What is it that we are doing when we make ethical claims and judgments, such as the claim that we morally ought to assist refugees? This dissertation introduces and defends a novel theory of ethical thought and discourse. I begin by identifying the surface features of ethical thought and discourse to be explained, including the realist and cognitivist (i.e. belief-like) appearance of ethical judgments, and the apparent close connection between making a sincere ethical judgment and being motivated to act on (...) it. I examine prominent attempts to explain these features, with a focus on recent ‘hybrid’ theories combining elements of expressivism and cognitivism. Despite their initial promise, I argue that extant hybrid theories are nevertheless committed to problematic semantic, metasemantic, or pragmatic assumptions. I then discuss what I take to be the strongest existing option, ethical neo-expressivism (Bar-On and Chrisman, 2009; Bar-On, Chrisman, and Sias, 2014), and develop it into an explicitly hybrid theory proposing that ethical judgments incorporate both motivationally-charged affective states and moral beliefs. I then supplement this account with a theory of the proper function (following Millikan, 1984) of ethical claims and judgments, arguing that they function simultaneously to track the morally salient features of social situations, and to coordinate our behavior around these features. Finally, I defend one of the cognitivist commitments of the theory – namely, that objective moral knowledge is possible – by applying recent work on the epistemology of fundamental or ‘core’ intellectual commitments (Lynch, 2012; Pritchard, 2016) to the moral realm. (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)

This chapter focuses on the psychological mechanisms behind the construction of preference, especially the actual processes used by humans when they make decisions in their everyday lives or in business situations. The chapter uses cognitive psychological techniques to break down these processes and set them in their social context. When attributes are compatible with the response scale, they are assigned greater weight because they are most easily mapped onto the response. For instance, when subjects are asked to set a price (...) for a gamble this task is compatible with the information about the gamble payoff, which is also expressed in monetary values (e.g., dollars). Conversely, when the task requires a choice the payoff information is not easily mapped onto the response anymore and loses some of its salience. In fact, Slovic, Griffin, and Tversky (1990) could show that using non-monetary outcomes attenuates preference reversals when no compatibility between the pricing task and the outcome attribute was possible. An assumption of the compatibility effect is that response modes compatible with specific characteristics of the options (e.g., payoffs) draw attention to them. One of the main themes that has emerged from behavioral decision research during the past decades is the view that people's preferences are often constructed—not merely revealed—in the process of elicitation (see e.g. Slovic). This conception is derived in part from studies demonstrating that normatively equivalent methods of elicitation often give rise to systematically different responses. These "preference reversals" violate the principle of procedure invariance fundamental to theories of rational choice and raise difficult questions about the nature of human values. If different elicitation procedures produce different orderings of options, how can preferences be defined and in what sense do they exist? Describing and explaining such failures of invariance will require choice models of far greater complexity than the traditional models -/- . (shrink)

Did Donald Davidson agree with G.E.M. Anscombe that action requires a distinctive form of agential awareness? The answer is No, at least according to the standard interpretation of Davidson’s account of action. A careful study of Davidson’s early writings, however, reveals a much more subtle conception of the role of agential belief in action. While the role of the general belief in Davidson’s theory is familiar and has been much discussed, virtually no attention has been paid to the singular belief. (...) This essay makes a start on remedying this neglect. I begin, in section 1, by examining Davidson’s claim that for a desire or belief to rationalize and cause an action it must have a suitable generality. It must, he says, be ‘logically independent’ of the action itself. While he was clear about this requirement in the case of the desire that forms part of a person’s primary reason, I show in section 2 that his early treatment of belief confuses general and singular beliefs. This confusion reflects his failure clearly to distinguish the two roles belief can play in his account of action: as rationalizing cause and as agential awareness. Somewhat surprisingly, though, after he carefully drew the distinction and announced that intentional action requires practical knowledge, he pretty much ignored it. This may explain why some have assumed that Davidson parted ways with Anscombe on this. But a careful study of their writings shows that in fact they held remarkably similar views on the nature and need for practical knowledge. (shrink)

Geometry defines entities that can be physically realized in space, and our knowledge of abstract geometry may therefore stem from our representations of the physical world. Here, we focus on Euclidean geometry, the geometry historically regarded as “natural”. We examine whether humans possess representations describing visual forms in the same way as Euclidean geometry – i.e., in terms of their shape and size. One hundred and twelve participants from the U.S. (age 3–34 years), and 25 participants from the Amazon (age (...) 5–67 years) were asked to locate geometric deviants in panels of 6 forms of variable orientation. Participants of all ages and from both cultures detected deviant forms defined in terms of shape or size, while only U.S. adults drew distinctions between mirror images (i.e. forms differing in “sense”). Moreover, irrelevant variations of sense did not disrupt the detection of a shape or size deviant, while irrelevant variations of shape or size did. At all ages and in both cultures, participants thus retained the same properties as Euclidean geometry in their analysis of visual forms, even in the absence of formal instruction in geometry. These findings show that representations of planar visual forms provide core intuitions on which humans’ knowledge in Euclidean geometry could possibly be grounded. (shrink)

This is a defence of externalism about knowledge and also about justification. In this paper, I argue that an important virtue of externalism about these notions is that externalism about justification helps to explain the value of (i.e., importance of) knowledge. I also develop and expand upon some of my earlier arguments for externalism that drew upon what's now known as 'morally loaded cases'. The virtue of externalism is that it's the only view that can both allow for certain (...) kinds of categorical normative requirements while also vindicating the idea that we ought to be guided by the beliefs that we ought to have. (Internalists either have to deny that we ought to be guided by the beliefs that we ought to have (which isn't very internalist!) or, failing that, revise our views about the existence of certain kinds of categorical requirements and tell us that we ought to be guided by our beliefs to do evil things (which isn't very nice!).). (shrink)

The set of symbols of success is a set of cultural determinants of activity and their functioning is connected with the fundamental functions of culture as a system of historically developing supra-biological programs of life. The relevance of considering the symbolization of success in modern cinema is due to several factors. First, according to the majority of art historians and film theorists, cinema remains the leading, most widespread form of art throughout the 20th and 21st centuries. If we understand art (...) as a figurative comprehension of reality, its process and result, which is expressed in works, then the symbolization of success in cinema can be considered one of the most common practices for representing the determinants of activity through a figurative comprehension of reality. An analysis of this process in modern cinematography reveals the mechanisms of functioning of one of the elements of the totality of joint life programs as a segment of modern culture, limited by the boundaries of film communication. Secondly, the development of cinematography largely determines the fundamental changes in the culture of the 20th century. and there is no reason to believe that its influence is diminishing in recent times. Consequently, modern cinema remains one of the most important areas of cultural life, the study of which allows expanding scientific understanding of the patterns of changes taking place in culture. Thirdly, the development of information and communication technologies at the end of the 20th century. led to the fact that the value complexes of traditional cultures of different peoples of the world and expansive global neoplasms of a supranational nature (mass, elite, corporate, fandom, etc.) are simultaneously transmitted into the space of personal culture. Cinema in the new conditions only strengthened its position as the leading relay of value complexes. The special socio-forming qualities of cinema were noted both by its pioneers (L. Delluk, A. Dovzhenko, Ch. Chaplin, S. Eisenstein, etc.), scientists (B. Balash, V. A. Gottwald, E. M. Samuylenko, etc.) , and the ideologists of cultural revolutions at the beginning of the 20th century. G. Turner, in particular, drew attention to the fact that “to achieve control over the everyday representation of the world for a nation means to acquire strong power over the representation of individuals about themselves and about each other”, referring to the threat to the integrity and coherence of an individual’s understanding of the world under the pressure of foreign cultural domination over film communication. In this regard, the search for ways to relevantly measure the trends in the development of modern culture by marking in cinema the cultural determinants of activity, which are the symbols of success, seems to be an urgent theoretical and scientific-practical task, the solution of which expands the predictive potential of culture and its projective possibilities. (shrink)

Medieval and early modern Jewish philosophers developed their thinking in conversation with various bodies of literature. The influence of ancient Greek – primarily Aristotle (and pseudo-Aristotle) – and Arabic sources was fundamental for the very constitution of medieval Jewish philosophical discourse. Toward the late Middle Ages Jewish philosophers also established a critical dialogue with Christian scholastics. Next to these philosophical corpora, Jewish philosophers drew significantly upon Rabbinic sources (Talmud and the numerous Midrashim) and the Hebrew Bible. In order to (...) clarify the unique as well as shared elements in the thought of medieval Jewish philosophers, we will begin this chapter with a brief study of some early Rabbinic sources on the purpose of the world, i.e., why it came to be and why it is sustained in existence. In the second part of this chapter, we will study Maimonides’ critique of the veracity and usefulness of the belief in (anthropocentric) teleology, and the critical reception of his views by later philosophers. The third part will address discussions of divine teleology in Kabbalistic literature. Our exposition will concentrate mostly on a specific early-eighteenth-century text that is one of the most lucid and rigorous presentations of Lurianic Kabbalah. The fourth and final section will elucidate Spinoza’s critique of teleology, its precise target and scope, and its debt to earlier sources discussed in this chapter. (shrink)

Space exploration and the search for a better understanding of life have never been entirely separate from one another. This is not simply a matter of policy, a decision by political administrations to combine the two. Rather, it is a matter of the ways in which both draw upon the same scientific culture and upon overlapping societal influences. Some of the latter are the political influences of particular times and particular places, others are of a far broader nature. Progress in (...) one field has tended to be combined with advances in the other. It is a familiar point that, in the very year that NASA was founded, i.e. 1958, the American molecular biologist Joshua Lederberg won a Nobel Prize for his discovery that bacteria can exchange genetic material (a process now known as ‘bacterial conjugation’). This, in turn, was only six years after the classicMiller-Urey experiment to replicate the production of some of the chemical precursors of life. And the Miller-Urey experiment, in turn, overlapped in time with the work of Watson, Crick and Rosalind Franklin in England, on the structure of DNA. Major breakthroughs came in both fields (activity in space and research into life) within the same time-frame, and drew upon at least some of the same background influences and interests. When Lederberg went on to work with NASA on the early programs to look for life on Mars, the progression was, in an everyday sense, natural. Interest in space and interest in life went together. They have always tended to do so. (shrink)

This publication is the translation of the first fragment of F. W. J Schelling's Presentation of Philosophical Empiricism accompanied by the analytical translator's preface. In his treatise, Schelling assesses the history of modern philosophy. Namely, he treats it as history of experiments, the goal of which was in the search for the primary fact in the world. In Schelling's opinion, this fact is in the growing over-weight of the subjective over the objective. Only his philosophy of nature was able to (...) find this fact. However, it is not genuine fact but only pure fact, because it does not content in itself any ground for the over-weighting of the subjective over the objective. For resolve this problem, Schelling starts to use the concepts formed by Ancient philosophers, namely by Pythagoras and Plato. The concepts of the limitless and the limit are belonging to the series of the mentioned concepts. Accordantly, Schelling associates the notion of the objective with the one of the limitless being and the notion of the subjective with the one of the limit or limiting instance. His inquiry into the correlation between the limitless being and the limit, i.e. between the objective and the subjective leads him to the declaration of the existence of the free efficient cause, which determinates their interplay and the rise of that-what-should-be from that-what-should-not-be. Since the limitless is the objective and the limit is the subjective in accordance with Schelling, such efficient cause is also the cause of the progressive over-weighting of the subjective over the objective as well. It can explain the fact, which the Schelling's philosophy of nature has only found but not explained. The in his preface, the translator puts the question of the possibility as well as of a relevance of the Schelling's late philosophy to the phenomenological thought. In this context, he emphasizes few moments, by which the later Schelling' philosophy could be of interests for phenomenologists, namely the following ones: the concept of philosophical empiricism itself, the Schelling's division between the pure fact and the genuine fact, his treatment of history of philosophy as history of experiments. Moreover, he speaks about main difficulties connected with the translation of Schelling's text into Russian and gives a German-Russian glossary for utility of Russian readers. The translator gives also the commentaries by Arthur Drews, who reedited the Schelling's treatise in 1902, in their Russian translation. (shrink)

The term “Complex Systems Biology” was introduced a few years ago [Kaneko, 2006] and, although not yet of widespread use, it seems particularly well suited to indicate an approach to biology which is well rooted in complex systems science. Although broad generalizations are always dangerous, it is safe to state that mainstream biology has been largely dominated by a gene-centric view in the last decades, due to the success of molecular biology. So the one gene - one trait approch, which (...) has often proved to be effective, has been extended to cover even complex traits. This simplifying view has been appropriately criticized, and the movement called systems biology has taken off. Systems biology [Noble, 2006] emphasizes the presence of several feedback loops in biological systems, which severely limit the range of validity of explanations based upon linear causal chains (e.g. gene → behaviour). Mathematical modelling is one the favourite tools of systems biologists to analyze the possible effects of competing negative and positive feedback loops which can be observed at several levels (from molecules to organelles, cells, tissues, organs, organisms, ecosystems). Systems biology is by now a well-established field, as it can be inferred by the rapid growth in number of conferences and journals devoted to it, as well as by the existence of several grants and funded projects.Systems biology is mainly focused upon the description of specific biological items, like for example specific organisms, or specific organs in a class of animals, or specific genetic-metabolic circuits. It therefore leaves open the issue of the search for general principles of biological organization, which apply to all living beings or to at least to broad classes. We know indeed that there are some principles of this kind, biological evolution being the most famous one. The theory of cellular organization also qualifies as a general principle. But the main focus of biological research has been that of studying specific cases, with some reluctance to accept (and perhaps a limited interest for) broad generalizations. This may however change, and this is indeed the challenge of complex systems biology: looking for general principles in biological systems, in the spirit of complex systems science which searches for similar features and behaviours in various kinds of systems. The hope to find such general principles appears well founded, and I will show in Section 2 that there are indeed data which provide support to this claim. Besides data, there are also general ideas and models concerning the way in which biological systems work. The strategy, in this case, is that of introducing simplified models of biological organisms or processes, and to look for their generic properties: this term, borrowed from statistical physics, is used for those properties which are shared by a wide class of systems. In order to model these properties, the most effective approach has been so far that of using ensembles of systems, where each member can be different from another one, and to look for those properties which are widespread. This approach was introduced many years ago [Kauffman, 1971] in modelling gene regulatory networks. At that time one had very few information about the way in which the expression of a given gene affects that of other genes, apart from the fact that this influence is real and can be studied in few selected cases (like e.g. the lactose metabolism in E. coli). Today, after many years of triumphs of molecular biology, much more has been discovered, however the possibility of describing a complete map of gene-gene interactions in a moderately complex organism is still out of reach. Therefore the goal of fully describing a network of interacting genes in a real organism could not be (and still cannot be) achieved. But a different approach has proven very fruitful, that of asking what are the typical properties of such a set of interacting genes. Making some plausible hypotheses and introducing some simplifying assumptions, Kauffman was able to address some important problems. In particular, he drew attention to the fact that a dynamical system of interacting genes displays selforganizing properties which explain some key aspects of life, most notably the existence of a limited number of cellular types in every multicellular organism (these numbers are of the order of a few hundreds, while the number of theoretically possible types, absent interactions, would be much much larger than the number of protons in the universe). In section 3 I will describe the ensemble based approach in the context of gene regulatory networks, and I will show that it can describe some important experimental data. Finally, in section 4 I will discuss some methodological aspects. (shrink)

Since 2023, the UK government's response to the “migrant crisis” has revolved around two controversial flagship policies: the deportation of asylum seekers to Rwanda, and the detention of migrants aboard a giant barge. In this short article, I examine the colonial and gendered dimensions of the two policies, finding them to be examples of the coloniality of gender. What this indicates, I suggest, is that the purpose of these policies is not merely to deter potential migrants—particularly LGBTQIA+ migrants—but also to (...) create a political narrative that allows the Conservative Party to garner right-wing votes by participating in high-profile culture wars; namely, the debate over transgender rights and the debate over how the UK should reckon with its imperial past. (shrink)

Many have taken Sellars’s critique of empiricism in “Empiricism and the Philosophy of Mind” (EPM) to be aimed at his teacher C. I. Lewis. But if so, why do the famous arguments of its opening sections carry so little force against Lewis’s views? Understandably, some respond by denying that Lewis’s epistemology is among the positions targeted by Sellars. But this is incorrect. Indeed, Sellars had earlier offered more trenchant (if already familiar) critiques of Lewis’s epistemology. What is original about EPM (...) is that it criticizes empiricist positions like Lewis’s not because of their foundationalism, but because of their psychologism about meaning. Since psychologism turns out to be unacceptable by Lewis’s own lights, EPM has a compelling (if implicit) critique of Lewis to offer after all, one that strikes at the heart of his philosophical system. (shrink)

Charles Sanders Peirce has commonly been interpreted as a proponent of an epistemic theory of truth. Such a theory has the apparent advantage of directly undercutting radical skepticism, but the disadvantage of implausibly entailing that there are no truths concerning irretrievably lost facts. Recently Andrew Howat has defended Peirce’s epistemic constraint on truth by recasting Peirce’s claim that all truths would be believed following sufficient inquiry, not as constitutive of truth, but as a Wittgensteinian hinge proposition. I begin with a (...) twofold historical reply to Howat: first, Peirce can at least plausibly be read as claiming that the claim in question is analytic of the concept <truth>; and second, while Peirce did think we must accept without evidence the further claim that there are any truths (so characterized), he regarded this further claim not as a Wittgensteinian hinge but as a reasonable hope. I then substantively defend the latter Peircean proposal, arguing that hopes, as against beliefs, are chiefly warranted pragmatically, and so can be warranted even to a sufficient level to render them properly action-guiding in cases where belief in the same proposition would remain unjustified. I conclude by suggesting, first, that this proposal is superior to Wittgenstein’s own epistemology in evading psychologism, and second, that it attractively vindicates the reasonableness of inquiry on Peircean grounds that don’t require an appeal to an implausible epistemic theory of truth. (shrink)

In this article, I expound and defend an interpretation of Sellars as a metaethical quasi-realist. Sellars analyzes moral discourse in non-cognitivist terms: in particular, he analyzes “ought”-statements as expressions of collective intentions deriving from a collective commitment to provide for the general welfare. But he also endorses a functional-role theory of meaning, on which a statement’s meaning is grounded in its being governed by semantical rules concerning language entry, intra-linguistic, and language departure transitions, and a theory of truth as correct (...) assertibility relative to such semantical rules. On these non-representationalist theories, even though moral statements are expressions of intentions and not fundamentally descriptive, they nevertheless count as assertorically meaningful, and some count as positively true. I further argue that this interpretation is capable not only of explaining Sellars’ explicitly metaethical writings, but also of unifying his scientific realism with his commitment to the ineliminable and indispensable role of the language of intentions: if this linguistic framework does not play an explanatory role, but only an expressive role, this explains both why Sellars’ commitment to it does not contravene his naturalism, as well as why, given the necessity of such language for our practical engagement with the world, the scientific image of humans in the world will only be completed once such language supplements it to enable us to relate practically to it. (shrink)

Sellars was an inferentialist about meaning. He thus effectively accorded modality a categorial function, maintaining that any meaningful assertion involves implicit commitment to rules of material inference, which modal propositions explicitly endorse. But Sellars was also a modal anti-realist, construing modality as “entirely immanent to thought” (LRB §40), not present in the world an sich. These two commitments, Klemick argues, render it impossible in principle for us to describe the world an sich adequately, undermining Sellars’ scientific realism, on which, at (...) the “ideal outcome of scientific inquiry,” “the gulf between appearances and things-in-themselves [... can] be bridged” (SM II §51). Sellars’ attempt to ground his modal anti-realism in an ideal “pure description of the world” (CDCM §79) cannot succeed, given modality’s categorial function. Further, his subsequent deployment of picturing as a naturalistic criterion of ontological commitment founders on an analogue of the Kantian problem of noumenal affection: the descriptions of picturing relations that render this proposal intelligible are emptied of content by the denial that the in-itself is modally characterized. Sellars’ worthy aim of preserving the world’s independence of our conceptual activity, Klemick concludes, doesn’t require denying that it exhibits modal relations isomorphic to the semantic relations within our conceptual scheme. (shrink)

While C. I. Lewis was traditionally interpreted as an epistemological foundationalist throughout his major works, virtually every recent treatment of Lewis's epistemology dissents. But the traditional interpretation is correct: Lewis believed that apprehensions of "the given" are certain independently of support from, and constitute the ultimate warrant for, objective empirical beliefs. This interpretation proves surprisingly capable of accommodating apparently contrary textual evidence. The non-foundationalist reading, by contrast, simply cannot explain Lewis's explicit opposition to coherentism and his insistence that only apprehensions (...) of the given enable us to answer the regress problem -- and so vindicate the possibility of empirical justification. (shrink)

Pragmatist responses to skepticism about empirical justification have mostly been underwhelming, either presupposing implausible theses like relativism or anti-realism, or else showing our basic empirical beliefs to be merely psychologically inevitable rather than rationally warranted. In this paper I defend a better one: a modified version of an argument by Wilfrid Sellars that we are pragmatically warranted in accepting that our perceptual beliefs are likely to be true, since their likely truth is necessary for the satisfaction of our goal of (...) effective agency. On the version of the argument I defend, the great good for human life of control over our empirical circumstances renders our goal of effective agency reasonable. But only if our perceptual beliefs are likely to be true—and only if we accept that this is so, assuming it as a premise for inference and a guide for action—will the success of our actions be due to our effective agency, not mere luck. Since we’re warranted in taking the necessary means to our reasonable ends, we’re warranted in accepting that our perceptual beliefs are generally justified, and so that skepticism about empirical justification is false. (shrink)

Why is it that some instances of disagreement appear to be so intractable? And what is the appropriate way to handle such disagreements, especially concerning matters about which there are important practical and political needs for us to come to a consensus? In this paper, I consider an explanation of the apparent intractability of deep disagreement offered by hinge epistemology. According to this explanation, at least some deep disagreements are rationally unresolvable because they concern ‘hinge’ commitments that are unresponsive to (...) rational considerations. This explanation, if correct, seems to have troubling implications for how we should respond to deep disagreement. If my position on a topic is not responsive to rational considerations, then what choice have I but to dogmatically hold to that position, and simply dismiss the views of those with whom I disagree? I address this problem by identifying an attitude of intellectual humility that is appropriate to have towards one's hinge commitments, and suggest that this attitude provides the basis for a non-rational, constructive way to resolve deep disagreement. (shrink)

In “The Fixation of Belief,” Peirce apparently accepts the causal claim that real physical objects cause us to reach an indefeasible “final opinion” concerning them. In “How to Make Our Ideas Clear,” he apparently accepts the constitutive claim that for physical objects to be real just is for them to be represented in that opinion. These claims initially seem inconsistent, since causal claims are explanatory and since equivalent claims cannot explain one another. Contrary to prominent suggestions that Peirce rejected the (...) constitutive claim, however, he actually accepted both, reconciling them via a Humean denial that causal claims are genuinely explanatory. (shrink)

I take up two questions raised by Luz Christopher Seiberth's meticulous reconstruction of Wilfrid Sellars's theory of intentionality. The first is whether we should regard Sellars as a transcendental phenomenalist in the most interesting sense of the term: as denying that even an ideally adequate conceptual structure would enable us to represent worldly objects as they are in themselves. I agree with Seiberth that the answer is probably yes, but I suggest that this is due not to Sellars's rejection of (...) the Myth of the Given or appeal to image-models (as Seiberth maintains), but to his view of modality as categorial but as absent from the world an sich. The second is whether, as Richard Rorty complained, Sellars's appeal to picturing lands his theory of intentionality in intractable skepticism. Pace Seiberth, I argue that the transcendental role of picturing does not mitigate this problem, and I suggest that Sellars's most fruitful resource for doing so is not his semantic externalism, but his purely pragmatic response to skepticism. (shrink)

The option of being ‘spiritual but not religious’ deserves much more philosophical attention. That is the aim here, taking the work of Robert Solomon as a starting point, with focus on the particular issues around viewing life as gift. This requires analysis of ‘existential gratitude’ to show that there can be gratitude for things without gratitude to someone for providing things, and also closer attention to the role that metaphor plays in cognition. I consider two main concerns with gift and (...) gratitude thinking, that the nonreligious justification is too instrumentalist in its approach and that viewing life as gift, whether in a religious or nonreligious way, is simply too optimistic. (shrink)

The focus of this article is the "good-will theory", which explains the effect humans can have on the safety of AI, along with how it is in the best interest of a superintelligent AI to work alongside humans and not overpower them. Future papers dealing with the good-will theory will be published, but discuss different talking points in regards to possible or real objections to the theory.

Russell’s rejection in 1898 of the doctrine of internal relations — the view that all relations are grounded in the intrinsic properties of the terms related — was a decisive part of his break with Hegelianism and opened the way for his turn to analytic philosophy. Before rejecting it, Russell had given the doctrine little thought, though it played an essential role in the most intractable of the problems facing his attempt to construct a Hegelian dialectic of the sciences. I (...) argue that it was Russell’s early reading of Leibniz, in preparation for his lectures on Leibniz given at Cambridge in 1899, that most probably alerted him to the role the doctrine was playing in his own philosophy. Leibniz defended a similar doctrine and extricated it from difficulties like those faced by Russell by means of devices that were not open to Russell. Russell would have come across these views of Leibniz in writings by Leibniz that he read in the summer of 1898, just before he rejected the doctrine of internal relations. (shrink)

Alan Hodgkin and Andrew Huxley used abductive reasoning to draw conclusions about the ionic basis of the action potential. Here we build on that initial proposal. First, we propose that Hodgkin and Huxley’s constitutive abductive reasoning has four features. Second, we argue that Hodgkin and Huxley are not alone in giving such arguments. Tolman, 1948, and Baumgartner, 1960, also gave such arguments. The implication is that such arguments are common enough in science that philosophers of science should pay more attention (...) to them. Third, we propose that constitutive abduction describes a method that scientists use to confirm constitutive hypotheses that is an alternative to the mutual manipulability approach that is familiar in the New Mechanist literature. (shrink)

Proclus argues that place (topos) is a body of light, identified as the luminous vehicle of the soul, which mediates between soul and body and facilitates motion. Simplicius (in Phys. 611,10–13) suggests that this theory is original to Proclus, and unique in describing light as a body. This paper focuses on the function of this theory as a bridge between Proclus’ physics and metaphysics, allowing the Aristotelian physical notion of “natural place” to serve as a mechanism for the descent and (...) ascent of the soul. (shrink)

There seems to be confusion and disagreement among scholars about the meaning of interpersonal forgiveness. In this essay we shall venture to clarify the meaning of forgiveness by examining various literary works. In particular, we shall discuss instances of forgiveness from Homer’s The Iliad, Euripides’ Hippolytus, and Aristotle’s Nicomachean Ethics and we shall focus on the changes that the concept of forgiveness has gone through throughout the centuries, in the hope of being able to understand, and therefore, of being able (...) to use more accurately, contemporary notions of forgiveness. We shall also explore the relationship between forgiveness and concepts that are closely associated with it, such as anger/resentment, hurt, clemency, desert/merit, excuse, etc. (shrink)

This paper explores how hinge epistemology might fruitfully be applied not only to the problem of radical skepticism, but also to certain domain specific skepticisms, and in particular, moral skepticism. The paper explains the idea of a domain specific skepticism, and how domain specific skepticisms contrast with radical skepticism. I argue that a domain specific skeptical problem can be resolved in just the same way as radical skepticism, if there are hinge commitments within that domain. I then suggest that there (...) are hinge commitments in the moral domain, and use this to address a moral skeptical problem due to our apparent inability to know moral nihilism to be false. (shrink)

The article delves into the mystery that underlies the true nature of reality..Do we view reality as it is or is reality an illusion in the sense that it's a product of our senses rather than a fundamental part of the universe? These are some of the questions that have puzzled great thinkers for millennia.. The true nature of reality seems to be utterly elusive just as Brian Greene said "sometimes nature guards her secrets by the unbreakable grip of physical (...) law, sometimes the true nature of reality beckons from just beyond the horizon". (shrink)

The proliferation of work by autistic writers continues apace, defying a long and multidisciplinary tradition of constructing autistic people as lacking the capacity for narration. To study neurodivergent literature, then, is to witness the refusal of these exclusionary narrative conventions, and to register the ideological presuppositions that underpin pathologization. In this article, I engage with recent insights from Neurodiversity Studies to explore the connections between narrative neuronormativity and other discourses of oppression, especially those that have generated racialized, gendered, and colonial (...) narratives of desubjectification. Focusing on the neuroqueer movement—an emergent practice of disidentification that refuses the interpellations of neuronormativity, ableism, heteronormativity, and cisnormativity—I discuss the concept of allism, arguing that this satirical critique of pathologization harbors a deconstructive force that denaturalizes the dialectic of recognition. Pursuing the discursive context and theoretical implications of this critique, I provide a short genealogy of narrative neuronormativity, connecting the operation of the dialectic in the early novel to the clinical texts of child psychology. To demonstrate the neuroqueer subversion of this tradition, I then read An Unkindness of Ghosts, by Rivers Solomon, a text that stages a disidentification with storytelling. Protagonist Aster’s neuroqueer refusal indexes the concomitance of the construction of Blackness as an ontological foil for whiteness and the construction of autism as a standard of disordered sociality that neuronorms can be measured against. My reading of Unkindness suggests that the extant techniques of literary narratorship are political instruments that will, unless repurposed, continue to disseminate these dispossessive dialectics. (shrink)

Williamson's influential anti-luminosity argument aims to show that our own mental states are not “luminous,” and that we are thus “cognitively homeless.” Among other things, this argument represents a significant challenge to the idea that we enjoy basic self-knowledge of our own occurrent mental states. In this paper, I summarize Williamson's anti-luminosity argument, and discuss the role that the notion of “epistemic basis” plays in it. I argue that the anti-luminosity argument relies upon a particular version of the basis-relative safety (...) condition on knowledge. This commitment is significant because basic self-knowledge seemingly lacks any kind of distinct epistemic basis, such as inference, observation, testimony, etc., despite representing a genuine kind of knowledge of contingent matters of fact. I consider a disjunctivist account, according to which true basic self-beliefs indeed lack an epistemic basis in any kind of epistemic method, yet are still epistemically grounded in the mental states they concern. I argue that this account of self-knowledge is compatible with standard understandings of the basis relative safety condition on knowledge, but rejects the particular version required by the anti-luminosity argument. (shrink)

Some New Mechanists have proposed that claims of compositional relations are justified by combining the results of top-down and bottom-up interlevel interventions. But what do scientists do when they can perform, say, a cellular intervention, but not a subcellular detection? In such cases, paired interlevel interventions are unavailable. We propose that scientists use abduction and we illustrate its use through a case study of the ionic theory of resting and action potentials.

The claim has often been made that passing the Turing Test would not be sufficient to prove that a computer program was intelligent because a trivial program could do it, namely, the “Humongous-Table (HT) Program”, which simply looks up in a table what to say next. This claim is examined in detail. Three ground rules are argued for: (1) That the HT program must be exhaustive, and not be based on some vaguely imagined set of tricks. (2) That the HT (...) program must not be created by some set of sentient beings enacting responses to all possible inputs. (3) That in the current state of cognitive science it must be an open possibility that a computational model of the human mind will be developed that accounts for at least its nonphenomenological properties. Given ground rule 3, the HT program could simply be an “optimized” version of some computational model of a mind, created via the automatic application of program-transformation rules [thus satisfying ground rule 2]. Therefore, whatever mental states one would be willing to impute to an ordinary computational model of the human psyche one should be willing to grant to the optimized version as well. Hence no one could dismiss out of hand the possibility that the HT program was intelligent. This conclusion is important because the Humongous-Table Program Argument is the only argument ever marshalled against the sufficiency of the Turing Test, if we exclude arguments that cognitive science is simply not possible. (shrink)

Russell is often accused of having a naive ‘Fido’–Fido theory of meaning of the sort Wittgenstein attacked at the beginning of the Philosophical Investigations. In this paper I argue that he never held such a theory though I concede that, prior to 1918, he said various things that might lead a very careless reader to suppose that he had. However, in The Analysis of Mind, a book which we know Wittgenstein studied closely, Russell put forward an account of understanding an (...) utterance which clearly anticipates the use theory of meaning usually attributed to Wittgenstein. The paper concludes with some problems for understanding the use theory of meaning as presented by both Russell and, derivatively, Wittgenstein. (shrink)

There are many things—call them ‘experts’—that you should defer to in forming your opinions. The trouble is, many experts are modest: they’re less than certain that they are worthy of deference. When this happens, the standard theories of deference break down: the most popular (“Reflection”-style) principles collapse to inconsistency, while their most popular (“New-Reflection”-style) variants allow you to defer to someone while regarding them as an anti-expert. We propose a middle way: deferring to someone involves preferring to make any decision (...) using their opinions instead of your own. In a slogan, deferring opinions is deferring decisions. Generalizing the proposal of Dorst (2020a), we first formulate a new principle that shows exactly how your opinions must relate to an expert’s for this to be so. We then build off the results of Levinstein (2019) and Campbell-Moore (2020) to show that this principle is also equivalent to the constraint that you must always expect the expert’s estimates to be more accurate than your own. Finally, we characterize the conditions an expert’s opinions must meet to be worthy of deference in this sense, showing how they sit naturally between the too-strong constraints of Reflection and the too-weak constraints of New Reflection. (shrink)

The article tries to answer the questions ; what is consciousness? Why would a collection of matter be conscious? It attempts to describe a universal consciousness that is a fundamental part of building blocks of nature. It applies a counterintuitive view of consciousness in that consciousness is not a product of a brain but a fundamental part of the universe.. Panpsychism.

Zombies are hypothetical creatures identical to us in behavior and internal functionality, but lacking experience. When the concept of zombie is examined in careful detail, it is found that the attempt to keep experience out does not work. So the concept of zombie is the same as the concept of person. Because they are only trivially conceivable, zombies are in a sense inconceivable.

David Hume, a leading Scottish Enlightenment philosopher using empirical investigation, examines and explains his view on human nature, society, and morality in A Treatise of Human Nature (Treatise) and in An Enquiry Concerning the Principles of Morals (Enquiry). In Dr. Jekyll and Mr. Hyde (Jekyll and Hyde), Robert Louis Stevenson draws from the Enlightenment’s empirical explorations in the study of the individual and society, to tell a story examining human nature.

Logic is useful as a neutral formalism for expressing the contents of mental representations. It can be used to extract crisp conclusions regarding the higher-order theory of phenomenal consciousness developed in (McDermott 2001, 20007). A key aspect of conscious perceptions is their connection to the distinction between appearance and reality. Perceptions must often be corrected. To do so requires that the logic of perception be able to represent the logical structure of judgment events, that is, to include the formulas of (...) the logic as objects to be reasoned about. However, there is a limit to how finely humans can examine their own representations. Terms representing primary and secondary qualities seemed to be _locked,_ so that the numbers (or levels of neural activation) that are their essence are not directly accessible. Humans feel a need to invoke ``intrinsic,'' ``nonrelational'' properties of many secondary qualities --- their _qualia_ --- to ``explicate'' how we compare and discriminate among them, although this is not actually how the comparisons are accomplished. This model of qualia explains several things: It accounts for the difference between ``normal'' and ``introspective'' access to a perceptual module in terms of quotation. It dissolves Jackson's knowledge argument by explaining what Mary learns as a fictional but undoubtable belief structure. It makes spectrum inversion logically impossible by providing a degree of freedom between the physical structure of the brain and the representations it contains that redescribes putative cases of spectrum inversion as alternative but equivalent ways of mapping physical states to representational states. (shrink)

This paper explores two related questions in late Athenian and Alexandrian Neoplatonism. First, how can a philosopher contemplate the eternal Forms while engaging in practical agency in the world? Second, do Neoplatonists provide a consistent account of the philosopher’s progress through the ‘stages of virtue’ (βαθμοί τῶν ἀρετῶν), the conceptual structure that underpins late antique philosophical curricula and hagiography? These questions interact, I suggest, because later Platonists appeal to the stages of virtue and divine maniai (βαθμοί τῶν μανίων) to explain (...) the philosopher’s ability to alternate gracefully between contemplation and embodied agency, and even to engage in both activities at the same moment. I argue that apparently contradictory evidence for the highest stages of virtue can be reconciled satisfactorily, shedding light on two models of ethical and perceptual transformation that are consistent throughout later Neoplatonism. In the first, 'painterly' model, we alternate between a vision of the paradigmatic model and its expression in the media of place and time; in the second, 'dancerly' model, we contemplate in action all at once, like a dancer moving to the music. (shrink)

Sometimes constitutions fail. The unprecedented election of Donald Trump, a populist insurgent who lacks the prior political experience or military service of all presidents before him, is such a sharp break in American historical experience that it raises questions as to whether something is deeply amiss with the constitutional order. Constitutional failure is not uncommon. A path-breaking global study of national constitutions shows that on average, they last only nineteen years. The U.S. Constitution is an uncommon outlier and, as such, (...) is accounted by many a long-running success story. But could a bell be tolling for American constitutionalism? In this Essay, I assess the meaning of Trump’s shocking rise for the future of our constitutional order. The shock, of course, was not the election of a Republican president. There have been many Republican presidents since Lincoln, each making their own distinctive contribution to the American tradition. Yet, there are good reasons to think this time around is different. The efficacy and, perhaps, stability of our constitutional order are in question, and we should try to understand why. (shrink)

In this article, we propose the Fair Priority Model for COVID-19 vaccine distribution, and emphasize three fundamental values we believe should be considered when distributing a COVID-19 vaccine among countries: Benefiting people and limiting harm, prioritizing the disadvantaged, and equal moral concern for all individuals. The Priority Model addresses these values by focusing on mitigating three types of harms caused by COVID-19: death and permanent organ damage, indirect health consequences, such as health care system strain and stress, as well as (...) economic destruction. It proposes proceeding in three phases: the first addresses premature death, the second long-term health issues and economic harms, and the third aims to contain viral transmission fully and restore pre-pandemic activity. -/- To those who may deem an ethical framework irrelevant because of the belief that many countries will pursue "vaccine nationalism," we argue such a framework still has broad relevance. Reasonable national partiality would permit countries to focus on vaccine distribution within their borders up until the rate of transmission is below 1, at which point there would not be sufficient vaccine-preventable harm to justify retaining a vaccine. When a government reaches the limit of national partiality, it should release vaccines for other countries. -/- We also argue against two other recent proposals. Distributing a vaccine proportional to a country's population mistakenly assumes that equality requires treating differently situated countries identically. Prioritizing countries according to the number of front-line health care workers, the proportion of the population over 65, and the number of people with comorbidities within each country may exacerbate disadvantage and end up giving the vaccine in large part to wealthy nations. (shrink)

Resumo: A crise na União Europeia e os programas de austeridade subsequentes fizeram emergir uma miríade de movimentos sociais, diversos na sua natureza e nos seus propósitos. O que se pretende aferir neste artigo é a relação e a conexão existentes entre o Estado, o poder económico, a sociedade civil e os movimentos sociais neste contexto específico de crise. Procuraremos, nesta breve abordagem, explanar alguns elementos de originalidade intrínsecos aos movimentos sociais hodiernos, patentes na sua forma de participação e organização, (...) assim como aplicar estas questões teóricas relevantes ao contexto português. A parte empírica, dada a escassez de estudos de caso existentes, será apoiada no último inquérito do European Social Survey, de 2012. Analisando um conjunto de perguntas aí explícitas, podemos compreender, de forma indirecta, algumas das dinâmicas que caracterizam estes movimentos. Abstract: The crisis in the European Union and the subsequent austerity programs have unleashed a myriad of social movements, diverse in its nature and purpose. The purpose of this paper is to assess the relationship and connection between the State, economic power, civil society and social movements in this specific context of crisis. We will try, in this brief approach, to explain some elements of originality intrinsic to modern social movements, evident in their form of participation and organization, as well as to apply these theoretical questions relevant to the Portuguese context. The empirical part, given the paucity of existing case studies, will be supported in the last survey of the European Social Survey of 2012. By analyzing a set of questions explicit there, we can, indirectly, understand some of the dynamics that characterize these movements. (shrink)

Este ensaio estabelece uma comparação estética e fenomenológica entre os pensamentos de Yves-Klein e Merleau-Ponty. Se o pintor materializou as suas reflexões e concepções em obra pictórica, o fenomenólogo francês dissertou na escrita filosófica o resultado da sua reflexão. Da análise conjunta entre um e outro resulta esta fenomenologia e estética comparativa que apresenta alguns conceitos fundamentais que alimentaram essas reflexões, tais como a visibilidade, o corpo, o mundo. Assim, para além dessa comparação, este ensaio viabiliza o diálogo entre ambos. (...) Palavras-chave: Corpo. Mundo. Visibilidade. Merleau-Ponty. Yves Klein -/- Abstract:This essay establishes an aesthetic and phenomenological comparison between the thoughts of Yves-Klein and Merleau-Ponty. If the painter materialized his reflections and concepts in pictorial work, the French phenomenologist disserted in the philosophical writing the result of his reflection. From the joint analysis between one and the other, this phenomenology and comparative aesthetics results, which presents some fundamental concepts that fed these reflections such as visibility, the body, the world. Thus, in addition to this comparison, this essay enables the dialogue between both. Keywords: Body. World. Visibility. Merleau-Ponty. Yves Klein. (shrink)

Wittgenstein’s concepts shed light on the phenomenon of schizophrenia in at least three different ways: with a view to empathy, scientific explanation, or philosophical clarification. I consider two different “positive” wittgensteinian accounts―Campbell’s idea that delusions involve a mechanism of which different framework propositions are parts, Sass’ proposal that the schizophrenic patient can be described as a solipsist, and a Rhodes’ and Gipp’s account, where epistemic aspects of schizophrenia are explained as failures in the ordinary background of certainties. I argue that (...) none of them amounts to empathic-phenomenological understanding, but they provide examples of how philosophical concepts can contribute to scientific explanation, and to philosophical clarification respectively. (shrink)

This study determined the cognitive skills achievement in mathematics of elementary pre-service teachers as a basis for improving problem-solving and critical thinking which was analyzed using Piaget's seven logical operations namely: classification, seriation, logical multiplication, compensation, ratio and proportional thinking, probability thinking, and correlational thinking. This study utilized an adopted Test on Logical Operations (TLO) and descriptive research design to describe the cognitive skills achievement and to determine the affecting factors. Overall, elementary pre-service teachers performed with sufficient understanding in dealing (...) with the TLO. However, in each logical operation, students were found to have insufficient understanding of probability thinking and correlational thinking. These insufficiencies in other logical operations were attributed to their misconceptions on some mathematical terms, misinterpretation of the problems, poor comprehension skills, poor problem-solving skills, and poor performance in mathematics in general. (shrink)