present a novel view on the nature of time: primitivism. This view is the conjunction of two theses: that presence is concreteness and that the present changes, where change is a fundamental process that cannot be analyzed. After explaining this view in-depth, I look at how it explains the flow of time and solves many puzzles, for example, McTaggart’s famous paradox about the unreality of time.

Objectification involves treating someone as a thing. The role of images in perpetuating objectification has been discussed by feminist philosophers. However, the precise effect that images have on an individual's visual system is seldom explored. Kathleen Stock’s work is an exception—she describes certain images of women as causing viewers to develop an objectifying ‘gestalt’ which is then projected onto real-life women. However, she doesn’t specify the level of visual processing at which objectification occurs. In this paper, I propose that images (...) can affect a viewer's early visual system. I will argue that if a viewer is exposed to a lot of images that depict women as sexual objects, this will bias their early visual selection mechanisms in a way that can result in an objectifying way of seeing. This is an important contribution to work on objectification as it incorporates empirical studies on vision and findings from philosophy of mind. It also examines some of the epistemic and moral consequences of objectification occurring at this early visual stage. (shrink)

In the present article, I show that sounds are properties that are not physical in a narrow sense. First, I argue that sounds are properties using Moorean style arguments and defend this property view from various arguments against it that make use of salient disanalogies between sounds and colors. The first disanalogy is that we talk of objects making sounds but not of objects making colors. The second is that we count and quantify over sounds but not colors. The third (...) is that sounds can survive qualitative change in their auditory properties, but colors cannot survive change in their chromatic properties. Next, I provide a taxonomy of property views of sound. As the property view of sound has been so rarely discussed, many of the views available have never been articulated. My taxonomy will articulate these views and how they are related to one another. I taxonomize sounds according to three characteristics: dispositional/non-dispositional, relational/non-relational, and reductive/non-reductive. Finally, mirroring a popular argument in the color literature, I argue that physical views in the narrow sense are unable to accommodate the similarity and difference relations in which sounds essentially stand. I end replying to three objections. (shrink)

This article is on a precise kind of color primitivism, ‘ostensivism.’ This is the view that it is in the nature of the colors that they are phenomenal, non-reductive, structural, categorical properties. First, I differentiate ostensivism from other precise forms of primitivism. Next, I examine the core belief ‘Revelation,’ and propose a revised version, which, unlike standard statements, is compatible with a yet unstated but plausible core belief: roughly, that there are interesting things to be discovered about the nature of (...) the colors. Finally, I show that ostensivism is the only view on color that can accommodate both proposed core beliefs. (shrink)

This article documents our collaborative ongoing struggle to disrupt the reproduction of the coloniality of knowledge in the teaching of Gender Studies. We document how our decolonial feminist activism is actualised in our pedagogy, which is guided by feminist interpretations of ‘wonder’ (Irigaray, 1999; Ahmed, 2004; hooks, 2010) read alongside decolonial theory, including that of Ramón Grosfoguel, Walter D. Mignolo and María Lugones. Using notions of wonder as pedagogy, we attempt to create spaces in our classrooms where critical self-reflection and (...) critical intellectual and embodied engagement can emerge. Our attempts to create these spaces include multiple aspects or threads that, when woven together, might enable other ways of knowing-being-doing that works towards disrupting feminist complicity with coloniality in the Australian context. (shrink)

(NOTE: This is a transcript of the class. FOR THE FULL PAPER please click on "Maxson J McDowell" above.) An edited transcript of an experiment performed within a class on dream interpretation. Knowing only the dreamer’s age and gender, we interpreted his dream from its text. Our interpretation included predictions about the dreamer's psychological issues, and about his defenses. It also identified a series of jokes within the dream which would tend to penetrate the dreamer's defenses. When we had finished (...) our 'blind' interpretation, the bringer of the dream gave us more information about the dreamer against which we tested the accuracy of our predictions. A paper on this experiment has been submitted for publication. (shrink)

In an online, participatory class, we interpreted The Dream of the White House knowing nothing of the dreamer and having none of the dreamer’s associations. Our interpretation included a series of falsifiable predictions about the dreamer. When it was complete, we asked the bringer of the dream (who had until then been silent and was not visible to us) to give us more information about the dreamer. Of 17 predictions 15 were confirmed. The dreamer suffers dislocation and loss until she (...) asks a female manager for help. This record is another iteration of an experiment that will be described more fully in the paper 'The Dream of the Six-Legged Dog: An Experimental System to Test Meaning,' soon to be published. This iteration repeats and confirms the evidence given in that paper. More than any of the other iterations, it details how talk therapy promotes personality reorganization. It then supports these observations with experimental evidence. Because it demonstrates how talk therapy works, this iteration supports talk therapy against pressure from the drug and insurance corporations. AUDIO-RECORDING OF WHOLE CLASS: link provided on first page of the paper you download here. (shrink)

We present experimental evidence that an interpretation was accurate. Current wisdom notwithstanding, we could interpret from the text alone because its information is redundant: repetition provides internal checks. Knowing neither dreamer nor their associations we made falsifiable predictions that we tested by subsequently gathering information about the dreamer. Predictions were supported. Results were repeated with seven additional dreams. Each dream was tightly crafted, used humor, drama or hyperbole to penetrate the dreamer’s defenses, and furthered the emergence of personality. Our experiment (...) compliments fMRI and statistics because it studies a whole text as a unique narrative: one iteration identified healing steps during therapy; another confirmed the psychological meaning of a myth. Our experiment might generate a body of objective knowledge about interpretation and make interpretation itself more accurate. In the US 20% live with mental illness. Our experiment supports talk therapy against pressure from the drug and insurance industries. (shrink)

In an online, participatory class, we interpreted The Dream of the Tabby Cats knowing nothing of the dreamer beyond age and gender, and having none of the dreamer’s associations. Our interpretation included a series of predictions about the dreamer. When it was complete, we asked the bringer of the dream (who had until then been silent and was not visible to us) to give us more information about the dreamer. Later the dreamer herself gave us more information. Of six predictions (...) four were confirmed. The dreamer’s apartment is repeatedly disturbed and, each time, a new cat appears. This record is another iteration of an experiment that will be described more fully in the paper The Dream of the Six-Legged Dog: An Experimental System to Test Meaning, soon to be published. This iteration repeats and confirms the evidence given in that paper. AUDIO RECORD OF CLASS AVAILABLE: link is on first page of the paper you download from this page. (shrink)

(NOTE: This is a transcript of the class. FOR THE FULL PAPER, please click on "Maxson J. McDowell".) A complete transcript of an experiment performed within a class on dream interpretation. Knowing only the dreamers age and gender, we interpreted his dream from its text. Our interpretation included predictions about the dreamer's psychological issues, and about his defenses. It also identified a series of jokes within the dream which would tend to penetrate the dreamer's defenses. When we had finished our (...) 'blind' interpretation, the bringer of the dream gave us more information about the dreamer against which we tested the accuracy of our predictions. A paper on this experiment has been submitted for publication. A link to an AUDIO-RECORDING of this class is given on the first page of this transcript. (shrink)

In an online, participatory class, we interpreted The Dream of the Flaming Sword knowing nothing of the dreamer beyond age and gender, and having none of the dreamer’s associations. Our interpretation included a series of predictions about the dreamer. When it was complete, we asked the bringer of the dream (who had until then been silent and who also gave no visual feedback to our discussion) to give us more information about the dreamer. Eight months later the bringer gave us (...) further information from the dreamer. Our predictions were mostly confirmed. In the dream, the dreamer’s identity is repeatedly questioned. -/- This record is another iteration of an experiment that is described more fully in the paper The Dream of the Six-Legged Dog, soon to be published. This iteration repeats and confirms the evidence given in that paper. -/- AUDIO RECORD OF THE CLASS ABOUT THE FLAMING SWORD: link is on the title page of the paper you can download here. (shrink)

Intrapersonal variation due to color contrast effects has been used to argue against the following intuitive propositions about the colors: No object can be more than one determinable or determinate color of the same grade all over at the same time ; external objects are actually colored ; and the colors of objects are mind-independent. In this article, I provide a defense of Incompatibility, Realism, and Objectivism from intrapersonal variation arguments that rely on color contrast effects. I provide a novel, (...) ecumenical response to such arguments according to which typical variants are right, and which respects Incompatibility, Realism, and Objectivism, using the thesis that the colors of objects depend on the colors of objects in their surrounds. (shrink)

In an online, participatory class, we interpreted The Dream of Mercury knowing nothing of the dreamer and having none of the dreamer’s associations. Our interpretation included a series of falsifiable predictions about the dreamer. When it was complete, we asked the bringer of the dream (who had until then been silent and was not visible to us) to give us more information about the dreamer. The dreamer is instructed to confront a friendship he had abandoned and, when he does so, (...) is frightened by the inner life he discovers. This record is another iteration of an experiment that will be described more fully in the paper 'The Dream of the Six-Legged Dog: An Experimental System to Test Meaning,' soon to be published. This iteration repeats and confirms the evidence given in that paper. AN AUDIO-RECORD OF COMPLETE CLASS: link is given on first page of the paper you download here. (shrink)

This paper integrates symbolic thought and experimental research. We hypothesized that symbolic narratives provide homeostasis for the complex adaptive system that is personality. Our interpretation of a dream was based, in part, on this hypothesis. We found that the dream retold the myth of Saturn. When, by direct experiment, we tried to falsify our interpretation, our results supported our interpretation and thereby supported our hypothesis. Previously, evidence for this hypothesis had been only anecdotal. __________________________________________ For an audio-record of entire class: (...) link is given on 1st page of the text you download from this page. (shrink)

In an online, participatory class, we interpreted 'The Dream of Geese Nesting in Trees' knowing nothing of the dreamer beyond age and gender, and having none of the dreamer’s associations. Our interpretation included predictions about the dreamer. When it was complete, we asked the bringer of the dream (who had until then been mostly silent and who also gave no visual feedback to our discussion) to give us more information about the dreamer. Our main predictions were confirmed. Goslings are falling (...) on the dreamer’s head. This record is another iteration of an experiment that will be described more fully in the paper, 'The Dream of the Six-Legged Dog: An Experimental System that Tests Meaning,' soon to be published. This iteration repeats and confirms the evidence given in that paper. AUDIO RECORD OF COMPLETE CLASS: link is at top of paper you can download from this page. (shrink)

In this contribution in honour of Paul Busch, we criticise the claims of many expositions that the time-energy uncertainty principle allows both a violation of energy conservation and particle creation, provided that this happens for a sufficiently short time. But we agree that there are grains of truth in these claims: which we make precise and justify using perturbation theory.

Research on the ethics of algorithms has grown substantially over the past decade. Alongside the exponential development and application of machine learning algorithms, new ethical problems and solutions relating to their ubiquitous use in society have been proposed. This article builds on a review of the ethics of algorithms published in 2016, 2016). The goals are to contribute to the debate on the identification and analysis of the ethical implications of algorithms, to provide an updated analysis of epistemic and normative (...) concerns, and to offer actionable guidance for the governance of the design, development and deployment of algorithms. (shrink)

Draft version of essay. ABSTRACT: Benjamin Whichcote developed a distinctive account of human nature centered on our moral psychology. He believed that this view of human nature, which forms the foundation of “Cambridge Platonism,” showed that the demands of reason and faith are not merely compatible but dynamically supportive of one another. I develop an interpretation of this oft-neglected and widely misunderstood account of human nature and defend its viability against a key objection.

It is argued that colour name strategy, object name strategy, and chunking strategy in memory are all aspects of the same general phenomena, called stereotyping, and this in turn is an example of a know-how representation. Such representations are argued to have their origin in a principle called the minimum duplication of resources. For most the subsequent discussions existence of colour name strategy suffices. It is pointed out that the BerlinA- KayA universal partial ordering of colours and the frequency of (...) traffic accidents classified by colour are surprisingly similar; a detailed analysis is not carried out as the specific colours recorded are not identical. Some consequences of the existence of a name strategy for the philosophy of language and mathematics are discussed: specifically it is argued that in accounts of truth and meaning it is necessary throughout to use real numbers as opposed to bi-valent quantities; and also that the concomitant label associated with sentences should not be of unconditional truth, but rather several real-valued quantities associated with visual communication. The implication of real-valued truth quantities is that the Continuum Hypothesis of pure mathematics is side-stepped, because real valued quantities occur ab initio. The existence of name strategy shows that thought/sememes and talk/phonemes can be separate, and this vindicates the assumption of thought occurring before talk used in psycho-linguistic speech production models. (shrink)

The empirical phenomenon at the center of this paper is projection, which we define (uncontroversially) as follows: (1) Definition of projection An implication projects if and only if it survives as an utterance implication when the expression that triggers the implication occurs under the syntactic scope of an entailment-cancelling operator. Projection is observed, for example, with utterances containing aspectual verbs like stop, as shown in (2) and (3) with examples from English and Paraguayan Guaraní (Paraguay, Tupí-Guaraní).1 The Guaraní example in (...) (2) and its English translation have at least the following implications: (i) Carla has previously smoked, and (ii) Carla stopped smoking. The first but not the second of these implications is also conveyed by the question version of sentence (2), as in (3a), or when (2) is embedded under entailment-cancelling sentential operators, such as negation, as in (3b), the antecedent of a conditional, as in (3c), or an epistemic modal, as in (3d). Hence, by the definition in (14), the first but not the second implication of (2) projects. (shrink)

Attention Deficit Hyperactivity Disorder (ADHD) continues to be controversial with arguments for and against its veracity being waged by individuals representing a variety of disciplines from behavioral scientists to philosophers. Our perspective focuses on the epistemological underpinnings of what is now commonly known as ADHD. Its ignominious history and current disputes may stem from a "pessimistic" epistemology, meaning that truth is only the province of persons in authority and power. The authoritative organizations that govern the diagnostic labels and criteria are (...) the American Psychiatric Association and their Diagnostic and Statistical Manual and the World Health Organization that sponsors the International Classification of Disease. We contrast the pessimistic epistemology with criteria for truth from the scientific method. Although scientific scrutiny has been and is being applied subsequent to "authoritarian edicts" of the disorder, we opine that ADHD currently does not have status beyond that of the "hypothetical construct." Moreover, current brain-based causal models have failed to provide rigorous supporting data that comes from testing falsifiable hypotheses. (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. Londres: Cambridge University Press, 1972. BRONSON, Franklin H. Mammalian reproductive biology. Chicago: University of Chicago Press, 1989. BUEHR, Mia. The primordial germ cells of mammals: some current perspectives. Experimental cell research, v. 232, n. 2, p. 194-207, 1997. BYSKOV, Anne G. Differentiation of mammalian embryonic gonad. Physiological reviews, v. 66, n. 1, p. 71-117, 1986. CAPEL, Blanche et al. Migration of mesonephric cells into the mammalian gonad depends on Sry. Mechanisms of development, v. 84, n. 1-2, p. 127-131, 1999. CAPEL, Blanche. The battle of the sexes. Mechanisms of development, v. 92, n. 1, p. 89-103, 2000. DERIVAUX, Jules; BARNABÉ, Renato Campanarut. Reprodução dos animais domésticos. Zaragoza: Acribia, 1980. DOMENICE, Sorahia et al. Aspectos moleculares da determinação e diferenciação sexual. Arquivos Brasileiros de Endocrinologia & Metabologia, v. 46, n. 4, p. 433-443, 2002. DONAHOE, Patricia K. et al. Mullerian inhibiting substance activity in bovine fetal, newborn and prepubertal testes. Biology of reproduction, v. 16, n. 2, p. 238-243, 1977. HAFEZ, Elsayed Saad Eldin; HAFEZ, B. Reprodução animal. São Paulo: Manole, 2004. HANLEY, Neil A. et al. Steroidogenic factor 1 (SF-1) is essential for ovarian development and function. Molecular and cellular endocrinology, v. 163, n. 1-2, p. 27-32, 2000. HIORT, Olaf; PAUL-MARTIN, H. The molecular basis of male sexual differentiation. European journal of endocrinology, v. 142, n. 2, p. 101-110, 2000. HOLY, Lubos; MARTÍNEZ JÚSTIZ, G. Colab. Biología de la reproducción bovina. Havana: Revolucionária, 1975. JOSSO, Nathalie et al. The role of anti-Müllerian hormone in gonadal development. Molecular and cellular endocrinology, v. 145, n. 1-2, p. 3-7, 1998. JOST, Alfred et al. Studies on sex differentiation in mammals. In: Proceedings of the 1972 Laurentian Hormone Conference. Londres: Academic Press, 1973. p. 1-41. KNOBIL, Ernst. Knobil and Neill's physiology of reproduction. EUA: Gulf Professional Publishing, 2006. KOFMAN ALFARO, S.; MERCHANT LARIOS, H.; PEREZ PALACIOS, G. Diferenciacion sexual. I. Bases biologicas del dimorfismo sexual. Rev. invest. clín, p. 349-59, 1982. KOOPMAN, Peter. Sry and Sox9: mammalian testis-determining genes. Cellular and Molecular Life Sciences CMLS, v. 55, n. 6-7, p. 839-856, 1999. MCDONALD, L. E. Veterinary endocrinology. Lea & Febiger, Philadelphia, Pa, 1969. MEIZEL, S.; JOHNSON, M. H. Development in mammals. MH Johnson, Ed, v. 3, p. 1-64, 1978. MELLO, Maricilda Palandi de; ASSUMPÇÃO, Juliana de G.; HACKEL, Christine. Genes envolvidos na determinação e diferenciação do sexo. Arquivos Brasileiros de Endocrinologia & Metabologia, v. 49, n. 1, p. 14-25, 2005. -/- REFERÊNCIAS BIBLIOGRÁFICAS MERCHANT-LARIOS, H. Ovarian differentiation. The Vertebrate Ovary, p. 47-81, 1978. MIES FILHO, Antonio. Reprodução dos animais. Porto Alegre: Sulina, 1987. NEF, Serge; PARADA, Luis F. Hormones in male sexual development. Genes & Development, v. 14, n. 24, p. 3075-3086, 2000. PARKER, Keith L.; SCHEDL, Andreas; SCHIMMER, Bernard P. Gene interactions in gonadal development. Annual review of physiology, v. 61, n. 1, p. 417-433, 1999. SWAIN, Amanda; LOVELL-BADGE, Robin. Mammalian sex determination: a molecular drama. Genes & development, v. 13, n. 7, p. 755-767, 1999. WILHELM, Dagmar; PALMER, Stephen; KOOPMAN, Peter. Sex determination and gonadal development in mammals. Physiological reviews, v. 87, n. 1, p. 1-28, 2007. WILSON, Jean D.; GRIFFIN, James E.; GEORGE, Fredrick W. Sexual differentiation: early hormone synthesis and action. Biology of reproduction, v. 22, n. 1, p. 9-17, 1980. -/- Emanuel Isaque Cordeiro da Silva Belo Jardim, 07 de Maio de 2020. (shrink)

The Protein Ontology (PRO) provides a formal, logically-based classification of specific protein classes including structured representations of protein isoforms, variants and modified forms. Initially focused on proteins found in human, mouse and Escherichia coli, PRO now includes representations of protein complexes. The PRO Consortium works in concert with the developers of other biomedical ontologies and protein knowledge bases to provide the ability to formally organize and integrate representations of precise protein forms so as to enhance accessibility to results of protein (...) research. PRO (http://pir.georgetown.edu/pro) is part of the Open Biomedical Ontologies (OBO) Foundry. (shrink)

Why is gauge symmetry so important in modern physics, given that one must eliminate it when interpreting what the theory represents? In this paper we discuss the sense in which gauge symmetry can be fruitfully applied to constrain the space of possible dynamical models in such a way that forces and charges are appropriately coupled. We review the most well-known application of this kind, known as the 'gauge argument' or 'gauge principle', discuss its difficulties, and then reconstruct the gauge argument (...) as a valid theorem in quantum theory. We then present what we take to be a better and more general gauge argument, based on Noether's second theorem in classical Lagrangian field theory, and argue that this provides a more appropriate framework for understanding how gauge symmetry helps to constrain the dynamics of physical theories. (shrink)

Philosophers of technology have identified various mechanisms through which technology can change moral norms, values, beliefs and practices. Danaher and Sætra ( 2023 ) offer a useful systematization of these mechanisms, with no claim to being exhaustive. We contribute to their work by analyzing how the mediating role of moral concepts fits into this scheme. First, we point out that concepts mediate the moral effects of technological changes, a process we call conceptual mediation. We illustrate this with the concepts of (...) ‘brain death’ and ‘reproductive autonomy’, whose moral implications crystallized in the interplay with new medical technologies. Subsequently, we argue that conceptual mediation is best understood as a type of second-order mediation, which channels the moral implications of the first-order technological mediations identified by Danaher and Sætra (decisional, relational, perceptual). We conclude that second-order mediation plays a central and underappreciated role in processes of technomoral change. (shrink)

Purpose This paper aims to formalize long-term trajectories of human civilization as a scientific and ethical field of study. The long-term trajectory of human civilization can be defined as the path that human civilization takes during the entire future time period in which human civilization could continue to exist. -/- Design/methodology/approach This paper focuses on four types of trajectories: status quo trajectories, in which human civilization persists in a state broadly similar to its current state into the distant future; catastrophe (...) trajectories, in which one or more events cause significant harm to human civilization; technological transformation trajectories, in which radical technological breakthroughs put human civilization on a fundamentally different course; and astronomical trajectories, in which human civilization expands beyond its home planet and into the accessible portions of the cosmos. -/- Findings Status quo trajectories appear unlikely to persist into the distant future, especially in light of long-term astronomical processes. Several catastrophe, technological transformation and astronomical trajectories appear possible. -/- Originality/value Some current actions may be able to affect the long-term trajectory. Whether these actions should be pursued depends on a mix of empirical and ethical factors. For some ethical frameworks, these actions may be especially important to pursue. (shrink)

Representing species-specific proteins and protein complexes in ontologies that are both human and machine-readable facilitates the retrieval, analysis, and interpretation of genome-scale data sets. Although existing protin-centric informatics resources provide the biomedical research community with well-curated compendia of protein sequence and structure, these resources lack formal ontological representations of the relationships among the proteins themselves. The Protein Ontology (PRO) Consortium is filling this informatics resource gap by developing ontological representations and relationships among proteins and their variants and modified forms. Because (...) proteins are often functional only as members of stable protein complexes, the PRO Consortium, in collaboration with existing protein and pathway databases, has launched a new initiative to implement logical and consistent representation of protein complexes. We describe here how the PRO Consortium is meeting the challenge of representing species-specific protein complexes, how protein complex representation in PRO supports annotation of protein complexes and comparative biology, and how PRO is being integrated into existing community bioinformatics resources. The PRO resource is accessible at http://pir.georgetown.edu/pro/. (shrink)

Despite the frequency of stillbirths, the subsequent implications are overlooked and underappreciated. We present findings from comprehensive, systematic literature reviews, and new analyses of published and unpublished data, to establish the effect of stillbirth on parents, families, health-care providers, and societies worldwide. Data for direct costs of this event are sparse but suggest that a stillbirth needs more resources than a livebirth, both in the perinatal period and in additional surveillance during subsequent pregnancies. Indirect and intangible costs of stillbirth are (...) extensive and are usually met by families alone. This issue is particularly onerous for those with few resources. Negative effects, particularly on parental mental health, might be moderated by empathic attitudes of care providers and tailored interventions. The value of the baby, as well as the associated costs for parents, families, care providers, communities, and society, should be considered to prevent stillbirths and reduce associated morbidity. (shrink)

In an online, participatory class, we interpreted 'The Dream of the Three Orcas' knowing nothing of the dreamer beyond age and gender, and having none of the dreamer’s associations. -/- Our interpretation included nine predictions about the dreamer. When it was complete, we asked the bringer of the dream (who had not been present before our interpretation was complete) to give us more information about the dreamer. Later the dreamer also gave us more information. Our predictions were mostly confirmed. The (...) dreamer is standing on beach when huge orca-like floats appear. -/- This record is another iteration of an experiment that is described more fully in the paper 'The Dream of the Six-Legged Dog: An Experimental System that Tests Symbolic Meaning,' soon to be published. This iteration repeats and confirms the evidence given in that paper. ONLINE AUDIO RECORD OF ENTIRE ORCAS' CLASS : link is on title page of the paper you can download here. (shrink)

In this paper, we defend two main claims. The first is a moderate claim: we have a negative duty to not use binary gender-specific pronouns he or she to refer to genderqueer individuals. We defend this with an argument by analogy. It was gravely wrong for Mark Latham to refer to Catherine McGregor, a transgender woman, using the pronoun he; we argue that such cases of misgendering are morally analogous to referring to Angel Haze, who identifies as genderqueer, as he (...) or she. The second is a radical claim: we have a negative duty to not use any gender-specific pronouns to refer to anyone, regardless of their gender identity. We offer three arguments in favor of this claim (which appeal to concerns about inegalitarianism and risk, invasions of privacy, and reinforcing essentialist ideologies). We also show why the radical claim is compatible with the moderate claim. Before concluding, we examine common concerns about incorporating either they or a neologism such as ze as a third-person singular gender-neutral pronoun. These concerns, we argue, do not provide sufficient reason to reject either the moderate or radical claim. (shrink)

Replicating or exceeding human intelligence, not just in particular domains but in general, has always been a major goal of Artificial Intelligence (AI). We argue here that “human intelligence” is not only ill-defined, but often conflated with broader aspects of human psychology. Standard arguments for replicating it are morally unacceptable. We then suggest a reframing: that the proper goal of AI is not to replicate humans, but to complement them by creating diverse intelligences capable of collaborating with humans. This goal (...) renders issues of theory of mind, empathy, and caring, or community engagement, central to AI. It also challenges AI to better understand the circumstances in which human intelligence, including human moral intelligence, fails. (shrink)

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: -/- The main aim of this review will be to assess the effects of changing practitioner empathy or patient expectations for all conditions. The main objective is to conduct a systematic review of randomised trials where the intervention involves manipulating either (a) practitioner empathy or (b) patient expectations, or (c) both.

Extant theoretical work on the political resource curse implies that dependence on resource revenues should decrease autocracies’ likelihood of democratizing but not necessarily affect democracies’ chances of survival. Yet most previous empirical studies estimate models that are ill-suited to address this claim. We improve upon earlier studies, estimating a dynamic logit model that interacts a continuous measure of resource dependence with an indicator of regime type using data from 166 countries, covering the period from 1816-2006. We find that an increase (...) in resource dependence at time t - 1 increases the likelihood of autocratic persistence at t, but has no appreciable effect on democratic survival. We go beyond existing empirical studies to show that increases in resource dependence have persistent and substantial cumulative effects on autocracies' likelihood of becoming democratic over the long-term, showing that the total effect of resource dependence on regime type is much larger than the short-term (one period) effect indicates. (shrink)

This volume celebrates the various facets of Alan Turing (1912–1954), the British mathematician and computing pioneer, widely considered as the father of computer science. It is aimed at the general reader, with additional notes and references for those who wish to explore the life and work of Turing more deeply. -/- The book is divided into eight parts, covering different aspects of Turing’s life and work. -/- Part I presents various biographical aspects of Turing, some from a personal point of (...) view. -/- Part II presents Turing’s universal machine (now known as a Turing machine), which provides a theoretical framework for reasoning about computation. His 1936 paper on this subject is widely seen as providing the starting point for the field of theoretical computer science. -/- Part III presents Turing’s working on codebreaking during World War II. While the War was a disastrous interlude for many, for Turing it provided a nationally important outlet for his creative genius. It is not an overstatement to say that without Turing, the War would probably have lasted longer, and may even have been lost by the Allies. The sensitive nature of Turning’s wartime work meant that much of this has been revealed only relatively recently. -/- Part IV presents Turing’s post-War work on computing, both at the National Physical Laboratory and at the University of Manchester. He made contributions to both hardware design, through the ACE computer at the NPL, and software, especially at Manchester. Part V covers Turing’s contribution to machine intelligence (now known as Artificial Intelligence or AI). Although Turing did not coin the term, he can be considered a founder of this field which is still active today, authoring a seminal paper in 1950. -/- Part VI covers morphogenesis, Turing’s last major scientific contribution, on the generation of seemingly random patterns in biology and on the mathematics behind such patterns. Interest in this area has increased rapidly in recent times in the field of bioinformatics, with Turing’s 1952 paper on this subject being frequently cited. -/- Part VII presents some of Turing’s mathematical influences and achievements. Turing was remarkably free of external influences, with few co-authors – Max Newman was an exception and acted as a mathematical mentor in both Cambridge and Manchester. -/- Part VIII considers Turing in a wider context, including his influence and legacy to science and in the public consciousness. -/- Reflecting Turing’s wide influence, the book includes contributions by authors from a wide variety of backgrounds. Contemporaries provide reminiscences, while there are perspectives by philosophers, mathematicians, computer scientists, historians of science, and museum curators. Some of the contributors gave presentations at Turing Centenary meetings in 2012 in Bletchley Park, King’s College Cambridge, and Oxford University, and several of the chapters in this volume are based on those presentations – some through transcription of the original talks, especially for Turing’s contemporaries, now aged in their 90s. Sadly, some contributors died before the publication of this book, hence its dedication to them. -/- For those interested in personal recollections, Chapters 2, 3, 11, 12, 16, 17, and 36 will be of interest. For philosophical aspects of Turing’s work, see Chapters 6, 7, 26–31, and 41. Mathematical perspectives can be found in Chapters 35 and 37–39. Historical perspectives can be found in Chapters 4, 8, 9, 10, 13–15, 18, 19, 21–25, 34, and 40. With respect to Turing’s body of work, the treatment in Parts II–VI is broadly chronological. We have attempted to be comprehensive with respect to all the important aspects of Turing’s achievements, and the book can be read cover to cover, or the chapters can be tackled individually if desired. There are cross-references between chapters where appropriate, and some chapters will inevitably overlap. -/- We hope that you enjoy this volume as part of your library and that you will dip into it whenever you wish to enter the multifaceted world of Alan Turing. (shrink)

I. EXECUTIVE SUMMARY The MRCT Center Post-trial Responsibilities: Continued Access to an Investigational Medicine Framework outlines a case-based, principled, stakeholder approach to evaluate and guide ethical responsibilities to provide continued access to an investigational medicine at the conclusion of a patient’s participation in a clinical trial. The Post-trial Responsibilities (PTR) Framework includes this Guidance Document as well as the accompanying Toolkit. A 41-member international multi-stakeholder Workgroup convened by the Multi-Regional Clinical Trials Center of Brigham and Women’s Hospital and Harvard University (...) (MRCT Center) developed this Guidance and Toolkit. Project Motivation A number of international organizations have discussed the responsibilities stakeholders have to provide continued access to investigational medicines. The World Medical Association, for example, addressed post-trial access to medicines in Paragraph 34 of the Declaration of Helsinki (WMA, 2013): “In advance of a clinical trial, sponsors, researchers and host country governments should make provisions for post-trial access for all participants who still need an intervention identified as beneficial in the trial. This information must also be disclosed to participants during the informed consent process.” This paragraph and other international guidance documents converge on several consensus points: • Post-trial access (hereafter referred to as “continued access” in this Framework [for terminology clarification – see definitions]) is the responsibility of sponsors, researchers, and host country governments; • The plan for continued access should be determined before the trial begins, and before any individual gives their informed consent; • The protocol should delineate continued access plans; and • The plan should be transparent to potential participants and explained during the informed consent process. -/- However, there is no guidance on how to fulfill these responsibilities (i.e., linking specific responsibilities with specific stakeholders, conditions, and duration). To fill this gap, the MRCT Center convened a working group in September of 2014 to develop a framework to guide stakeholders with identified responsibilities. This resultant Framework sets forth applicable principles, approaches, recommendations and ethical rationales for PTR regarding continued access to investigational medicines for research participants. (shrink)

Epistemic contextualists think that the truth-conditions of ‘knowledge’ ascriptions depend in part on the context in which they are uttered. But what features of context play a role in determining truth-conditions? The idea that the making salient of error possibilities is a central part of the story has often been attributed to contextualists, and a number of contextualists seem to endorse it (see Cohen (Philos Perspect, 13:57–89, 1999) and Hawthorne, (Knowledge and lotteries, Oxford University Press, Oxford, 2004)). In this paper (...) I argue that the focus on salience relations is a mistake. On the view I defend, the relevant features of context are facts about what error-possibilities and alternatives those in the context have a reason to consider, not facts about what error-possibilities and alternatives those in the context actually consider. As I will argue, this view has certain advantages over the standard view. (shrink)

Gender classifications often are controversial. These controversies typically focus on whether gender classifications align with facts about gender kind membership: Could someone really be nonbinary? Is Chris Mosier really a man? I think this is a bad approach. Consider the possibility of ontological oppression, which arises when social kinds operating in a context unjustly constrain the behaviors, concepts, or affect of certain groups. Gender kinds operating in dominant contexts, I argue, oppress trans and nonbinary persons in this way: they marginalize (...) trans men and women, and exclude nonbinary persons. As a result, facts about membership in dominant gender kinds should not settle gender classification practices. (shrink)

Ordinary discourse is filled with discussions about ‘sexual orientation’. This discourse might suggest a common understanding of what sexual orientation is. But even a cursory search turns up vastly differing, conflicting, and sometimes ethically troubling characterizations of sexual orientation. The conceptual jumble surrounding sexual orientation suggests that the topic is overripe for philosophical exploration. This paper lays the groundwork for such an exploration. In it, I offer an account of sexual orientation – called ‘Bidimensional Dispositionalism’ – according to which sexual (...) orientation concerns what sex[es] and gender[s] of persons one is disposed to sexually engage, and makes no reference to one’s own sex and gender. (shrink)

Most discussions of racial fetish center on the question of whether it is caused by negative racial stereotypes. In this paper I adopt a different strategy, one that begins with the experiences of those targeted by racial fetish rather than those who possess it; that is, I shift focus away from the origins of racial fetishes to their effects as a social phenomenon in a racially stratified world. I examine the case of preferences for Asian women, also known as ‘yellow (...) fever’, to argue against the claim that racial fetishes are unobjectionable if they are merely based on personal or aesthetic preference rather than racial stereotypes. I contend that even if this were so, yellow fever would still be morally objectionable because of the disproportionate psychological burdens it places on Asian and Asian-American women, along with the role it plays in a pernicious system of racial social meanings. (shrink)

Alex Byrne’s article, “Are Women Adult Human Females?”, asks a question that Byrne treats as nearly rhetorical. Byrne’s answer is, ‘clearly, yes’. Moreover, Byrne claims, 'woman' is a biological category that does not admit of any interpretation as (also) a social category. It is important to respond to Byrne’s argument, but mostly because it is paradigmatic of a wider phenomenon. The slogan “women are adult human females” is a political slogan championed by anti-trans activists, appearing on billboards, pamphlets, and anti-trans (...) online forums. In this paper, I respond to Byrne’s argument, revealing significant problems with its background assumptions, content, and methodology. (shrink)