Research misconduct remains an important problem in health research despite decades of local, national, regional, and international efforts to eliminate it. The ultimate goal of every health research project, irrespective of setting, is to produce trustworthy findings to address local as well as global health issues. To be able to lead or participate meaningfully in international research collaborations, individual and institutional capacities for research integrity are paramount. Accordingly, this paper concerns itself not only with individuals’ research skills but also with (...) institutional and national policies and governance. Such policies and governance provide an ethical scaffold for the production of knowledge and structure incentives. This paper’s operational definition of research therefore draws from Institute of Medicine’s articulation of health research as an inquiry that aims to produce knowledge about the structure, processes, or effects of personal health services; and from an existing health systems framework. The paper reviews the research regulatory environment and the ethics apparatus in Ghana, and describes a project jointly undertaken by Ghanaian researchers in collaboration with New York University to assess the perceived adequacy of current institutional practices, opportunities, and incentives for promoting RI. (shrink)

This review article provides a new perspective on the ethics of green nudging. We advance a new model for assessing the ethical permissibility of green nudges (GNs). On this model, which provides normative guidance for policymakers, a GN is ethically permissible when the intervention is (1) efficacious, (2) cost-effective, and (3) the advantages of the GN (i.e. reducing the environmental harm) are not outweighed by countervailing costs/harms (i.e. for nudgees). While traditional ethical objections to nudges (paternalism, etc.) remain potential normative (...) costs associated with GNs, any such costs must be weighed against the injunction to reduce environmental harm to third parties. (shrink)

I am grateful to Donald Ainslie, Lisa Austin, Michael Blake, Abraham Drassinower, David Dyzenhaus, George Fletcher, Robert Gibbs, Louis-Philippe Hodgson, Sari Kisilevsky, Dennis Klimchuk, Christopher Morris, Scott Shapiro, Horacio Spector, Sergio Tenenbaum, Malcolm Thorburn, Ernest Weinrib, Karen Weisman, and the Editors of Philosophy & Public Affairs for comments, and audiences in the UCLA Philosophy Department and Columbia Law School for their questions.

This book presents Robert S. Hartman’s formal theory of value and critically examines many other twentieth century value theorists in its light, including A.J. Ayer, Kurt Baier, Brand Blanshard, Paul Edwards, Albert Einstein, William K. Frankena, R.M. Hare, Nicolai Hartmann, Martin Heidegger, G.E. Moore, P.H. Nowell-Smith, Jose Ortega y Gasset, Charles Stevenson, Paul W. Taylor, Stephen E. Toulmin, and J.O. Urmson.

Kit Fine has proposed a new solution to what he calls ‘a familiar puzzle’ concerning modality and existence. The puzzle concerns the argument from the alleged truths ‘It is necessary that Socrates is a man’ and ‘It is possible that Socrates does not exist’ to the apparent falsehood ‘It is possible that Socrates is a man and does not exist’. We discuss in detail Fine’s setting up of the ‘puzzle’ and his rejection, with which we concur, of two mooted solutions (...) to it. (One of these uses standard, Kripkean, notions, and the other rests on work done by Arthur Prior.) We set out, and reject, the philosophy of modality underlying Fine’s new solution, and we defend an alternative response to the alleged puzzle. Our solution follows the work of David Wiggins in distinguishing between the sentential operator ‘It is necessary that’ and the predicate modifier ‘necessarily’. We briefly provide this distinction with a possible- world semantics on which it is neither a necessary truth, in some sense, that Socrates exists nor true, in some sense, that Socrates necessarily exists. (shrink)

DIFERENCIAÇÃO SEXUAL -/- Emanuel Isaque Cordeiro da Silva Instituto Agronômico de Pernambuco Embrapa Semiárido -/- • _____OBJETIVO -/- Os estudantes de Veterinária e de Zootecnia estão ligados à disciplina Reprodução Animal, um pelos mecanismos fisiológicos para evitar e tratar as possíveis patologias do trato reprodutivo dos animais domésticos, e outro para o entendimento dos processos fisiológicos visando o manejo reprodutivo e a procriação para a formação de um plantel geneticamente melhorado. Sendo assim, a finalidade do presente trabalho é apresentar os (...) mecanismos que regulam as diferenças sobre o desenvolvimento embrionário relativos à diferenciação e determinação sexual de machos e fêmeas, que também incluem o desenvolvimento dos órgãos envolvidos na reprodução e a origem das diferenças entre ambos os sexos. -/- •____INTRODUÇÃO -/- Os organismos que se reproduzem sexualmente são descendentes de organismos ao qual não existia a diferenciação sexual. Em algum momento da evolução surgiu a reprodução sexual como um mecanismo para incrementar a diversidade genética e facilitar a troca de informações genéticas mediante o material genético da fêmea com o do macho. Devido sua origem comum, na maioria das espécies, tanto os machos como as fêmeas possuem todos os genes necessários para desenvolverem-se em qualquer dos sexos. O que efetivamente faz diferença entre os sexos é a forma e a ordem ao qual se expressam os genes durante o processo de desenvolvimento. A diferenciação sexual é regulada principalmente por mecanismos epigenéticos, mais do que as diferenças genéticas de grande magnitude entre os sexos. Todo o controle epigenético de qualquer processo de desenvolvimento depende basicamente de uma série de expressões gênicas, através da qual a expressão de certa combinação de genes resulta na presença de determinadas proteínas, conhecidas como os fatores de transcrição, que induzem ou reprimem a expressão de outro(os) gene(es), a partir dos quais se produzem novas proteínas, que em certos casos também atuam como fatores de transcrição para outros genes, e assim sucessivamente. Logo, a expressão ou falta de expressão de um gene ao início da série pode resultar em um ladrão totalmente diferente da expressão de outros genes subsequentes, o que pode ocasionar profundas mudanças no processo de desenvolvimento e até a mutações indesejáveis. O padrão predeterminado de expressões gênica relativo a diferenciação sexual na maioria das espécies tanto domésticas quanto selvagens, leva ao desenvolvimento de um dos sexos (o padrão predeterminado dos mamíferos é o sexo feminino). Em consequência, a diferenciação faz com que um indivíduo do sexo oposto exija a expressão de um gene de determinação sexual que desvie a subsequente série de expressões gênica em direção ao dito sexo. Nos mamíferos, a expressão do gene SRY, localizado no cromossomo Y (e portanto ausente nas fêmeas), redige o padrão de diferenciação sexual de sua via pré-estabelecida feminina em direção ao padrão masculino. A existência de uma única diferença genética (presença do gene SRY nos machos e ausentes nas fêmeas), vai se amplificando e termina resultando no desenvolvimento de indivíduos diferentes entre si. Esse é um mecanismo de diferenciação sexual cromossômica. O primeiro passo de uma série de diferenciação sexual, em sentido estrito, não depende nem requer necessariamente a presença de um gene diferente em algum dos sexos. O gene “disparador” da diferenciação sexual pode estar presente em todos os embriões, porém pode expressar-se somente em algum deles, devido a fatores ambientais que formam parte da sua regulação epigenética, isto é, uma determinação sexual ambiental. Em algumas espécies de tartarugas ou de lagartos a expressão ou falta de expressão do gene “disparador”, por exemplo, depende da temperatura existente durante a incubação dos ovos, pelo qual alguns embriões desenvolvem-se como machos e outros como fêmeas, apesar de não existir diferença genética entre eles, simplesmente como consequência da temperatura: a determinação sexual depende da temperatura a que cada um deles foi submetido durante a incubação. Em certas espécies as temperaturas mais elevadas facilitam o desenvolvimento de fêmeas e outras de machos, enquanto que em outras espécies as temperaturas amenas (intermediárias) resultam em machos, e as inferiores como as superiores induzem o desenvolvimento de fêmeas. A existência dessa diversidade indica que a temperatura por si mesma não é a que induz ou a que provoca o desenvolvimento do macho e da fêmea, senão a que atua somente como um regulador inicial da diferenciação sexual. Em outras espécies o fator ambiental que regula a determinação sexual pode ser distinto. A densidade populacional, por exemplo, pode atuar como um regulador. Podemos concluir que a determinação sexual dependente da temperatura ou de outros fatores ambientais estabelece-se antes da determinação sexual cromossômica, a qual evoluiu depois como um método que oferece maior certeza e resultado, já que a proporção de machos e fêmeas não é afetada por mudanças ambientais ou de hábitat. -/- •___FORMAÇÃO INICIAL DA GÔNADA -/- Basicamente em todos os embriões, inicialmente se formam as chamadas gônadas indiferenciadas (com o potencial de desenvolver-se em ovários ou testículos) a partir da invasão das cristas genitais pelas células germinais primordiais, que migram desde seu local de origem no epiblasto, perto do lugar onde o saco vitelino se une com o intestino primitivo e que chegam até às cristas genitais que são engrossamentos de tecido situados na região mesonéfrica do embrião. A migração das células germinais primordiais ocorre muito cedo sobre o processo de desenvolvimento do embrião (dia 26 nos bovinos). Ao chegas as cristas genitais, as células germinativas proliferam-se e se organizam com as células somáticas já existentes nas cristas para ir formando a gônada (figura 1). Para regular essa remodelação e conformação adequada da gônada vários genes se expressam, como o OCT-4 (que aparentemente mantém a totipotencialidade da gônada), assim como o SF-1 (Fator esteroidogênico 1) e o WT-1 (gene associado ao tumor de Wilms). Esses dois últimos genes estimulam a proliferação celular e estabelecimento dos cordões sexuais. Nessa etapa inicial do desenvolvimento todos esses genes se expressam sem distinção de sexo, pelo que a gônada em formação mantém a capacidade de se diferenciar em testículo ou em ovário. -/- Figura 1: migração das células germinais primordiais em direção a crista gonodal. Diferenciação das gônadas femininas e masculinas. Fonte: ZARCO, 2018. -/- •___SEXO CROMOSSÔMICO -/- Têm-se observado que nos mamíferos a determinação sexual depende diretamente dos cromossomos. As fêmeas possuem dois cromossomos sexuais X (um contribuído do óvulo e o outro por um espermatozoide “X”). Os machos, por sua vez, possuem um cromossomo sexual X(proveniente do óvulo) e um cromossomo sexual Y, que provém de um espermatozoide “Y” (figura 2). A metade dos espermatozoides produzidos por um macho são X e a metade Y, isso porque durante a espermatogênese a divisão meiótica provoca que a partir de cada espermatócito primário, célula diploide que por pertencer a um indivíduo macho tem um cromossomo X e um Y, se originem das espermátides haploides a cada um das que eles tocam cromossomos X, e outras espermátides haploides as que eles tocam os cromossomos Y. Dessa forma, de acordo com o tipo do espermatozoide que fertilize o ovócito, se originará um indivíduo com cariótipo feminino “XX” ou um cariótipo masculino “XY” (figura 2). Esse processo é conhecido como sexo cromossômico, ao qual se determina o momento da fertilização. Figura 2: nos mamíferos todos os óvulos produzidos pelas fêmeas possuem um cromossomo sexual X. A metade dos espermatozoides produzidos pelos machos possuem um cromossomo X e a outra metade possui um cromossomo Y. Dependendo do cromossomo presente no espermatozoide que fertilize o óvulo pode-se gerar um indivíduo XX (fêmea) ou um XY (macho). Fonte: ZARCO, 2018. -/- O cromossomo “Y” é uma “invenção” relativamente recente na história da evolução das espécies e do estudo da genética. Surgiu a partir de uma mutação de um cromossomo “X”, que resultou na perda de um de seus braços, que é por onde se originou a morfologia do cromossomo Y. A maioria dos genes presentes no cromossomo Y também existem no cromossomo X; assim mesmo somente alguns genes do cromossomo Y foram evoluídos até ser diferentes dos genes do cromossomo X. Embora os machos possuam um cromossomo que não está presente nas fêmeas, esse mesmo cromossomo não aporta toda a informação genética original. Todos os genes existentes nas fêmeas estão também presentes nos dos machos, já que eles também possuem um cromossomo X. Uma particularidade do cromossomo Y, ao existir somente uma cópia nos machos, é que ele sofre um entrecruzamento com um cromossomo análogo durante o processo de meiose, pelo que o cromossomo Y de um macho é idêntico ao de seu progenitor e ao de seus descendentes, exceto no caso em que ocorra uma mutação espontânea. Em contraste, os cromossomos X das fêmeas (um proveniente do pai e outro da mãe) se entrecruzam durante a meiose, por onde cada óvulo produzido pela fêmea terá uma combinação de alelos distinta em seu cromossomo X. Ao estudar as diferenças presentes na sequência de DNA do cromossomo Y, é possível identificar a distância filogenética entre os indivíduos (quanto mais diferenças existirem entre os cromossomos significa que seu ancestral comum está mais longe). Algo análogo ocorre com o DNA das mitocôndrias, que sempre são aportados pela mãe e nunca sofrem recombinação genética. Gene SRY -/- Um dos poucos genes do cromossomo Y que não possuem correspondência com o cromossomo X é o gene SRY (Sex-determining Region of the Y chromossome – região do cromossomo Y determinante do sexo). Esse gene se expressa somente na gônada em formação nos embriões machos, em particular em células precursoras das células de Sertoli; ele codifica uma proteína da família SOX (SRY-like Box) que é uma família formada por proteínas que possuem um domínio de união ao DNA e que atuam como fatores de transcrição. Ao produzir-se a proteína SRY nas células precursoras das células de Sertoli estimula-se a expressão (transcrição) de outro gene análogo, denominado SOX-9 que, por sua vez, atua como um fator de transcrição que ativa a expressão de outros genes, como o FGF-9 (Fibroblast Growth Factor-9), ou seja ele é o estimulante de ativação dos demais. Os produtos dos genes SOX-9 e FGF-9 iniciam uma cascata de expressões que provocam a diferenciação das células de suporte da gônada indiferenciada (crista genital) em células de Sertoli. Em seguida, essas células dirigem a diferenciação das células intersticiais da crista genital em células de Leydig, o que finalmente resulta na formação de um testículo. Outro dos efeitos da proteína codificada por SOX-9 é um estímulo maior da expressão de seu próprio gene, pelo qual é produzido um ciclo de retroalimentação positiva que favorece a continuidade do processo de formação testicular. Como nos embriões da fêmea não existe o gene SRY, a gônada indiferenciada não é estimulada para expressar os genes SOX-9 nem o FGF-9 nas células de suporte (que nesse caso serão precursoras de células da granulosa). A gônada, em mudança, expressa em forma constitutiva, isto é, sem a necessidade de estimulação, outra cascata de genes que incluem o WNT4 (Wingless-integration Factor 4) e o RAPO1 (Respondina-1), que por sua vez iniciam uma cascata de expressão gênica, a qual provoca a diferenciação das células somáticas da gônada indiferenciada para formação das células da granulosa e células da teca, esse feito conduz, por sua vez, a formação de um ovário. No embrião macho a proteína SOX-9 inibe a expressão dos genes WNT4 e RSPO-1, pelo que a presença do gene SRY, e portanto de SOX-9, inibem a formação de um ovário ao mesmo tempo que estimulam a formação do testículo (figura 3). Em suma, se o embrião possui genótipo XY (um embrião macho), o gene SRY começa a expressar-se sobre as células precursoras da gônada imediatamente depois da formação da mesma, quando os cordões sexuais primários estão se desenvolvendo na medula. A expressão do gene, assim como a presença subsequente das proteínas SOX-9 e FGF-9 estimula a distinção das células de Sertoli e que se organizem os tubos seminíferos a partir dos cordões sexuais primários. Em contrapartida, em um embrião com genótipo XX (fêmea) não existe o gene SRY, pelo qual é impossível que se elevem os níveis das proteínas SOX-9 e FGF-9 e as células precursoras não se diferenciam em células de Sertoli, e portanto os cordões sexuais primários sofrem regressão. Depois de alguns dias, começam a organizar-se os cordões sexuais secundários e as células precursoras iniciam a expressão do gene WNT4, o que leva as mesmas a diferenciar-se em células da granulosa, que serão a base para a conformação dos folículos ovarianos. Se em um embrião XY, macho, a expressão do gene SRY demora, é formada um ovo-testículo devido a que algumas das células somáticas das cristas gonodais começam a expressar o gene WNT4, e a diferenciar-se em células da granulosa, enquanto que em outras a proteína SRY chega a tempo para dirigir a diferenciação para formação das células de Sertoli. No ovário em formação é expressado um gene denominado DAX-1 (Dosage-sensitive Sex Reversal). Esse gene, localizado no cromossomo X, codifica uma proteína que é um membro da família dos receptores nucleares ao que lhe falta o domínio de união ao DNA, pelo que parece atuar no bloqueio de diversos fatores de transcrição, entre os que se encontra o SRY. Como a proteína DAX-1 impede a ação da proteína SRY, um excesso de expressão do gene DAX-1 pode provocar a feminilização gonodal de indivíduos XY, macho, embora tenham SRY. Em condições normais, a expressão adequada do gene DAX-1 não é capaz de evitar a masculinização gonodal de embriões com o gene SRY, daqui o nome de reversão sexual dependente da dose. Figura 3: série de expressão gênica para a determinação gonodal. SRY (Região do cromossomo Y determinante do sexo), SOX-9 (SRY-like Box-9), FGF-9 (Fator de crescimento de fibroblastos-9), WNT4 (Wingless-integration Factor-4), RSPO-1 (Respondina-1). Uma vez que o SRY induz a expressão de SOX-9 na gônada masculina, inicia-se um processo de feedback positivo mediante o qual os níveis de expressão de SOX-9 e FGF-9 vão aumentando, ao mesmo tempo que inibem a expressão de WNT-4 e RSPO-1. Na gônada feminina não se expressam SRY, SOX-9 e nem FGF-9, o que permite que se expressem os genes WNT-4 e RSPO-1, que iniciam uma cascata de sinalização que dirige a formação de um ovário. Fonte: ZARCO, 2018. -/- • ___DIFERENCIAÇÃO SEXUAL DOS GENITAIS -/- Uma vez que se formam os testículos, todo o desenvolvimento subsequente dos órgãos e as características “masculinas” em lugar das femininas é em consequência dos hormônios produzidos pelos testículos em formação, incluindo os andrógenos e o hormônio inibidor dos ductos de Müller. Mediante a ausência de testículos todo o desenvolvimento dos órgãos genitais internos e externos segue um padrão feminino, sem levar em conta se estão presentes os ovários; o que significa a ausência de hormônios gonodais determina que o embrião se desenvolva como fêmea, uma vez que não requerem hormônios ovarianos para desencadear o padrão feminino. Por sua vez, as gônadas masculinas (os testículos), produzem substâncias que desviam o desenvolvimento em direção ao padrão masculino. Sob etapas relativamente rápidas da diferenciação todos os embriões possuem dois pares de dutos sexuais, os dutos de Wolff ou mesonéfricos e os dutos de Müller ou paramesonéfricos (figura 4). A testosterona secretada pelos testículos do feto macho em desenvolvimento atua sobre os dutos de Wolff, o que induz a formação posterior dos dutos deferentes, do epidídimo e das glândulas seminais (figura 4). Figura 4: formação dos órgãos genitais internos a partir dos dutos de Wolff no macho e dos dutos de Müller na fêmea. Fonte: ZARCO, 2018. -/- Os testículos produzem ao mesmo tempo, uma glicoproteína chamada Hormônio Inibidor dos Dutos de Müller (Müllerian Inhibiting Hormone, MIH, também chamado de Anti-Müllerian Hormone, AMH); como o seu nome indica, inibe o desenvolvimento dos dutos de Müller ou paramesonéfricos, provocando sua regressão, que impede a formação dos órgãos genitais característicos da fêmea como os ovidutos, o útero, a cérvix e a porção cranial da vagina (figura 4). O MIH é uma glicoproteína da família dos fatores de crescimento transformativo β (TGFβ). O gene MIH possui locais de união para os produtos dos genes SOX-9 e SF-1, pelo que a presença simultânea de ambos fatores de transcrição é necessária para a secreção do MIH e leva a cabo sua função de iniciação dos dutos de Müller sobre o embrião macho (vale lembrar que nessa etapa tanto a gônada de embriões machos como de embriões fêmeas expressam o gene SF-1, mas somente o macho expressa o SOX-9, para que unicamente esse último produza MIH). O certo é que na gônada do embrião fêmea não se produzem quantidades importantes da proteína SOX-9, além de que se produz a proteína DAX-1, mesma que antagoniza tanto a SOX-9 como a SF-1, todo o qual impede a produção de MIH e resulta no desenvolvimento dos dutos de Müller até a formação dos ovidutos, útero, cérvix e a porção cranial da vagina (figura 4). Assim, na fêmea, ao não haver testículos não circulam concentrações elevadas de andrógenos, o que impedirá o desenvolvimento dos dutos de Wolff, enquanto que os dutos de Müller se desenvolvem já que não haverá a presença do MIH para impedi-lo. O desenvolvimento dos genitais internos e externos femininos não requerem a presença de nenhum hormônio ovariano o que levará a cabo de maneira predeterminada (ou pré-estabelecida) na ausência de testículos. Outra estrutura interna que também se desenvolve de forma distinta nos machos e nas fêmeas é o seio urogenital, que no embrião macho é estimulado pela testosterona para formação da próstata, das glândulas bulbouretrais e da uretra peniana, enquanto que na fêmea forma a porção caudal da vagina. A respeito dos órgãos genitais externos (figura 5), nos embriões de ambos os sexos existem estruturas precursoras chamadas de tubérculo genital e pregas vestibulares. Na fêmea o tubérculo genital da origem ao clitóris e as pregas vestibulares dão origem aos lábios vulvares sem a necessidade da atuação de hormônios ovarianos, já que o padrão “por via pré-estabelecida” é feminino. Em contrapartida, no macho, tanto o tubérculo genital quanto as pregas vestibulares respondem ao hormônio 5α-dehidro-testosterona (DHT), ao qual se formam as células da pele da zona genital a partir da testosterona que é secretada pelos testículos. Para isso existem nas células a enzima 5α-reductasa, que transforma a testosterona em DHT. Uma vez formada, a DHT atua sobre as pregas vestibulares do embrião macho para que se fusionem e formem o escroto (em lugar dos lábios vulvares), e sobre o tubérculo genital para formar o pênis (em lugar do clitóris). Figura 5: estruturas que se desenvolvem nos embriões de cada sexo a partir do seio urogenital, o tubérculo genital e as pregas vestibulares. A cor do né de cada estrutura final corresponde com a cor do nome da estrutura a partir da qual se originou. Fonte: ZARCO, 2018. -/- • ___DIFERENCIAÇÃO SEXUAL DO SISTEMA NERVOSO -/- Existem inúmeras diferenças funcionais entre o sistema nervoso da fêmeas e o do machos, em humanos podem incluir diferenças tão complexas como a maior capacidade de verbal da mulher ou a maior capacidade de orientação espacial do homem. Nessa parte será abordada aquelas diferenças que influenciam diretamente sobre a função reprodutiva, como as diferenças na regulação da secreção de gonadotropinas ou as diferenças na capacidade de comportamento sexual masculino ou feminino. É necessário lembrar que, apesar de que essas diferenças se originem durante um período crítico da vida fetal ou neonatal (dependendo da espécie), geralmente se fazem presentes até que o animal chegue a vida adulta e demonstre obter ou não a capacidade para se comportar como macho ou como fêmea uma vez que é exposto aos hormônios sexuais que são secretada depois da puberdade. Igualmente aos processos acima citados, podemos afirmar que nos mamíferos o padrão pré-estabelecido de comportamento sexual e de secreção de gonadotropinas é o feminino. Se durante os primeiros dias de vida neonatal uma rata fêmea não é exposta a nenhum hormônio gonodal, ao chegar a vida adulta ela terá a capacidade de se comportar como fêmea na presença de estrógenos, assim como de secretar um pico pré-ovulatório de GnRH/LH em resposta aos mesmos (figura 6). Essa rata, portanto, não poderá se comportar como macho embora que em sua vida adulta seja exposta a testosterona. O sistema nervoso do rato macho recém-nascido que é exposto aos andrógenos produzidos pelos testículos, em detrimento, faz com que adquiram o potencial para se comportar como machos em sua vida adulta e que perdem o potencial para ter conduta de fêmeas na presença e/ou administração de estrógenos (processo conhecido como desfeminização do SNC). Se por meios de experimentos injetamos testosterona em uma rata fêmea recém-nascida, essa rata não poderá se comportar como fêmea em sua vida adulta, e passará a se comportar como macho. A castração neonatal de um rato (visando evitar a exposição de seu SNC a andrógenos testiculares), assim mesmo, resultará em sua vida adulta um padrão feminino (SNC feminizado e não masculinizado). O hipotálamo das ratas adultas possui uma área em que o número, características e densidade dos corpos neurais difere em machos e fêmeas, essa área é denominada como “núcleo sexualmente dimórfico do hipotálamo”, e tem demonstrado que quando as ratas são tratadas com testosterona na vida neonatal, a morfologia de seu núcleo sexualmente dimórfico será masculinizado em sua vida adulta, enquanto que a castração neonatal de ratos resulta em um núcleo sexualmente dimórfico feminizado em sua vida adulta. Isso significa que a exposição ou não a testosterona na vida neonatal é o que determina que tipo de núcleo sexualmente dimórfico se desenvolverá, o que por sua vez está relacionado com o tipo de conduta que o animal poderá expressar em sua vida adulta. Não deixa de ser um paradoxo que ao injetar uma dose elevada de estrógenos nos primeiros dias de vida de uma rata, os núcleos sexualmente dimórficos da mesma se desenvolverão como macho e em sua vida adulta seu potencial de conduta estará masculinizado e desfeminizado. O hormônio “feminino” conhecido como estradiol, masculiniza o hipotálamo e a conduta do animal. Logo, se a rata neonatal for exposta a injeção de andrógeno não-aromatizado (que não pode ser transformado em estrógenos pelas células) ela não se masculiniza. A masculinização e desfeminização dos ratos ou das ratas tratados com testosterona, na realidade, não são provocados pela própria testosterona, senão pelos estrógenos que se formam dentro dos neurônios quando absorvem a testosterona do sangue e a aromatizam para transformá-la em estrógenos (figura 6). Figura 6: desfeminização e masculinização do sistema nervoso central por meio da testosterona, que quando não absorvida pela α-fetoproteína pode entrar nos neurônios, onde se aromatizam para serem transformados em estrógenos, hormônio que é responsável pela desfeminização. Fonte: ZARCO, 2018. Por que as ratas, que possuem ovários funcionalmente produtores de estrógenos, não se masculinizam? A resposta está em uma proteína denominada α-fetoproteína que circula em altas concentrações nos fetos e nos recém-nascidos. Essa proteína possui a capacidade de unir-se aos estrógenos, ao qual impede seu entrada nas células. Os ratos, em desenvolvimento, produzem testosterona, no entanto não possui afinidade pela α-fetoproteína, o que permite com que ela circule livremente. Ao chegar ao SNC, a testosterona (que não foi absorvida) pode entrar nos neurônios e dentro deles se aromatizam e transformam-se em estrógenos, que finalmente masculinizam o SNC. A diferenciação sexual do hipotálamo depende, em síntese, da presença ou ausência dos testículos, o que permite que se produza ou não o hormônio testosterona que pode não ser absorvida por parte da α-fetoproteína, transformar-se em estrógenos e masculinizar o SNC. -/- •___CONCLUSÃO -/- Nos mamíferos todo o processo que se requerem para o desenvolvimento de um macho depende da existência de somente um gene do cromossomo Y, o gene SRY; a ausência desse gene resulta no desenvolvimento de uma fêmea. A presença ou ausência do gene SRY determina, então, a cadeia de eventos morfogênicos que ocorrerá em sua expressão ou não, para desenvolver todos os órgãos e características de um macho ou de uma fêmea. Por essa razão, os indivíduos com uma monossomia XOA (síndrome de Turner) são fêmeas (por não possuir o cromossomo Y nem o gene SRY), enquanto que os indivíduos triploides XXY (síndrome de Kleinefelter) são machos embora possuam dois cromossomos X. Em algumas espécies, no entanto, têm-se identificado machos que são cromossomicamente XX; nesses casos é determinado invariavelmente que por ser um erro durante a meiose a região do cromossomo Y em que reside o gene SRY tem sido transloucada ao cromossomo X. Da mesma forma, em alguns casos tem sido encontrado fêmeas com cariótipo XY; que nelas se identifica uma mutação inabilitante do gene SRY. Isso demonstra experimentalmente que por meio da engenharia genética é possível produzir machos com cariótipo XY mas com o gene SRY eliminado (knockout). Como é de se esperar, esses machos desenvolvem ovários e todos seus órgãos genitais, tanto internos quanto externos, e se desenvolvem como fêmeas. Os machos cromossomicamente XX transgênicos aos que se insertam uma cópia do gene SRY, desenvolvem testículos e um fenótipo masculino, embora sejam estéreis por causa da ausência de alguns genes do cromossomo Y que são necessários para a realização de uma espermatogênese normal. As falhas nos mecanismos de diferenciação sexual podem, diretamente, ocasionar anormalidades como as observadas nas bezerras Freemartin, que são bezerras originadas de uma gestação gemelar em que seu gêmeo era macho. O que sucede é que na espécie bovina, quando há uma gestação gemelar, é produzido um certo grau de anastomose entre as placentas dos fetos, o que permite a troca de sangue e de células entre ambos. Os produtos recebem, então, algumas células de seu gêmeos, que encontram seu lugar no órgão correspondente e se integram a ele. No caso particular das gônadas, quando o ovário primitivo de um embrião fêmea é colonizado por algumas células gonodais de seu gêmeo macho, essas células expressam o gene SRY, o que fará com que essa região da gônada se diferencie como testículo. Como resultado, se desenvolve um ovo-testículo (com maior ou menor proporção de tecido testicular dependendo do grau de colonização da gônada em formação por células provenientes do gêmeo macho). Ademais, ao haver certa quantidade de tecido testicular produtor de MIH, circularão sobre o feto fêmea níveis desse hormônio que, embora baixos, afetarão o desenvolvimento normal dos dutos de Müller, fazendo com que as bezerras Freemartin possuam genitálias internas ausentes ou pouco desenvolvidas. Os andrógenos produzidos pelas zonas de tecido testicular, por fim, são suficientes para causar um certo grau de masculinização, que se manifesta como um clitóris mais grande que o normal ou um desenvolvimento corporal masculinizado. -/- REFERÊNCIAS BIBLIOGRÁFICAS -/- ARNOLD, Arthur P.; CHEN, Xuqi; ITOH, Yuichiro. What a difference an X or Y makes: sex chromosomes, gene dose, and epigenetics in sexual differentiation. In: Sex and gender differences in pharmacology. Springer, Berlin, Heidelberg, 2013. p. 67-88. CUNNINGHAM, James. Tratado de fisiologia veterinária. Elsevier Health Sciences, 2011. DERIVAUX, Jules; BARNABÉ, Renato Campanarut. Reprodução dos animais domésticos. Zaragoza: Acribia, 1980. DA SILVA, Emanuel Isaque Cordeiro. Desenvolvimento Embrionário e Diferenciação Sexual nos Animais Domésticos. Disponível em:. Acesso em: Julho de 2020. HAFEZ, Elsayed Saad Eldin; HAFEZ, Bahaa. Reprodução animal. São Paulo: Manole, 2004. HIDALGO, C. Galina et al. Reproducción de animales domésticos. México: Limusa, 2008. MACLAUGHLIN, David T.; DONAHOE, Patricia K. Sex determination and differentiation. New England Journal of Medicine, v. 350, n. 4, p. 367-378, 2004. MCCARTHY, Margaret M.; ARNOLD, Arthur P. Reframing sexual differentiation of the brain. Nature neuroscience, v. 14, n. 6, p. 677, 2011. PLANT, Tony M.; ZELEZNIK, Anthony J. (Ed.). Knobil and Neill's physiology of reproduction. Academic Press, 2014. REY, Rodolfo. Diferenciación sexual embrio-fetal: De las moléculas a la anatomía. Revista chilena de anatomía, v. 19, n. 1, p. 75-82, 2001. SENGER, P. L. Embryogenesis of the pituitary gland and male or female reproductive system. In. Pathways to Pregnancy and Parturition. Current Conception Inc, v. 1, p. 8-76, 1997. ZARCO, L. Diferenciación sexual. In. PORTA, L. R.; MEDRANO, J. H. H. Fisiología reproductiva de los animales domésticos. Cidade do México: FMVZ-UNAM, 2018. -/- REALIZAÇÃO -/- . (shrink)

The field of textbooks in philosophy of mind is a crowded one. I shall consider six recent texts for their pedagogical usefulness. All have been published within the last five years, though two are new editions of previously published books. The first three are authored monographs: by K. T. Maslin, Barbara Montero, and André Kukla and Joel Walmsley. I then review three anthologies, each with two editors: William Lycan and Jesse Prinz, Brie Gertler and Lawrence Shapiro, and Brian McLaughlin (...) and Jonathan Cohen. These six texts constitute a diverse bunch. Within each of the two groups (monographs and anthologies), each individual text differs significantly from the other two in its approach, scope, and thus suitability for various levels of teaching. (shrink)

Saul Kripke once noted that there is a tight connection between computation and de re knowledge of whatever the computation acts upon. For example, the Euclidean algorithm can produce knowledge of which number is the greatest common divisor of two numbers. Arguably, algorithms operate directly on syntactic items, such as strings, and on numbers and the like only via how the numbers are represented. So we broach matters of notation. The purpose of this article is to explore the relationship between (...) the notations acceptable for computation, the usual idealizations involved in theories of computability, flowing from Alan Turing’s monumental work, and de re propositional attitudes toward numbers and other mathematical objects. (shrink)

Cognitive agents, whether human or computer, that engage in natural-language discourse and that have beliefs about the beliefs of other cognitive agents must be able to represent objects the way they believe them to be and the way they believe others believe them to be. They must be able to represent other cognitive agents both as objects of beliefs and as agents of beliefs. They must be able to represent their own beliefs, and they must be able to represent beliefs (...) as objects of beliefs. These requirements raise questions about the number of tokens of the belief representation language needed to represent believers and propositions in their normal roles and in their roles as objects of beliefs. In this paper, we explicate the relations among nodes, mental tokens, concepts, actual objects, concepts in the belief spaces of an agent and the agent's model of other agents, concepts of other cognitive agents, and propositions. We extend, deepen, and clarify our theory of intensional knowledge representation for natural-language processing, as presented in previous papers and in light of objections raised by others. The essential claim is that tokens in a knowledge-representation system represent only intensions and not extensions. We are pursuing this investigation by building CASSIE, a computer model of a cognitive agent and, to the extent she works, a cognitive agent herself. CASSIE's mind is implemented in the SNePS knowledge-representation and reasoning system. (shrink)

Many have begun to despair that climate justice will prevail even in a minimal form. The affective dimensions of such despair, we suggest, threaten to make climate action appear too demanding. Thus, despair constitutes a moral challenge to individual climate action that has not yet received adequate attention. In response, we defend a duty to act in hope for a more just (climate) future. However, as we see it, this duty falls differentially upon the shoulders of more and less advantaged (...) agents in society. From arguments by Black thinkers like Derrick Bell, we draw a set of distinctions between two types of hope: one for ideal justice, and one for more modest change; and between two types of hopeful actions, those undertaken through formal political channels and those we call 'extra-political' actions; and between two sites of differential moral burdens, those of the privileged and those of the oppressed. Ours is a case for facing even bleak realities, demanding otherwise, and acting in hope to achieve a better future. (shrink)

Brandom's "inferentialism"—his theory that contentfulness consists in being governed by inferential norms—proves dubiously compatible with his own deflationary approach to intentional objectivity. This is because a deflationist argument, adapted from the case of truth to that of correct inference, undermines the criterion of adequacy Brandom employs in motivating inferentialism. Once that constraint is abandoned, moreover, the very constitutive-explanatory availability of Brandom's inferential norms becomes suspect. Yet Brandom intertwines inferentialism with a separate explanatory project, one that in explaining the pragmatic significance (...) of meaning-attributions does yield a convincing construal of the claim that the concept of meaning is normative. (shrink)

Carl Gillett has defended what he calls the “dimensioned” view of the realization relation, which he contrasts with the traditional “flat” view of realization (2003, 2007; see also Gillett 2002). Intuitively, the dimensioned approach characterizes realization in terms of composition whereas the flat approach views realization in terms of occupiers of functional roles. Elsewhere we have argued that the general view of realization and multiple realization that Gillett advances is not able to discharge the theoretical duties of those relations ( (...) class='Hi'>Shapiro 2004, unpublished manuscript; Polger 2004, 2007, forthcoming). Here we focus on an internal objection to Gillett’s account and then raise some broader reasons to reject it. (shrink)

In this paper, I first present an overview of Asay’s _A Theory of Truthmaking_, highlighting what I take to be some of its most attractive features, especially his re-invigoration of the ontological understanding of truthmaking and his defence of ontology-first truthmaking over explanation-first truthmaking. Then, I articulate what I take to be a puzzling potential inconsistency: (a) he appeals to considerations to do with aboutness in criticising how well ontological views account for truth while (b) ruling out aboutness from the (...) right account of truthmaking. He argues, instead, that necessitation is both necessary and sufficient for truthmaking (§3.3). I suggest that adding aboutness to one’s account in the right way is not just compatible with but important for ontology-first truthmaking. I do all this to invite Asay to clarify his position on these matters. Overall, Asay’s worldview displays the fruitfulness of an ontologically serious approach to metaphysics that puts truthmaking centre-stage. (shrink)

Hofweber (Ontology and the ambitions of metaphysics, Oxford University Press, 2016) argues for a thesis he calls “internalism” with respect to natural number discourse: no expressions purporting to refer to natural numbers in fact refer, and no apparent quantification over natural numbers actually involves quantification over natural numbers as objects. He argues that while internalism leaves open the question of whether other kinds of abstracta exist, it precludes the existence of natural numbers, thus establishing what he calls “restricted nominalism” about (...) natural numbers. We argue that Hofweber’s internalism fails to establish restricted nominalism. Not only is his primary argument for restricted nominalism invalid, the analysis of quantification proposed threatens to collapse internalism into either a traditional form of error theory or realism. (shrink)

SNePS, the Semantic Network Processing System 45, 54], has been designed to be a system for representing the beliefs of a natural-language-using intelligent system (a \cognitive agent"). It has always been the intention that a SNePS-based \knowledge base" would ultimatelybe built, not by a programmeror knowledge engineer entering representations of knowledge in some formallanguage or data entry system, but by a human informing it using a natural language (NL) (generally supposed to be English), or by the system reading books or (...) articles that had been prepared for human readers. Because of this motivation, the criteria for the development of SNePS have included: it should be able to represent anything and everything expressible in NL; it should be able to represent generic, as well as speci c information; it should be able to use the generic and the speci c information to reason and infer information implied by what it has been told; it cannot count on any particular order among the pieces of information it is given; it must continue to act reasonably even if the information it is given includes circular de nitions, recursive rules, and inconsistent information. (shrink)

A central tenet of truthmaker theory is that necessitation is necessary for truthmaking (NEC). This paper defends NEC in a novel, piecemeal way, namely by responding to a potential counterexample involving a changing past. If Carter won a race at t1 but is later disqualified at t2, then Carter no longer won at t1. A wholly past event seems to have changed in the future. The event makes ‘Carter won the race at t1’ (RACE) true between t1‐2 but fails to (...) make it true at t2. So, we have a potential counterexample to necessitation: a truthmaker of RACE fails in another context to make the same truthbearer RACE true. I argue that the best solution to this challenge is not that there are different truthbearers at t1‐2 and t2 (the semantic response), or that RACE was never true because of the future disqualification or will always be true despite the future disqualification. The best solution is to accept that the past can change: past events can change based on what happens in the future (e.g., via their effects). This paper's novel defence of necessitation will illustrate the importance of utilising explicitly ontological and commonsensical tools in accounting for truth. (shrink)

Building on recent work, I present sequent systems for the non-classical logics LP, K3, and FDE with two main virtues. First, derivations closely resemble those in standard Gentzen-style systems. Second, the systems can be obtained by reformulating a classical system using nonstandard sequent structure and simply removing certain structural rules (relatives of exchange and contraction). I clarify two senses in which these logics count as “substructural.”.

This chapter first seeks to identify Huw Price's reasons for holding that "object naturalism" can be undermined by "subject-naturalistic" inquiry. It then addresses five questions about how his project bears on the prospects for a liberal naturalism. (1) Does Price’s strategy depend on his requirement that the relevant inquiry into human discourse and thought be conducted in natural-scientific terms? (2) Is Price’s strategy even compatible with that requirement? (3) Does the worldview Price arrives at amount to a liberal naturalism, i.e. (...) a naturalism that could be obtained by relaxing a more restrictive version? (4) Is Price’s strategy consistent with a liberal naturalism? (5) Should a proponent of Price’s strategy accept a liberal naturalism? (shrink)

Number words seemingly function both as adjectives attributing cardinality properties to collections, as in Frege’s ‘Jupiter has four moons’, and as names referring to numbers, as in Frege’s ‘The number of Jupiter’s moons is four’. This leads to what Thomas Hofweber calls Frege’s Other Puzzle: How can number words function as modifiers and as singular terms if neither adjectives nor names can serve multiple semantic functions? Whereas most philosophers deny that one of these uses is genuine, we instead argue that (...) number words, like many related expressions, are polymorphic, having multiple uses whose meanings are systematically related via type shifting. (shrink)

Two currently much discussed views about truth, truth pluralism and truth relativism, are found in Sellars’s writings. I show that his motivations for adoping these views are interestingly different from those shared by most of their recent advocates. First, I explain how Sellars comes to embrace a version of truth pluralism. I argue that his version overcomes a difficulty confronting pluralists, albeit at a serious cost. Then I argue that Sellars’s truth pluralism isn’t motivated by his interest in domains of (...) discourse beyond the “matter-of-factual.” Rather, the key to his truth pluralism, his analysis of truth as “semantical assertibility,” is motivated by the same consideration that leads him to adopt truth relativism. This is his interest in applying semantic notions to discourse that embodies conceptual structures other than ours. Despite their common motivation, I conclude that Sellars’s relativism is independent of, and indeed stands in tension with, the analysis of truth that underlies his pluralism. (shrink)

Successful athletic performance requires precision in many respects. A batter stands behind home plate awaiting the arrival of a ball that is less than three inches in diameter and moving close to 100 mph. His goal is to hit it with a ba­­t that is also less than three inches in diameter. This impressive feat requires extraordinary temporal and spatial coordination. The sweet spot of the bat must be at the same place, at the same time, as the ball. A (...) basketball player must keep a ball bouncing as she speeds from one end of the court to another, evading defensive players. She may never break pace as she lifts from the ground, throwing the ball fifteen feet toward a hoop that is eighteen inches in diameter. One task facing a psychologist involves explaining how the body does such things within the sometimes very demanding spatial and temporal constraints that a given task imposes. Part of the goal of this chapter is to sketch the commitments of an embodied approach to such an explanation. We shall see that an embodied account of motor skills draws concepts that depart radically from more traditional cognitivist theories of motor activity. Similarly, because an embodied approach to cognition introduces new ways to understand the human capacity for social interaction, it also promises to shed new light on how athletes coordinate their actions with each other. (shrink)

According to traditional logical expressivism, logical operators allow speakers to explicitly endorse claims that are already implicitly endorsed in their discursive practice — endorsed in virtue of that practice’s having instituted certain logical relations. Here, I propose a different version of logical expressivism, according to which the expressive role of logical operators is explained without invoking logical relations at all, but instead in terms of the expression of discursive-practical attitudes. In defense of this alternative, I present a deflationary account of (...) the expressive role of vocabulary by which we ascribe logical relations. (shrink)

Cells are cognitive entities possessing great computational power. DNA serves as a multivalent information storage medium for these computations at various time scales. Information is stored in sequences, epigenetic modifications, and rapidly changing nucleoprotein complexes. Because DNA must operate through complexes formed with other molecules in the cell, genome functions are inherently interactive and involve two-way communication with various cellular compartments. Both coding sequences and repetitive sequences contribute to the hierarchical systemic organization of the genome. By virtue of nucleoprotein complexes, (...) epigenetic modifications, and natural genetic engineering activities, the genome can serve as a read-write storage system. An interactive informatic conceptualization of the genome allows us to understand the functional importance of DNA that does not code for protein or RNA structure, clarifies the essential multidirectional and systemic nature of genomic information transfer, and emphasizes the need to investigate how cellular computation operates in reproduction and evolution. (shrink)

In this paper, we outline and critically evaluate Thomas Hofweber’s solution to a semantic puzzle he calls Frege’s Other Puzzle. After sketching the Puzzle and two traditional responses to it—the Substantival Strategy and the Adjectival Strategy—we outline Hofweber’s proposed version of Adjectivalism. We argue that two key components—the syntactic and semantic components—of Hofweber’s analysis both suffer from serious empirical difficulties. Ultimately, this suggests that an altogether different solution to Frege’s Other Puzzle is required.

A scholar of Hellenistic and Prussian history, Droysen developed a historical theory that at the time was unprecedented in range and depth, and which remains to the present day a valuable key for understanding history as both an idea and a professional practice. Arthur Alfaix Assis interprets Droysen’s theoretical project as an attempt to redefine the function of historiography within the context of a rising criticism of exemplar theories of history, and focuses on Droysen’s claim that the goal underlying (...) historical writing and reading should be the development of the subjective capacity to think historically. In addition, Assis examines the connections and disconnections between Droysen’s theory of historical thinking, his practice of historical thought, and his political activism. Ultimately, Assis not only shows how Droysen helped reinvent the relationship between historical knowledge and human agency, but also traces some of the contradictions and limitations inherent to that project. (shrink)

The authors developed this textbook in response to an increasing interest in ethics, and a growing number of courses on this topic that are now being offered in educational leadership programs. It is designed to fill a gap in instructional materials for teaching the ethics component of the knowledge base that has been established for the profession. The text has several purposes: First, it demonstrates the application of different ethical paradigms (the ethics of justice, care, critique, and the profession) through (...) discussion and analysis of real-life moral dilemmas that educational leaders face in their schools and communities. Second, it addresses some of the practical, pedagogical, and curricular issues related to the teaching of ethics for educational leaders. Third, it emphasizes the importance of ethics instruction from a variety of theoretical approaches. Finally, it provides a process that instructors might follow to develop their own ethics unit or course. * Part I provides an overview of why ethics is so important, especially for today's educational leaders, and describes a multiparadigm approach essential to practitioners as they grapple with ethical dilemmas. * Part II deals with the dilemmas themselves. Ethical dilemmas written by the authors' graduate students bring readers face-to-face with the kinds of dilemmas faced by practicing administrators in urban, suburban, and rural settings in an era full of complexities and contradictions. * Part III focuses on pedagogy and provides teaching notes for the instructor. The authors discuss the importance of self-reflection on the part of both instructors and students, and model how they thought through their own personal and professional ethical codes as well as reflected upon the critical incidents in their lives that shaped their teaching and frequently determined what they privileged in class. (shrink)

Bacteria do many things as organized populations. We have recently learned much about the molecular basis of intercellular communication among prokaryotes. Colonies display bacterial capacities for multicellular coordination which can be useful in nature where bacteria predominantly grow as films, chains, mats and colonies. E. coli colonies are organized into differentiated non-clonal populations and undergo complex morphogenesis. Multicellularity regulates many aspects of bacterial physiology, including DNA rearrangement systems. In some bacterial species, colony development involves swarming (active migration of cell groups). (...) Swarm colony development displays precise geometrical controls and periodic phenomena. Motile E. coli cells in semi-solid media form organized patterns due to chemotactic autoaggregation. On poor media, B. subtilis forms branched colonies using group motility and long-range chemical signalling. The significances of bacterial colony patterns thus reside in a deeper understanding of prokaryotic biology and evolution and in experimental systems for studying self-organization and morphogenesis. (shrink)

There is a remarkable trend in contemporary environmentalism that emphasizes ‘accepting responsibility’ for the natural world in contrast to outdated preservationist thinking that shirks such responsibility. This approach is often explained and justified by reference to the anthropocene: this fundamentally new epoch—defined by human domination—requires active human intervention to avert planetary catastrophe. However, in this paper, I suggest this rhetoric encourages a flight from history. This often jubilant, sometimes anxious, yearning for unprecedented human innovation and—ultimately—control in our new millennia mirrors (...) the Futurist movement that took off near the beginning of the last century. Despite the significant differences in the details of how academics have defended this twenty-first-century environmental outlook, they all represent the true flight from history; they too quickly jettison the ideas of historical environmentalists and so misunderstand the environmental values at the heart of preservation that are more salient than ever. (shrink)

Dilation occurs when an interval probability estimate of some event E is properly included in the interval probability estimate of E conditional on every event F of some partition, which means that one’s initial estimate of E becomes less precise no matter how an experiment turns out. Critics maintain that dilation is a pathological feature of imprecise probability models, while others have thought the problem is with Bayesian updating. However, two points are often overlooked: (1) knowing that E is stochastically (...) independent of F (for all F in a partition of the underlying state space) is sufficient to avoid dilation, but (2) stochastic independence is not the only independence concept at play within imprecise probability models. In this paper we give a simple characterization of dilation formulated in terms of deviation from stochastic independence, propose a measure of dilation, and distinguish between proper and improper dilation. Through this we revisit the most sensational examples of dilation, which play up independence between dilator and dilatee, and find the sensationalism undermined by either fallacious reasoning with imprecise probabilities or improperly constructed imprecise probability models. (shrink)

An appreciation of the life and word of Barbara McClintock, with special emphasis on what made her a unique and visionary scientist. The obituary indicates unappreciated aspects of her work on biological sensing and how organisms restructure their genomes in response to challenges.

Advocates of dynamic systems have suggested that higher mental processes are based on continuous representations. In order to evaluate this claim, we first define the concept of representation, and rigorously distinguish between discrete representations and continuous representations. We also explore two important bases of representational content. Then, we present seven arguments that discrete representations are necessary for any system that must discriminate between two or more states. It follows that higher mental processes require discrete representations. We also argue that discrete (...) representations are more influenced by conceptual role than continuous representations. We end by arguing that the presence of discrete representations in cognitive systems entails that computationalism (i.e., the view that the mind is a computational device) is true, and that cognitive science should embrace representational pluralism. (shrink)

We expound an alternative to the Copenhagen interpretation of the formalism of nonrelativistic quantum mechanics. The basic difference is that the new interpretation is formulated in the language of epistemological realism. It involves a change in some basic physical concepts. The ψ function is no longer interpreted as a probability amplitude of the observed behaviour of elementary particles but as an objective physical field representing the particles themselves. The particles are thus extended objects whose extension varies in time according to (...) the variation of ψ. They are considered as fundamental regions of space with some kind of nonlocality. Special consideration is given to the Heisenberg relations, the Einstein-Podolsky- Rosen correlations, the reduction process, the problem of measurement, and the quantum-statistical distributions. (shrink)

This paper examines the pressures leading two very different Early Modern philosophers, Descartes and Locke, to invoke two ways in which thought is directed at objects. According to both philosophers, I argue, the same idea can simultaneously count as “of” two different objects—in two different senses of the phrase ‘idea of’. One kind of intentional directedness is invoked in answering the question What is it to think that thus-and-so? The other kind is invoked in answering the question What accounts for (...) the success of our proper methods of inquiry? For Descartes as well as Locke, the two kinds of “ofness” come apart as a result of strong rationalist commitments. However, I will suggest that even if we reject such commitments, we go wrong if we assume that a single kind of intentional directedness suffices to address both questions. (shrink)

Withdrawal involves emotional pain that motivates much addictive behavior. In this paper, I argue that the emotional pain of withdrawal compels much addictive behavior. Researchers have noticed this possibility but it is widely underappreciated. Among philosophers, only Hanna Pickard has discussed emotional compulsion in addiction, and the emotional aspect of withdrawal has been almost completely neglected. Accounts of emotional compulsion in the philosophical literature (from Tappolet, Elster, and Furrow) probably do not capture how the distress of withdrawal compels, so I (...) propose a more suitable account of “pathodoxastic” compulsion in addiction. On this account, the emotional pain of withdrawal compels when it undermines the ability to believe that one can continue to endure it, and therefore the ability to intend abstinence. (shrink)

The present narrative review seeks to unravel where we are now, and where we need to go to delineate the active ingredients in psychotherapy delivered by conversational agents (e.g., chatbots). While psychotherapy delivered by conversational agents has shown promising effectiveness for depression, anxiety, and psychological distress across several randomized controlled trials, little emphasis has been placed on the therapeutic processes in these interventions. The theoretical framework of this narrative review is grounded in prominent perspectives on the active ingredients in psychotherapy. (...) Based on search terms derived from various theoretical perspectives, we conducted a systematic literature search of four scientific databases and identified 17 studies. Across the selected studies, three themes emerged: relationship variables, emotional venting, and cognitive factors. While methodological issues compromise the epistemic value of this evidence base, core questions also remain to be answered. Such questions include, but are not limited to, whether humans can form affectionate bonds to inanimate beings and whether these kind of mental health treatments should be understood as psychotherapy or something else. Researchers should therefore be cautious when applying theories of psychotherapy in the realm of conversational agents. We conclude the paper by introducing recommendations for future research, which we hope will help instigate methodologically sound studies in this field. (shrink)

A characterization result of dilation in terms of positive and negative association admits an extremal counterexample, which we present together with a minor repair of the result. Dilation may be asymmetric whereas covariation itself is symmetric. Dilation is still characterized in terms of positive and negative covariation, however, once the event to be dilated has been specified.

Determinism is established in quantum mechanics by tracing the probabilities in the Born rules back to the absolute (overall) phase constants of the wave functions and recognizing these phase constants as pseudorandom numbers. The reduction process (collapse) is independent of measurement. It occurs when two wavepackets overlap in ordinary space and satisfy a certain criterion, which depends on the phase constants of both wavepackets. Reduction means contraction of the wavepackets to the place of overlap. The measurement apparatus fans out the (...) incoming wavepacket into spatially separated eigenpackets of the chosen observable. When one of these eigenpackets together with a wavepacket located in the apparatus satisfy the criterion, the reduction associates the place of contraction with an eigenvalue of the observable. The theory is nonlocal and contextual. Keywords:. (shrink)

In "De l’Allemagne", Mme de Staël develops a sophisticated philosophical psychology that centers not on reason, but imagination. She does this by bringing French Enlightenment philosophy, particularly Rousseau and Diderot, into dialogue with German thinkers, including Kant and Herder. For Mme de Staël, imagination transcends the epistemic limits of sensibility and reason by incorporating sentiment.

The computational paradigm, which has dominated psychology and artificial intelligence since the cognitive revolution, has been a source of intense debate. Recently, several cognitive scientists have argued against this paradigm, not by objecting to computation, but rather by objecting to the notion of representation. Our analysis of these objections reveals that it is not the notion of representation per se that is causing the problem, but rather specific properties of representations as they are used in various psychological theories. Our analysis (...) suggests that all theorists accept the idea that cognitive processing involves internal information-carrying states that mediate cognitive processing. These mediating states are a superordinate category of representations. We discuss five properties that can be added to mediating states and examine their importance in various cognitive models. Finally, three methodological lessons are drawn from our analysis and discussion. (shrink)

Through a Gadamerian critique of Enlightenment objectivism, the discussion of right and wrong perception is based on the minimums of immediate illegitimizing of certain prejudices and the determining of one’s own perception as right or wrong in opposition to expertise; this ultimately allows knowledge to be laid out in an anti-relativist position whilst still permitting diversity of perception, proving that opinion necessitates its own change and development over time on both the micro and macro levels of thought.

According to Roman Ingarden, transcendental idealism prevented Kant from "even undertaking an attempt" at elucidating freedom "in terms of the causal structure of the world." I show that this claim requires qualification. In a remarkable series of Critical-period Reflexionen (5611-4, 5616-9), Kant sketches a defense of the possibility of freedom that differs radically from his published ones by incorporating an indeterministic account of the phenomena. Anticipating Łukasiewicz, he argues that universal causal determination is consistent with an open future: if an (...) action is contingent, there is an infinite regress of determining causes, yet there is a prior time at which this infinite series of causes has not yet commenced. However, he concedes that on this account the unity of experience "cannot fully obtain in the case of free beings." The fact that Kant even contemplated the indeterministic theory may carry implications for interpreting the argument of the Second Analogy. (shrink)

One prominent criticism of the abstractionist program is the so-called Bad Company objection. The complaint is that abstraction principles cannot in general be a legitimate way to introduce mathematical theories, since some of them are inconsistent. The most notorious example, of course, is Frege’s Basic Law V. A common response to the objection suggests that an abstraction principle can be used to legitimately introduce a mathematical theory precisely when it is stable: when it can be made true on all sufficiently (...) large domains. In this paper, we raise a worry for this response to the Bad Company objection. We argue, perhaps surprisingly, that it requires very strong assumptions about the range of the second-order quantifiers; assumptions that the abstractionist should reject. (shrink)

We present a game mechanic called pseudo-visibility for games inhabited by non-player characters (NPCs) driven by reinforcement learning (RL). NPCs are incentivized to pretend they cannot see pseudo-visible players: the training environment simulates an NPC to determine how the NPC would act if the pseudo-visible player were invisible, and penalizes the NPC for acting differently. NPCs are thereby trained to selectively ignore pseudo-visible players, except when they judge that the reaction penalty is an acceptable tradeoff (e.g., a guard might accept (...) the penalty in order to protect a treasure because losing the treasure would hurt even more). We describe an RL agent transformation which allows RL agents that would not otherwise do so to perform some limited self-reflection to learn the training environments in question. (shrink)

Ideas will always resist single-statement definitions, but in a rough attempt at generalization one can say that they either play or are attributed a very special role in thinking and expressive processes, in perhaps all domains of human culture. People who specialize in creating, receiving, transforming, and disseminating them are usually called “intellectuals”—even if they do not monopolize those social practices. The constitution and circulation of ideas as structures of thinking and expression, the settings in which they originate and to (...) which they respond, the material supports in which they are conveyed as well as the intellectual agents specialized in dealing with them are studied by the history of ideas and its neighboring fields. These include intellectual history, history of concepts, histoire des mentalités, Geistesgeschichte, history of books, and even cultural history, sociology of knowledge, and the histories of science, philosophy, literature, and the humanities. As it is obvious, such labels do not support a clear-cut division of labor, nor can they be lined up in an organogram that would fix constant hierarchical relations between them. They show up with incommensurable frequency, displaying different connotations within different academic cultures. This explains why in some cases—as in Geistesgeschichte, Begriffsgeschichte, or histoire des mentalités—equivalent English terms are considered problematic or unnecessary. Having flourished, spread, and sometimes also decayed within different national, disciplinary, and generational contexts, the fields designated by them can only have intricate and overlapping limits. A good way to understand the traditions connected to the history of ideas is hence to look closely to their messy border zones. The closest and most intricate connections are those between “history of ideas” and “intellectual history,” which is reflected in the fact that these terms are often employed interchangeably—a use that will be noted also in the remainder of the present text. Even so, “intellectual history” clearly emerged as preferential designation in the English-speaking world in the final decades of the twentieth century. A reason for this is the spread of the suspicion that “ideas” are burdened by essentialist traits that would render us insensitive to historical discontinuity. The notion of ideas is also sometimes regarded as much too oblivious of the way language conditions thought, and accordingly some analysts suggest that it would be out of line with the best theoretical intelligence established since the so-called linguistic turn (see Kelley 2002a: 310–14). However, others claim that ideas should not be equaled to expressed words, as they refer to occurrences that are best described with psychological terms such as beliefs and attitudes, and, further, that there would be non-essentialist ways of addressing them . What seems more uncontroversial is that, in comparison to “history of ideas,” “intellectual history” opens up an enlarged space of ambivalence as regards the analytical focus, which can then toggle from intellectual products to intellectual producers, consumers, and the cultural frameworks in which they interact. There are also important crossroads between the history of ideas and conceptual history (or Begriffsgeschichte), as both terms signal to the historical study of basic structures of thought. Conceptual history, however, at least in its most well-known variety, which was very much inspired by social-historical approaches, tends to be less centered on biographical and psychological issues and to introduce concepts as more depersonalized linguistic entities. Such and other connections and disconnections between the various ways of attending to “the reflective communal life of human beings in the past” (Burrow) will be further discussed in the following from the perspective of a geographically multicentered historical synopsis. Hopefully, its many limitations will be compensated by the possibilty of bringing to the fore relations that otherwise would not become so salient. (shrink)

Trata-se de um trabalho de natureza didática cujo propósito é introduzir o leitor à teoria da história de Jörn Rüsen. O texto inicia-se com uma introdução que situa este autor no contexto do desenvolvimento histórico da disciplina “teoria da história. Está dividido em três capítulos, nos quais os cinco componentes da sua “matriz disciplinar da ciência histórica são apresentados e discutidos, a saber (1) as carências de orientação e funções orientativas; (2) perspectivas diretoras da interpretação histórica e métodos de pesquisa (...) empírica; e (3) as formas de apresentação histórica. O trabalho finaliza-se com uma lista bibliográfica, da qual constam os títulos mais importantes de Rüsen, bem como uma série de comentários à sua teoria da história. (shrink)

What is history about? This Element shows that answers centred on the keyword 'past events' are incomplete, even if they are not simply wrong. Interweaving theoretical and historical perspectives, it provides an abstract overview of the thematic plurality that characterizes contemporary academic historiography. The reflection on different sorts of pasts that can be at focus in historical research and writing encompasses events as well as non-events, especially recursive social structures and cultural webs. Some consequences of such plurality for discussions concerning (...) historical methodology, explanation, exemplification, and representation are also outlined. The basic message, reinforced throughout, is that the great relevance of non-event-centred approaches should prompt us to talk more about “histories” in the plural and less about “history” in the singular. (shrink)

At the end of the 19th century, most professional historians – wherever they existed – deemed history to be a form of knowledge ruled by a method that bears no resemblance with those most commonly traceable in the natural sciences. The bulk of the historian’s task was then frequently regarded as being the application of procedures frequently referred to as ‘historical method’. In the context of such an emerging interest on historical methods and methodology, at least three textbooks stand out: (...) Johann Gustav Droysen’s Grundriss der Historik (Outline of the Theory of History), Ernst Bernheim’s Lehrbuch der historischen Methode (Handbook of Historical Method), and Charles Langlois and Charles Seignobos’s Introduction aux études historiques (Introduction to the Study of History). These books were quite influential in Germany, France, and elsewhere, and they very much helped promote a general idea of historical method that would become relatively consensual among historians of many nationalities by the early 20th century. Such a relative agreement on historical method sponsored both the communication and the development of a sense of disciplinary identity among historians trained within different and sometimes conflicting national traditions. It was then partially extended, partially challenged, and surely made more complex when, from the 1920s on, social and economic historians became a good part of the historiographical establishment in many countries. -/- The three books by Droysen, Bernheim, and Langlois and Seignobos were already pieced together by Rolf Torstendahl, who studied them as a group of texts that, despite their differences, contributed to shape the developments outlined above. However, Torstendahl’s primary aim was to show how Droysen, Bernheim, and Seignobos all resorted to ‘method’ as a way to circumvent skepticism against the possibility of historical knowledge, rather than investigate the internal interrelationships between the three texts. In this chapter I follow precisely this latter, not yet taken, road, focusing on crucial cross-references between the Grundriss, the Lehrbuch, and the Introduction. I intend to show that, at a general level, the schemes of historical method found in these texts are largely convergent, and that this convergence is due to Bernheim’s reading of Droysen and to Langlois and Seignobos’s reading of Bernheim. I will attempt to do it through a regressive approach that starts with an analysis of the Introduction. Aspects of the editorial history and circulation of the three texts will also be briefly addressed, as a way to illustrate their special importance within the framework of early 20th century historical theory. Because my argument calls for a focus on the most general lines of Droysen’s, Bernheim’s, and Langlois and Seignobos’s schemes of historical method, I will, for the sake of consistency, refrain from analysing in-depth the complex epistemological and ontological arguments in which those schemes are nested. (shrink)