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)

Mathematicians often speak of conjectures as being confirmed by evidence that falls short of proof. For their own conjectures, evidence justifies further work in looking for a proof. Those conjectures of mathematics that have long resisted proof, such as the Riemann hypothesis, have had to be considered in terms of the evidence for and against them. In recent decades, massive increases in computer power have permitted the gathering of huge amounts of numerical evidence, both for conjectures in pure mathematics and (...) for the behavior of complex applied mathematical models and statistical algorithms. Mathematics has therefore become (among other things) an experimental science (though that has not diminished the importance of proof in the traditional style). We examine how the evaluation of evidence for conjectures works in mathematical practice. We explain the (objective) Bayesian view of probability, which gives a theoretical framework for unifying evidence evaluation in science and law as well as in mathematics. Numerical evidence in mathematics is related to the problem of induction; the occurrence of straightforward inductive reasoning in the purely logical material of pure mathematics casts light on the nature of induction as well as of mathematical reasoning. (shrink)

Occasionally, in the introductory philosophy courses I teach, a student will give an interesting argument for non-belief in God. Though I have never seen this argument in print, it seems familiar. Basically, the argument goes like this. Religious belief is largely determined by geography – where you are born and raised largely determines your religious beliefs. But believing something just because of where you are born and raised is not a reliable indication of whether that belief turns out to be (...) true. So, in some sense, you are not justified in your religious beliefs. I will attempt a more rigorous reconstruction of this argument and offer an objection to it. (shrink)

In debates over life and death it is often said that one should err on the side of caution—that is, on the side of life. In light of the recent case of Terri Schiavo, it is explained how the “err-on-the-side-of-life” argument proceeds, and an objection to it is offered.

We propose capability as a universal or type intermediate between function and disposition. A capability is, broadly speaking, a disposition that is of a type whose instances can be evaluated on the basis of how well they are realized. A function, on the view we are proposing, is a capability the possession of which is the rationale for the existence of its bearer. To say for example that a water pump has the function to pump water is to say that (...) the pump exists because something was needed that would pump water. A water pump may have many capabilities, including: to be weatherproof, to run without lubricant, to be transportable, and so forth. But its function is to pump water. We focus here on capabilities possessed by humans – such as piano playing or language using – and we explore the relation between capabilities of these sorts and structures in the brain. (shrink)

We propose a definition of capability as a class intermediate between function and disposition as the latter are defined in Basic Formal Ontology (BFO). A disposition inheres in a material entity and is realized in a certain kind of process. An example is the disposition of a glass to break when struck, which is realized when it shatters. A function is a disposition which is (simply put) the rationale for the existence of its bearer. To say for example that a (...) water pump has the function to pump water is to say that the pump exists because something was needed that would pump water. Capabilities are a special sort of disposition in that that, like functions, they can be evaluated on the basis of how well they are realized. They differ from functions in that their realizations are not the rationale – not the primary reason – for the existence of their bearers. Thus, a water pump may have many capabilities, including to be weatherproof, to run without lubricant, and so forth, but only one function. All functions are capabilities on the view we defend, but not all capabilities are functions. We develop a series of axioms to distinguish capabilities formally from both dispositions and functions and provide examples of the use of ‘capability’ in a variety of domains. (shrink)

In “Toward an Ontology of Commercial Exchange” [11], we proposed human readable definitions for terms that are central to an ontology of commercial exchange. This paper furthers that project in two ways. First, the definitions have been modified to be compatible with the Common Core Ontologies (CCO). CCO is used in a wide variety of domains including the industrial and military domains. Having a commerce ontology compatible with CCO allows data about the exchange of goods relevant to those domains to (...) be tagged with compatible ontologies. Second, we propose preliminary formalizations of these definitions, with the aim of informing the creation of an ontology which can be used to assist in reasoning over businessrelated data. (shrink)

Whether or not quantum physics can account for molecular structure is a matter of considerable controversy. Three of the problems raised in this regard are the problems of molecular structure. We argue that these problems are just special cases of the measurement problem of quantum mechanics: insofar as the measurement problem is solved, the problems of molecular structure are resolved as well. In addition, we explore one consequence of our argument: that claims about the reduction or emergence of molecular structure (...) cannot be settled independently of the choice of a particular resolution to the measurement problem. Specifically, we consider how three standard putative solutions to the measurement problem inform our under- standing of a molecule in isolation, as well as of chemistry’s relation to quantum physics. (shrink)

The interventionist account of causal explanation, in the version presented by Jim Woodward, has been recently claimed capable of buttressing the widely felt—though poorly understood—hunch that high-level, relatively abstract explanations, of the sort provided by sciences like biology, psychology and economics, are in some cases explanatorily optimal. It is the aim of this paper to show that this is mistaken. Due to a lack of effective constraints on the causal variables at the heart of the interventionist causal-explanatory scheme, as presently (...) formulated it is either unable to prefer high-level explanations to low, or systematically overshoots, recommending explanations at so high of a level as to be virtually vacuous. (shrink)

Scientific realists don’t standardly discriminate between, say, biology and fundamental physics when deciding whether the evidence and explanatory power warrant the inclusion of new entities in our ontology. As such, scientific realists are committed to a lush rainforest of special science kinds (Ross, 2000). Viruses certainly inhabit this rainforest – their explanatory power is overwhelming – but viruses’ properties can be explained from the bottom up: reductive explanations involving amino acids are generally available. However, reduction has often been taken to (...) lead to a metaphysical downgrading, so how can viruses keep their place in the rainforest? In this paper, we show how the inhabitants of the rainforest can be inoculated against the eliminative threat of reduction: by demonstrating that they are emergent. According to our account, emergence involves a screening off condition as well as novelty. We go on to demonstrate that this account of emergence, which is compatible with theoretical reducibility, satisfies common intuitions concerning what should and shouldn’t count as real: viruses are emergent, as are trout and turkeys, but philosophically gerrymandered objects like trout-turkeys do not qualify. (shrink)

An Aristotelian Philosophy of Mathematics breaks the impasse between Platonist and nominalist views of mathematics. Neither a study of abstract objects nor a mere language or logic, mathematics is a science of real aspects of the world as much as biology is. For the first time, a philosophy of mathematics puts applied mathematics at the centre. Quantitative aspects of the world such as ratios of heights, and structural ones such as symmetry and continuity, are parts of the physical world and (...) are objects of mathematics. Though some mathematical structures such as infinities may be too big to be realized in fact, all of them are capable of being realized. Informed by the author's background in both philosophy and mathematics, but keeping to simple examples, the book shows how infant perception of patterns is extended by visualization and proof to the vast edifice of modern pure and applied mathematical knowledge. (shrink)

Thomas Polger has argued in favor of the mind-brain type-identity theory, the view that mental states or processes are type-identical to states of the central nervous system. Acknowledging that the type-materialist must respond to Kripke's modal anti-materialist argument, Polger insists that Kripke's argument rests on dubious assumptions concerning the identity conditions of brain states. In brief, Polger claims that one knows that x and y are non-identical when one knows the identity conditions for both x and y. Replace x and (...) y with 'brain states' and 'sensations' and it follows that one can know that brain states and sensations are non-identical only if one knows the identity conditions for brain states. But, according to Polger, we do not know the identity conditions for brain states. Hence, we should not be so confident that brains states and sensations are non-identical after all. But Polger's account is terribly flawed. Ironically, if Polger's skepticism is warranted, then Polger himself has no good reasons to be a type-materialist. But more importantly, Polger's skepticism regarding the identity conditions of brain states is deeply defective. We do, I submit, understand the identity conditions of brain states. In the end, I submit, Kripke is safe from Polger. (shrink)

It is commonly claimed that the universality of critical phenomena is explained through particular applications of the renormalization group. This article has three aims: to clarify the structure of the explanation of universality, to discuss the physics of such RG explanations, and to examine the extent to which universality is thus explained. The derivation of critical exponents proceeds via a real-space or a field-theoretic approach to the RG. Building on work by Mainwood, this article argues that these approaches ought to (...) be distinguished: while the field-theoretic approach explains universality, the real-space approach fails to provide an adequate explanation. (shrink)

Brains, unlike artificial neural nets, use symbols to summarise and reason about perceptual input. But unlike symbolic AI, they “ground” the symbols in the data: the symbols have meaning in terms of data, not just meaning imposed by the outside user. If neural nets could be made to grow their own symbols in the way that brains do, there would be a good prospect of combining neural networks and symbolic AI, in such a way as to combine the good features (...) of each. The article argues the cluster analysis provides algorithms to perform the task, and that any solution to the task must be a form of cluster analysis. (shrink)

There is a wide range of realist but non-Platonist philosophies of mathematics—naturalist or Aristotelian realisms. Held by Aristotle and Mill, they played little part in twentieth century philosophy of mathematics but have been revived recently. They assimilate mathematics to the rest of science. They hold that mathematics is the science of X, where X is some observable feature of the (physical or other non-abstract) world. Choices for X include quantity, structure, pattern, complexity, relations. The article lays out and compares these (...) options, including their accounts of what X is, the examples supporting each theory, and the reasons for identifying the science of X with (most or all of) mathematics. Some comparison of the options is undertaken, but the main aim is to display the spectrum of viable alternatives to Platonism and nominalism. It is explained how these views answer Frege’s widely accepted argument that arithmetic cannot be about real features of the physical world, and arguments that such mathematical objects as large infinities and perfect geometrical figures cannot be physically realized. (shrink)

Though there is no international government, there are many international regimes that enact binding regulations on particular matters. They include the Basel II regime in banking, IFRS in accountancy, the FIRST computer incident response system, the WHO’s system for containing global epidemics and many others. They form in effect a very powerful international public sector based on technical expertise. Unlike the public services of nation states, they are almost free of accountability to any democratically elected body or to any legal (...) system. Although by and large they have acted for good, the dangers of long-term unaccountability are illustrated by the travesties of justice perpetrated by the International Labour Organisation Administrative Tribunal. (shrink)

This paper critiques the new mechanistic explanatory program on grounds that, even when applied to the kinds of examples that it was originally designed to treat, it does not distinguish correct explanations from those that blunder. First, I offer a systematization of the explanatory account, one according to which explanations are mechanistic models that satisfy three desiderata: they must 1) represent causal relations, 2) describe the proper parts, and 3) depict the system at the right ‘level.’ Second, I argue that (...) even the most developed attempts to fulfill these desiderata fall short by failing to appropriately constrain explanatorily apt mechanistic models. -/- *This paper used to be called "The Emperor's New Mechanisms". (shrink)

Among the factors necessary for the occurrence of some event, which of these are selectively highlighted in its explanation and labeled as causes — and which are explanatorily omitted, or relegated to the status of background conditions? Following J. S. Mill, most have thought that only a pragmatic answer to this question was possible. In this paper I suggest we understand this ‘causal selection problem’ in causal-explanatory terms, and propose that explanatory trade-offs between abstraction and stability can provide a principled (...) solution to it. After sketching that solution, it is applied to a few biological examples, including to a debate concerning the ‘causal democracy’ of organismal development, with an anti-democratic (though not a gene-centric) moral. (shrink)

The universality of critical phenomena is best explained by appeal to the Renormalisation Group (RG). Batterman and Morrison, among others, have claimed that this explanation is irreducible. I argue that the RG account is reducible, but that the higher-level explanation ought not to be eliminated. I demonstrate that the key assumption on which the explanation relies – the scale invariance of critical systems – can be explained in lower-level terms; however, we should not replace the RG explanation with a bottom-up (...) account, rather we should acknowledge that the explanation appeals to dependencies which may be traced down to lower levels. (shrink)

Journal of Applied Philosophy, EarlyView.

What is it about a person's becoming an adult that makes it generally inappropriate to treat that person paternalistically any longer? The Standard View holds that a mere difference in age or stage of life cannot in itself be morally relevant, but only matters insofar as it is correlated with the development of capacities for mature practical reasoning. This paper defends the contrary view: two people can have all the same general psychological attributes and yet the mere fact that one (...) person is at the beginning of a life and another in the middle of one can justify treating the younger person more paternalistically than the older one. Recognising the moral relevance of age, moreover, is crucial if one is to accommodate both the liberal moral ideal of respect for autonomy and our demanding educational aims, given that these otherwise come into conflict with one another. (shrink)

In our daily lives, as in science and in all other domains, we encounter huge numbers of dispositions (tendencies, potentials, powers) which are realized in processes such as sneezing, sweating, shedding, melting. Among this plethora of what we can think of as ‘mere dispositions’ is a subset of dispositions in whose realizations we have an interest – a car responding well when driven on ice, a rabbit’s lungs responding well when it is chased by a wolf, and so on. We (...) call the latter ‘capabilities’ and we attempt to provide an ontological account of what capabilities are that is of sufficient generality to serve a variety of purposes, for example by providing a useful extension to ontology-based research in areas where capabilities data are being collected in siloed fashion. (shrink)

Multiple realisation prompts the question: how is it that multiple systems all exhibit the same phenomena despite their different underlying properties? In this paper I develop a framework for addressing that question and argue that multiple realisation can be reductively explained. I illustrate this position by applying the framework to a simple example – the multiple realisation of electrical conductivity. I defend my account by addressing potential objections:contra Polger and Shapiro, Batterman, and Sober, I claim that multiple realisation is commonplace, (...) that it can be reductively explained, but that it requires asui generisreductive explanatory strategy. (shrink)

Philosophers of experiment have acknowledged that experiments are often more than mere hypothesis-tests, once thought to be an experiment's exclusive calling. Drawing on examples from contemporary biology, I make an additional amendment to our understanding of experiment by examining the way that `wide' instrumentation can, for reasons of efficiency, lead scientists away from traditional hypothesis-directed methods of experimentation and towards exploratory methods.

This paper sketches a causal account of scientific explanation designed to sustain the judgment that high-level, detail-sparse explanations—particularly those offered in biology—can be at least as explanatorily valuable as lower-level counterparts. The motivating idea is that complete explanations maximize causal economy: they cite those aspects of an event’s causal run-up that offer the biggest-bang-for-your-buck, by costing less (in virtue of being abstract) and delivering more (in virtue making the event stable or robust).

In What Science Knows, the Australian philosopher and mathematician James Franklin explains in captivating and straightforward prose how science works its magic. It offers a semipopular introduction to an objective Bayesian/logical probabilist account of scientific reasoning, arguing that inductive reasoning is logically justified (though actually existing science sometimes falls short). Its account of mathematics is Aristotelian realist.

Just before the Scientific Revolution, there was a "Mathematical Revolution", heavily based on geometrical and machine diagrams. The "faculty of imagination" (now called scientific visualization) was developed to allow 3D understanding of planetary motion, human anatomy and the workings of machines. 1543 saw the publication of the heavily geometrical work of Copernicus and Vesalius, as well as the first Italian translation of Euclid.

Modern philosophy of mathematics has been dominated by Platonism and nominalism, to the neglect of the Aristotelian realist option. Aristotelianism holds that mathematics studies certain real properties of the world – mathematics is neither about a disembodied world of “abstract objects”, as Platonism holds, nor it is merely a language of science, as nominalism holds. Aristotle’s theory that mathematics is the “science of quantity” is a good account of at least elementary mathematics: the ratio of two heights, for example, is (...) a perceivable and measurable real relation between properties of physical things, a relation that can be shared by the ratio of two weights or two time intervals. Ratios are an example of continuous quantity; discrete quantities, such as whole numbers, are also realised as relations between a heap and a unit-making universal. For example, the relation between foliage and being-a-leaf is the number of leaves on a tree,a relation that may equal the relation between a heap of shoes and being-a-shoe. Modern higher mathematics, however, deals with some real properties that are not naturally seen as quantity, so that the “science of quantity” theory of mathematics needs supplementation. Symmetry, topology and similar structural properties are studied by mathematics, but are about pattern, structure or arrangement rather than quantity. (shrink)

Though biologists identify individuals as ‘male’ or ‘female’ across a broad range of animal species, the particular traits exhibited by males and females can vary tremendously. This diversity has led some to conclude that cross-animal sexes (males, or females, of whatever animal species) have “little or no explanatory power” (Dupré 1986: 447) and, thus, are not natural kinds in any traditional sense. This essay will explore considerations for and against this conclusion, ultimately arguing that the animal sexes, properly understood, are (...) “historical explanatory kinds”: groupings that can be scientifically significant even while their members differ radically in their current properties and particular histories. Whether this makes them full-fledged natural kinds is a question I take up at the very end. (shrink)

How were reliable predictions made before Pascal and Fermat's discovery of the mathematics of probability in 1654? What methods in law, science, commerce, philosophy, and logic helped us to get at the truth in cases where certainty was not attainable? The book examines how judges, witch inquisitors, and juries evaluated evidence; how scientists weighed reasons for and against scientific theories; and how merchants counted shipwrecks to determine insurance rates. Also included are the problem of induction before Hume, design arguments for (...) the existence of God, and theories on how to evaluate scientific and historical hypotheses. It is explained how Pascal and Fermat's work on chance arose out of legal thought on aleatory contracts. The book interprets pre-Pascalian unquantified probability in a generally objective Bayesian or logical probabilist sense. (shrink)

The objective Bayesian view of proof (or logical probability, or evidential support) is explained and defended: that the relation of evidence to hypothesis (in legal trials, science etc) is a strictly logical one, comparable to deductive logic. This view is distinguished from the thesis, which had some popularity in law in the 1980s, that legal evidence ought to be evaluated using numerical probabilities and formulas. While numbers are not always useful, a central role is played in uncertain reasoning by the (...) ‘proportional syllogism’, or argument from frequencies, such as ‘nearly all aeroplane flights arrive safely, so my flight is very likely to arrive safely’. Such arguments raise the ‘problem of the reference class’, arising from the fact that an individual case may be a member of many different classes in which frequencies differ. For example, if 15 per cent of swans are black and 60 per cent of fauna in the zoo is black, what should I think about the likelihood of a swan in the zoo being black? The nature of the problem is explained, and legal cases where it arises are given. It is explained how recent work in data mining on the relevance of features for prediction provides a solution to the reference class problem. (shrink)

Antitheodicy objects to all attempts to solve the problem of evil. Its objections are almost all on moral grounds—it argues that the whole project of theodicy is morally offensive. Trying to excuse God’s permission of evil is said to deny the reality of evil, to exhibit gross insensitivity to suffering, and to insult the victims of grave evils. Since antitheodicists urge the avoidance of theodicies for moral reasons, it is desirable to evaluate the moral reasons against theodicies in abstraction from (...) the intellectual reasons for and against them. It is argued that the best known theodicies such as those based on soul-making and free will are guilty of moral faults as alleged. But Leibniz’s best of all possible worlds theory, often thought to be the most morally offensive ‘Panglossian’ theodicy, is morally blameless because it excuses God by the absolute impossibility of his choosing any world better than the present one. Theodicy should not be conceived of as a search for greater goods which may excuse God’s permitting evils. From the divine point of view, creation is an upfront choice between scenarios—in modern parlance, a Trolley problem rather than a Transplant problem. In cases of forced choice among scenarios, it is morally improper to criticize one who chooses the best. (shrink)

Philosophical discussions of species have focused on multicellular, sexual animals and have often neglected to consider unicellular organisms like bacteria. This article begins to fill this gap by considering what species concepts, if any, apply neatly to the bacterial world. First, I argue that the biological species concept cannot be applied to bacteria because of the variable rates of genetic transfer between populations, depending in part on which gene type is prioritized. Second, I present a critique of phylogenetic bacterial species, (...) arguing that phylogenetic bacterial classification requires a questionable metaphysical commitment to the existence of essential genes. I conclude by considering how microbiologists have dealt with these biological complexities by using more pragmatic and not exclusively evolutionary accounts of species. I argue that this pragmatism is not borne of laziness but rather of the substantial conceptual problems in classifying bacteria based on any evolutionary standard. (shrink)

Fifty years of effort in artificial intelligence (AI) and the formalization of legal reasoning have produced both successes and failures. Considerable success in organizing and displaying evidence and its interrelationships has been accompanied by failure to achieve the original ambition of AI as applied to law: fully automated legal decision-making. The obstacles to formalizing legal reasoning have proved to be the same ones that make the formalization of commonsense reasoning so difficult, and are most evident where legal reasoning has to (...) meld with the vast web of ordinary human knowledge of the world. Underlying many of the problems is the mismatch between the discreteness of symbol manipulation and the continuous nature of imprecise natural language, of degrees of similarity and analogy, and of probabilities. (shrink)

Nearly all defences of the agent-causal theory of free will portray the theory as a distinctively libertarian one — a theory that only libertarians have reason to accept. According to what I call ‘the standard argument for the agent-causal theory of free will’, the reason to embrace agent-causal libertarianism is that libertarians can solve the problem of enhanced control only if they furnish agents with the agent-causal power. In this way it is assumed that there is only reason to accept (...) the agent-causal theory if there is reason to accept libertarianism. I aim to refute this claim. I will argue that the reasons we have for endorsing the agent-causal theory of free will are nonpartisan. The real reason for going agent-causal has nothing to do with determinism or indeterminism, but rather with avoiding reductionism about agency and the self. As we will see, if there is reason for libertarians to accept the agent-causal theory, there is just as much reason for compatibilists to accept it. It is in this sense that I contend that if anyone should be an agent-causalist, then everyone should be an agent-causalist. (shrink)

Philosophers and social scientists of diverse orientations have suggested that the pragmatics of semiosis is germane to a dynamic account of meaning as process. Semiosis, the central focus of C. S. Peirce's pragmatic philosophy, may hold a key to perennial problems regarding meaning. Indeed, Peirce's thought should be deemed seminal when placed within the cognitive sciences, especially with respect to his concept of the sign. According to Peirce's pragmatic model, semiosis is a triadic, time-bound, context-sensitive, interpreter-dependent, materially extended dynamic process. (...) Semiosis involves inter-relatedness and inter-action between signs, their objects, acts and events in the world, and the semiotic agents who are in the process of making and taking them. (shrink)

The late scholastics, from the fourteenth to the seventeenth centuries, contributed to many fields of knowledge other than philosophy. They developed a method of conceptual analysis that was very productive in those disciplines in which theory is relatively more important than empirical results. That includes mathematics, where the scholastics developed the analysis of continuous motion, which fed into the calculus, and the theory of risk and probability. The method came to the fore especially in the social sciences. In legal theory (...) they developed, for example, the ethical analyses of the conditions of validity of contracts, and natural rights theory. In political theory, they introduced constitutionalism and the thought experiment of a “state of nature”. Their contributions to economics included concepts still regarded as basic, such as demand, capital, labour, and scarcity. Faculty psychology and semiotics are other areas of significance. In such disciplines, later developments rely crucially on scholastic concepts and vocabulary. (shrink)

In 1947 Donald Cary Williams claimed in The Ground of Induction to have solved the Humean problem of induction, by means of an adaptation of reasoning first advanced by Bernoulli in 1713. Later on David Stove defended and improved upon Williams’ argument in The Rational- ity of Induction (1986). We call this proposed solution of induction the ‘Williams-Stove sampling thesis’. There has been no lack of objections raised to the sampling thesis, and it has not been widely accepted. In our (...) opinion, though, none of these objections has the slightest force, and, moreover, the sampling thesis is undoubtedly true. What we will argue in this paper is that one particular objection that has been raised on numerous occasions is misguided. This concerns the randomness of the sample on which the inductive extrapolation is based. (shrink)

In this paper we propose an Ontology of Commercial Exchange (OCE) based on Basic Formal Ontology. OCE is designed for re-use in the Industrial Ontologies Foundry (IOF) and in other ontologies addressing different aspects of human social behavior involving purchasing, selling, marketing, and so forth. We first evaluate some of the design patterns used in the Financial Industry Business Ontology (FIBO) and Product Types Ontology (PTO). We then propose terms and definitions that we believe will improve the representation of contractual (...) obligations, sales processes, and their associated documents. A commercial exchange, for instance, involves mutual agreement to reciprocate actions, such as transferring money, performing a service, or transferring goods. (shrink)

It may be a myth that Plato wrote over the entrance to the Academy “Let no-one ignorant of geometry enter here.” But it is a well-chosen motto for his view in the Republic that mathematical training is especially productive of understanding in abstract realms, notably ethics. That view is sound and we should return to it. Ethical theory has been bedevilled by the idea that ethics is fundamentally about actions (right and wrong, rights, duties, virtues, dilemmas and so on). That (...) is an error like the one Plato mentions of thinking mathematics is about actions (of adding, constructing, extracting roots and so on). Mathematics is about eternal relations between universals, such as the ratio of the diagonal of a square to the side. Ethics too is about eternal verities, such as the equal worth of persons and just distributions. Mathematical and ethical verities do both constrain actions, such as the possibility of walking over the seven bridges of Königsberg once and once only or of justly discriminating between races. But they are not themselves about action. In principle, neither mathematical nor ethical verities are subject to historical forces or disagreement among tribes (though they can be better understood as time goes on). Plato is right: immersion in mathematics induces an understanding of the necessities underpinning reality, an understanding that is essential for distinguishing objective ethics from tribal custom. Equality, for example, is an abstract concept which is foundational for both mathematics and ethics. (shrink)

Pascal’s Wager does not exist in a Platonic world of possible gods, abstract probabilities and arbitrary payoffs. Real decision-makers, such as Pascal’s “man of the world” of 1660, face a range of religious options they take to be serious, with fixed probabilities grounded in their evidence, and with utilities that are fixed quantities in actual minds. The many ingenious objections to the Wager dreamed up by philosophers do not apply in such a real decision matrix. In the situation Pascal addresses, (...) the Wager is a good bet. In the situation of a modern Western intellectual, the reasoning of the Wager is still powerful, though the range of options and the actions indicated are not the same as in Pascal’s day. (shrink)

The abstract Latinate vocabulary of modern English, in which philosophy and science are done, is inherited from medieval scholastic Latin. Words like "nature", "art", "abstract", "probable", "contingent", are not native to English but entered it from scholastic translations around the 15th century. The vocabulary retains much though not all of its medieval meanings.

El objetivo de este artículo es presentar una demostración de un teorema clásico sobre álgebras booleanas y ordenes parciales de relevancia actual en teoría de conjuntos, como por ejemplo, para aplicaciones del método de construcción de modelos llamado “forcing” (con álgebras booleanas completas o con órdenes parciales). El teorema que se prueba es el siguiente: “Todo orden parcial se puede extender a una única álgebra booleana completa (salvo isomorfismo)”. Donde extender significa “sumergir densamente”. Tal demostración se realiza utilizando cortaduras de (...) Dedekind siguiendo el texto “Set Theory” de Jech, y otras ideas propias del autor de este artículo. Adicionalmente, se formulan algunas versiones débiles del axioma de elección relacionadas con las álgebras booleanas, las cuales son también de gran importancia para la investigación en teoría de conjuntos y teoría de modelos, pues estas son poderosas técnicas de construcción de modelos, como por ejemplo, el teorema de compacidad (permite construir modelos no estándar, etc) y el teorema del ultrafiltro, que permite construir ultraproductos (pueden ser usados para investigar problemas de cardinales grandes, etc). Se presentan algunas referencias de problemas abiertos sobre el tema. -/- The objective of this paper is to present a demonstration of a classical theorem on boolean algebras and partial orders of current relevance in set theory, as for example, for applications of model construction method called forcing" (with boolean algebras complete or with partial orders). The theorem to be proved is as follows: Any partial order can be extended to a single complete boolean algebra (up to isomorphism)". Where to extend means embed densely". Such a demonstration is done using Dedekind's cuts following the text Set Theory" of Jech, and other ideas of the author of this article. In addition, some weak versions of the axiom of choice related to boolean algebras are formulated, which are also of great importance for the research in set theory and model theory, since this are powerful model construction techniques, such as the compactness theorem (allows the construction of non-standard models, etc.) and the ultralter theorem, which allows the construction of ultraproducts (can be used to investigate problems of large cardinals, etc). Some references of open problems on the subject are presented. (shrink)

A problem for Aristotelian realist accounts of universals (neither Platonist nor nominalist) is the status of those universals that happen not to be realised in the physical (or any other) world. They perhaps include uninstantiated shades of blue and huge infinite cardinals. Should they be altogether excluded (as in D.M. Armstrong's theory of universals) or accorded some sort of reality? Surely truths about ratios are true even of ratios that are too big to be instantiated - what is the truthmaker (...) of such truths? It is argued that Aristotelianism can answer the question, but only a semi-Platonist form of it. (shrink)

• It would be a moral disgrace for God (if he existed) to allow the many evils in the world, in the same way it would be for a parent to allow a nursery to be infested with criminals who abused the children. • There is a contradiction in asserting all three of the propositions: God is perfectly good; God is perfectly powerful; evil exists (since if God wanted to remove the evils and could, he would). • The religious believer (...) has no hope of getting away with excuses that evil is not as bad as it seems, or that it is all a result of free will, and so on. Piper avoids mentioning the best solution so far put forward to the problem of evil. It is Leibniz’s theory that God does not create a better world because there isn’t one — that is, that (contrary to appearances) if one part of the world were improved, the ramifications would result in it being worse elsewhere, and worse overall. It is a “bump in the carpet” theory: push evil down here, and it pops up over there. Leibniz put it by saying this is the “Best of All Possible Worlds”. That phrase was a public relations disaster for his theory, suggesting as it does that everything is perfectly fine as it is. He does not mean that, but only that designing worlds is a lot harder than it looks, and determining the amount of evil in the best one is no easy matter. Though humour is hardly appropriate to the subject matter, the point of Leibniz’s idea is contained in the old joke, “An optimist is someone who thinks this is the best of all possible worlds, and a pessimist thinks.. (shrink)

The formal sciences - mathematical as opposed to natural sciences, such as operations research, statistics, theoretical computer science, systems engineering - appear to have achieved mathematically provable knowledge directly about the real world. It is argued that this appearance is correct.

Dispostions, such as solubility, cannot be reduced to categorical properties, such as molecular structure, without some element of dipositionaity remaining. Democritus did not reduce all properties to the geometry of atoms - he had to retain the rigidity of the atoms, that is, their disposition not to change shape when a force is applied. So dispositions-not-to, like rigidity, cannot be eliminated. Neither can dispositions-to, like solubility.

Among worldviews, in addition to the options of materialist atheism, pantheism and personal theism, there exists a fourth, “local emergentism”. It holds that there are no gods, nor does the universe overall have divine aspects or any purpose. But locally, in our region of space and time, the properties of matter have given rise to entities which are completely different from matter in kind and to a degree god-like: consciousnesses with rational powers and intrinsic worth. The emergentist option is compared (...) with the standard alternatives and the arguments for and against it are laid out. It is argued that, among options in the philosophy of religion, it involves the minimal reworking of the manifest image of common sense. Hence it deserves a place at the table in arguments as to the overall nature of the universe. (shrink)

The winning entry in David Stove's Competition to Find the Worst Argument in the World was: “We can know things only as they are related to us/insofar as they fall under our conceptual schemes, etc., so, we cannot know things as they are in themselves.” That argument underpins many recent relativisms, including postmodernism, post-Kuhnian sociological philosophy of science, cultural relativism, sociobiological versions of ethical relativism, and so on. All such arguments have the same form as ‘We have eyes, therefore we (...) cannot see’, and are equally invalid. (shrink)