Recreational Drugs European Network (ReDNet) project aims to use the Psychonaut Web Mapping Project database (Psychonaut Web Mapping Group, 2009) containing novel psychoactive compounds usually not mentioned in the scientific literature and thus unknown to clinicians as a unique source of information. The database will be used to develop an integrated ICT prevention approach targeted at vulnerable individuals and focused on novel synthetic and herbal compounds and combinations. Particular care will be taken in keeping the health professionals working directly with (...) young people showing problematic behaviors regularly updated in terms of novel compounds and combinations as well. A user-friendly project website will be developed aimed primarily at delivering the information/prevention approaches, but will also be a way of communicating with project partners and relevant stakeholders (e.g. thematic forum facilities, instant messages, blogs, video chat, wikiblog, newsletters distributed via mailing list). The website will support various ICT prevention tools, including an SMS alert service. Different areas and sections will be aimed specifically at the different target groups. -/- . (shrink)

In real-time, Twitter strongly imprints world events, popular culture, and the day-to-day; Twitter records an ever growing compendium of language use and change; and Twitter has been shown to enable certain kinds of prediction. Vitally, and absent from many standard corpora such as books and news archives, Twitter also encodes popularity and spreading through retweets. Here, we describe Storywrangler, an ongoing, day-scale curation of over 100 billion tweets containing around 1 trillion 1-grams from 2008 to 2020. For each day, we (...) break tweets into 1-, 2-, and 3-grams across 150+ languages, record usage frequencies, and generate Zipf distributions. We make the data set available through an interactive time series viewer, and as downloadable time series and daily distributions. We showcase a few examples of the many possible avenues of study we aim to enable including how social amplification can be visualized through ‘contagiograms’. (shrink)

'A Differential Play of Forces' is a study of transcendental empiricism in musical contexts. It presents a reading of Gilles Deleuze and Félix Guattari’s philosophical apparatus and explores how music can be thought of as functioning in the operation Deleuze terms transcendental empiricism. Central to transcendental empiricism is the idea of an encounter with intensive difference and the consequent experience of intensive and virtual forces. The thesis sets out to explore this idea in three interwoven steps. First, it develops transcendental (...) empiricism as a philosophical framework, expounding central notions related to time and aesthetic experience. In the context of this philosophical apparatus, music is then discussed as an encounter with intensity and what this may entail for our understanding of musical experience and its potential. The third part of the thesis explores the idea of experiencing intensive forces through music in the thinking and poietic of three composers of the twentieth century: Arnold Schönberg, Olivier Messiaen and Giacinto Scelsi. The thesis develops three ‘images of thought’ corresponding, respectively, to the composers’ expressed theoretical ideas, identifying central concepts from Deleuze and Guattari’s philosophy. A mutual illumination of ideas about music and transcendental empiricism is thus presented, pointing towards a possible convergence between theory and practice, thinking and aesthetic experience as a differential play of intensive forces. (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)

What It’s Like to Chill Out With Whom the Rest of the World Considers As The Most Ruthless Men: Ratko Mladic, Goran Hadzic and Radovan Karadzic (+) Confessions of a Female War Crimes Investigator By Jill Louise Starr NJ USA -/- Read My Entire Book Here (True Story) http://sites.google.com/site/thelawprojectscenternycoffices/what-it-s-like-to-chill-out-with-whom-th e-rest-of-the-world-considers-as-the-most-ruthless-men-ratko-mladic-goran-hadzic-and-radovan-karadzi c-confessions-of-a-female-war-crimes-investigator -/- Retrospectively, it was all so simple, natural and matter of fact being on a boat restaurant in Belgrade, sitting with, laughing, drinking a two hundred bottle of wine and chatting about (...) war and peace while Ratko Mladic held my hand. Mladic, a man considered the world’s most ruthless war criminal since Adolf Hitler, still at large and currently having a five million dollar bounty on his head for genocide by the international community. Yet there I was with my two best friends at the time, a former Serbian diplomat, his wife, and Ratko Mladic just chilling. There was no security, nothing you’d ordinarily expect in such circumstances. Referring to himself merely as, Sharko; this is the story of it all came about. Diplomatic / International Relations Consultant & War Crimes Investigator - War - Peace - Preventive Diplomatic Strategies - International Law - Charitable Causes - International Business - International Political Economy - Human Rights - Politics - War Crimes Investigations - Anti-Terrorism - Law Projects Center Funded Projects (YCICC) Internationally LPCYU Home Website -/- Irrefutable Proof ICTY Is Corrupt Court/Irrefutable Proof the Hague Court Cannot Legitimately Prosecute Karadzic Case By Jill Starr I want to stress, in this particular meeting , there was no observer status at the ICC Preparatory Meetings at the United Nations in New York City in 2001. What I did, made a historical precedent. I was asked by, Darko Trifunovic 1st Secretary of the Bosnian MIssion, to take his place, in a CLOSED DOOR UNITED NATIONS MEETING. This means, ONLY HEADS OF AMBASSADORIAL MISSIONS WERE ALLOWED IN THE MEETING. There was no "Observer Status for say NGO's such as Amnesty International." I represented a Country as an American Citizen that day; the Repuklika Srpska. This never occurred before to my knowledge ever. It was an error. My former professor, Arnold Stark, walked me in, A former State Dept. man chosen to be the former Ambassador from the USA to Bonn/Germany (and he declined years back because of his wife at the time). He knew it was illegal. It said on these paper I picked up in the meeting, Anyone, Richard Holbrooke, sat across from me, discussing this meeting outside the meeting itself thereafter , "would be prosecuted to the fullest extent of int'l law." I heard the Ambassadors of the world ALL DISCUS TRADING MONEY FOR ICC AND ICTY COURT VERDICT AS WELL AS FUTURE JUDICIAL APPOINTMENTS -/- http://sites.google.com/site/thelawprojectscenternycoffices/home/irrefutable-proof-icty-is-corrupt-c ourt-irrefutable-proof-the-hague-court-cannot-legitimately-prosecute-karadzic-case -/- http://picasaweb.google.com/lpcyusa/IrrefutableProofICTYIsCorruptCourtIrrefutabl# (The Documentary Secret United Nations ICC Meeting Papers Scanned Images) OR http://community.jigsaw.com/t5/media/gallerypage/user-id/903610# -/- Rea dMore Here _> Read the entire story here My testimonial video on Youtube _> http://www.youtube.com/watch?v=dKe-5LORsGs -/- http://www.youtube.com/watch?v=dKe-5LORsGs (My YouTube VIDEO) -/- This legal technicality indicates the Hague must dismiss charges against Dr Karadzic and others awaiting trials in the Hague jail; like it or not. -/- Unfortunately for the Signatures Of the Rome Statute United Nations member states instituting the ICC & ICTY housed at the Hague, insofar as the, Radovan Karadzic, as with the other Hague cases awaiting trial there, I personally witnessed these United Nations member states having a substantial conversations, and, openly speaking about trading judicial appointments and verdicts for financial funding when I attended the 2001 ICC Preparatory Meetings at the UN in Manhattan making the iCTY and ICC morally incapable trying Radovan Karazdic and others. -/- I witnessed with my own eyes and ears when attending the 2001 Preparatory Meetings to establish an newly emergent International Criminal Court, the exact caliber of criminal corruption running so very deeply at the Hague, that it was a perfectly viable topic of legitimate conversation in those meetings I attended to debate trading verdicts AND judicial appointments, for monetary funding. -/- Jilly wrote:*The rep from Spain became distraught and when her country’s proposal was not taken to well by the chair of the meeting , then Spain argued in a particularly loud and noticably strongly vocal manner, “Spain (my country) strongly believes if we contribute most financial support to the Hague’s highest court, that ought to give us and other countries feeding it financially MORE direct power over its decisions.” -/- ((((((((((((((((((((((((( ((((((((((((((((((((((((( Instead of censoring the country representative from Spain for even bringing up this unjust, illegal and unfair judicial idea of bribery for international judicial verdicts and judicial appointments, all country representatives present in the meeting that day all treated the Spain proposition as a ”totally legitimate topic” discussed and debated it between each other for some time. I was quite shocked! The idea was “let’s discuss it.” "It’s a great topic to discuss." -/- Some countries agreed with Spain’s propositions while others did not. The point here is, bribery for judicial verdicts and judicial appointments was treated as a totally legitimate topic instead of an illegitimate topic which it is in the meeting that I attended in 2001 that day to establish the ground work for a newly emergent international criminal court.)))))))))))))))))))))))))))) -/- In particular., since “Spain” was so overtly unafraid in bringing up this topic of trading financial funding the ICC for influence over its future judicial appointments and verdicts in front of every other UN member state present that day at the UN, “Spain” must have already known by previous experience the topic of bribery was “socially acceptable” for conversation that day. They must have previously spoke about bribing the ICTY and ICC before in meetings; this is my take an international sociological honor student. -/- SPAIN’s diplomatic gesture of international justice insofar as, Serbia, in all of this is, disgusting morally!SPAIN HAS TAUGHT THE WORLD THE TRUE DEFINITION OF AN “INTERNATIONAL CRIMINAL COURT.” -/- I represented the state interests’ of the Former Yugoslavia, in Diplomat Darko Trifunovic’s absence in those meetings and I am proud to undertake this effort on Serbia’s behalf. http://picasaweb.google.com/lpcyusa (My Political Satire Blog) Diplomatic / International Relations Consultant & War Crimes Investigator - War - Peace - Preventive Diplomatic Strategies - International Law - Charitable Causes - International Business - International Political Economy - Human Rights - Politics - War Crimes Investigations - Anti-Terrorism - Law Projects Center Funded Projects (YCICC) Internationally http://sites.google.com/site/jillstarrsite -/- -/- . 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What would it be for a process to happen backwards in time? Would such a process involve different causal relations? It is common to understand the time-reversal invariance of a physical theory in causal terms, such that whatever can happen forwards in time can also happen backwards in time. This has led many to hold that time-reversal symmetry is incompatible with the asymmetry of cause and effect. This article critiques the causal reading of time reversal. First, I argue that the (...) causal reading requires time-reversal-related models to be understood as representing distinct possible worlds and, on such a reading, causal relations are compatible with time-reversal symmetry. Second, I argue that the former approach does, however, raise serious sceptical problems regarding the causal relations of paradigm causal processes and as a consequence there are overwhelming reasons to prefer a non-causal reading of time reversal, whereby time reversal leaves causal relations invariant. On the non-causal reading, time-reversal symmetry poses no significant conceptual nor epistemological problems for causation. _1_ Introduction _1.1_ The directionality argument _1.2_ Time reversal _2_ What Does Time Reversal Reverse? _2.1_ The B- and C-theory of time _2.2_ Time reversal on the C-theory _2.3_ Answers _3_ Does Time Reversal Reverse Causal Relations? _3.1_ Causation, billiards, and snooker _3.2_ The epistemology of causal direction _3.3_ Answers _4_ Is Time-Reversal Symmetry Compatible with Causation? _4.1_ Incompatibilism _4.2_ Compatibilism _4.3_ Answers _5_ Outlook. (shrink)

Bertrand Russell famously argued that causation is not part of the fundamental physical description of the world, describing the notion of cause as “a relic of a bygone age”. This paper assesses one of Russell’s arguments for this conclusion: the ‘Directionality Argument’, which holds that the time symmetry of fundamental physics is inconsistent with the time asymmetry of causation. We claim that the coherence and success of the Directionality Argument crucially depends on the proper interpretation of the ‘ time symmetry’ (...) of fundamental physics as it appears in the argument, and offer two alternative interpretations. We argue that: if ‘ time symmetry’ is understood as the time -reversal invariance of physical theories, then the crucial premise of the Directionality Argument should be rejected; and if ‘ time symmetry’ is understood as the temporally bidirectional nomic dependence relations of physical laws, then the crucial premise of the Directionality Argument is far more plausible. We defend the second reading as continuous with Russell’s writings, and consider the consequences of the bidirectionality of nomic dependence relations in physics for the metaphysics of causation. (shrink)

Experiences of motion and change are widely taken to have a ‘flow-like’ quality. Call this ‘temporal qualia’. Temporal qualia are commonly thought to be central to the question of whether time objectively passes: (1) passage realists take temporal passage to be necessary in order for us to have the temporal qualia we do; (2) passage antirealists typically concede that time appears to pass, as though our temporal qualia falsely represent time as passing. I reject both claims and make the case (...) that passage-talk plays no useful explanatory role with respect to temporal qualia, but rather obfuscates what the philosophical problem of temporal qualia is. I offer a ‘reductionist’ account of temporal qualia that makes no reference to the concept of passage and argue that it is well motivated by empirical studies in motion perception. (shrink)

This paper assesses branching spacetime theories in light of metaphysical considerations concerning time. I present the A, B, and C series in terms of the temporal structure they impose on sets of events, and raise problems for two elements of extant branching spacetime theories—McCall’s ‘branch attrition’, and the ‘no backward branching’ feature of Belnap’s ‘branching space-time’—in terms of their respective A- and B-theoretic nature. I argue that McCall’s presentation of branch attrition can only be coherently formulated on a model with (...) at least two temporal dimensions, and that this results in severing the link between branch attrition and the flow of time. I argue that ‘no backward branching’ prohibits Belnap’s theory from capturing the modal content of indeterministic physical theories, and results in it ascribing to the world a time-asymmetric modal structure that lacks physical justification. (shrink)

In questo contributo del 2008 si dimostra, attraverso un confronto con le posizioni di Max Scheler, che Alsberg con il disimpegno corporeo (Körperausschaltung) non mira a esonerare l’organismo (nel senso della Entlastung di Gehlen). Per Alsberg l’evoluzione sociale avviene attraverso utensili, ma l’utensile non si limita a essere un’appendice del corpo, bensì rappresenta una logica estranea a quella del corpo. La Körperausschaltung è il killer del corpo. L’errore di Spencer è quello di non comprendere che un’evoluzione basata su utensili non (...) è semplicemente “sovra-organica”, ma piuttosto “extraorganica”. Extra-organico per Alsberg significa che l’utensile è al di fuori della logica del corpo. Ed è proprio l’autonomia dell’utensile dalla biologia a permettere di risolvere il paradosso della duplicità costitutiva dell’uomo: l’essere il motore di un’evoluzione extra-organica che produce contemporaneamente involuzione organica. Il “disimpegno organico” che libera l’uomo dal bisogno è possibile solo perché il problema dell’adattamento e dell’evoluzione viene spostato sul piano extra-organico: tale spostamento è ciò che contraddistingue l’uomo da tutti gli altri esseri viventi, quindi il principio costitutivo dell’esser umano. L' Ausschaltung, come disattivazione del corpo (dal verbo tedesco auschalten, nel senso di spegnere, ad es. una macchina, la luce ecc.) diventa pertanto il principio ultimo per comprendere l'umano nella sua interezza e non solo l'uomo della modernità (l'homo faber). L'eccezionale testo di Alsberg rimarrà praticamente sconosciuto, tuttavia con eccezioni di rilievo: già negli anni '20 ha un impatto decisivo su Max Scheler e sul progetto di fondazione dell'antropologia filosofica. Successivamente, ma con esiti opposti, su Gehlen. Il concetto di Körperausschaltung viene ripreso anche da Dieter Claessens, da Hans Blumenberg e infine da Sloterdijk. (shrink)

In what sense is the direction of time a matter of convention? In 'The Direction of Time', Hans Reichenbach makes brief reference to parallels between his views about the status of time’s direction and his conventionalism about geometry. In this article, I: (1) provide a conventionalist account of time direction motivated by a number of Reichenbach’s claims in the book; (2) show how forwards and backwards time can give equivalent descriptions of the world despite the former being the ‘natural’ direction (...) of time; and (3) argue that this offers an important middle-ground position between existing realist and antirealist accounts of the direction of time. (shrink)

“The universe is expanding, not contracting.” Many statements of this form appear unambiguously true; after all, the discovery of the universe’s expansion is one of the great triumphs of empirical science. However, the statement is time-directed: the universe expands towards what we call the future; it contracts towards the past. If we deny that time has a direction, should we also deny that the universe is really expanding? This article draws together and discusses what I call ‘C-theories’ of time — (...) in short, philosophical positions that hold time lacks a direction — from different areas of the literature. I set out the various motivations, aims, and problems for C-theories, and outline different versions of antirealism about the direction of time. (shrink)

Modern physics has provided a range of motivations for holding time to be fundamentally undirected. But how does a temporally adirectional metaphysics, or ‘C-theory’ of time, fit with the time of experience? In this chapter, I look at what kind of problem human time poses for C-theories. First, I ask whether there is a ‘hard problem’ of human time: whether it is in principle impossible to have the kinds of experience we do in a temporally adirectional world. Second I consider (...) the ‘easy problem’: how specific directed aspects of our temporal experience are to be explained by C-theorists. This leads to a greater issue: is there such a thing as an experience of time direction at all to even be explained? I show how the kinds of experience we have that we typically associate with the idea of time being directed can be accommodated within a directionless picture of time. (shrink)

It is often said that the world is explained by laws of nature together with initial conditions. But does that mean initial conditions don’t require further explanation? And does the explanatory role played by initial conditions entail or require that time has a preferred direction? This chapter looks at the use of the ‘initialness defence’ in physics, the idea that initial conditions are intrinsically special in that they don’t require further explanation, unlike the state of the world at other times. (...) Such defences commonly assume a primitive directionality of time to distinguish between initial and final conditions. Using the case study of the time-asymmetry of thermodynamics and the so-called ‘past hypothesis’ — the hypothesis that the early universe was in a state of very low entropy —, I outline and support a deflationary account of the initialness defence that does not pre- suppose a basic directionality of time, and argue that there is a relevant explanatory asymmetry between initial conditions and the state of systems at other times only if certain causal conditions are satisfied. Hence, the initialness defence is available to those who reject a fundamental direction of time. (shrink)

In the two feature articles for this volume, Gruber et al and Buonomano & Rovelli focus on what the former call the 'two-times problem', in short, the apparent lack of fit between time as described by physical science and our own temporal experience, where 'experience' involves things like memory, anticipation, and perception of change and motion. In this short note I'll make the case that the twotimes problem is less serious than it is often made out to be in the (...) specific case of features like 'passage ' and 'presentness' that are central to the 'A-theory' of time ---the theory that holds time to be composed of dynamic regions of 'past', 'present' and future', and for time to genuinely flow or pass.My contention is three-fold: (1) the two-times problem is better understood as a three-times problem: rather than a conflict between 'physical' and 'manifest' time, what we have in the case of time is differences between the time of physics, the time of experience, and the 'folk' concept of time. (2) Understanding the problem in this way helps deflate certain problems about the relationship of these three pictures; the time of experience and the time of physics are less obviously in a problematic conflict than often supposed; and the folk concept of time is what brings in problematic features of time hard to fit with either the time of physics of experience. (3) Understanding the time of experience as independent from the folk concept of time better fits the actual aims of the... (shrink)

Imagine that you and a duplicate of yourself are lying unconscious, next to each other, about to undergo a complete step-by-step exchange of bits of your bodies. It certainly seems that at no stage in this exchange of bits will you have thereby switched places with your duplicate. Yet it also seems that the end-result, with all the bits exchanged, will be essentially that of the two of you having switched places. Where will you awaken? I claim that one and (...) the same person possesses both bodies, occupies both places and will experience both awakenings, just as a person whose brain has been bisected must at once experience both of the unconnected fields of awareness, even though each of these will falsely appear to him as the entirety of his experience. I also claim that the more usual apparent boundaries of persons are as illusory as those in brain bisection; personal identity remains unchanged through any variation or multiplication of body or mind. In all conscious life there is only one person - I - whose existence depends merely on the presence of a quality that is inherent in all experience - its quality of being mine, the simple immediacy of it for whatever is having experience. One powerful argument for this is statistical: on the ordinary view of personhood it is an incredible coincidence for you (though not for others) that out of 200,000,000 sperm cells the very one required on each occasion for your future existence was first to the egg in each of the begettings of yourself and all your ancestors. The only view that does not make your existence incredible, and that is not therefore (from your perspective) an incredible view, is that any conscious being would necessarily have been you anyway. It is a consequence that self-interest should extend to all conscious organisms. (shrink)

Strawson's view on punishment has been either neglected or recoiled from in contemporary scholarship on ‘Freedom and Resentment’ (FR). Strawson's alleged retributivism has made his view suspect and troublesome. In this article, we first argue, against the mainstream, that the punishment passage is an indispensable part of the main argument in FR (section 1) and elucidate in what sense Strawson can be called ‘a retributivist’ (section 2). We then elaborate our own hypothesis of symbolic retribution to explain the continuum between (...) moral reactive attitudes and punishment that Strawson only adumbrates (section 3). After this justification of the punitive response to wrongdoing, we compare and contrast our specific kind of retributivist hypothesis with other positions in the so-called ‘new retributivism’ (section 4). Our hypothesis differs from other subvarieties of expressive retributivism in putting centre stage the idea of punishment as taking up a reverential stance towards the victim. (shrink)

Cognitive science has recently made some startling discoveries about temporal experience, and these discoveries have been drafted into philosophical service. We survey recent appeals to cognitive science in the philosophical debate over whether time objectively passes. Since this research is currently in its infancy, we identify some directions for future research.

The Pessimistic Induction over the history of science argues that because most past theories considered empirically successful in their time turn out to be not even approximately true, most present ones probably aren’t approximately true either. But why did past scientists accept those incorrect theories? Kyle Stanford’s ‘Problem of Unconceived Alternatives’ is one answer to that question: scientists are bad at exhausting the space of plausible hypotheses to explain the evidence available to them. Here, I offer another answer, which I (...) call the ‘Problem of Misleading Evidence.’ I argue that this proposal is, in important respects, superior to Stanford’s. (shrink)

Since anonymous agents can spread misinformation with impunity, many people advocate for greater accountability for internet speech. This paper provides a veritistic argument that accountability mechanisms can cause significant epistemic problems for internet encyclopedias and social media communities. I show that accountability mechanisms can undermine both the dissemination of true beliefs and the detection of error. Drawing on social psychology and behavioral economics, I suggest alternative mechanisms for increasing the trustworthiness of internet communication.

In a recent Philosophy of Science article Gerhard Schurz proposes meta-inductivistic prediction strategies as a new approach to Hume's. This comment examines the limitations of Schurz's approach. It can be proven that the meta-inductivist approach does not work any more if the meta-inductivists have to face an infinite number of alternative predictors. With his limitation it remains doubtful whether the meta-inductivist can provide a full solution to the problem of induction.

While Thomas Kuhn's theory of scientific revolutions does not specifically deal with validation, the validation of simulations can be related in various ways to Kuhn's theory: 1) Computer simulations are sometimes depicted as located between experiments and theoretical reasoning, thus potentially blurring the line between theory and empirical research. Does this require a new kind of research logic that is different from the classical paradigm which clearly distinguishes between theory and empirical observation? I argue that this is not the case. (...) 2) Another typical feature of computer simulations is their being ``motley'' (Winsberg 2003) with respect to the various premises that enter into simulations. A possible consequence is that in case of failure it can become difficult to tell which of the premises is to blame. Could this issue be understood as fostering Kuhn's mild relativism with respect to theory choice? I argue that there is no need to worry about relativism with respect to computer simulations, in particular. 3) The field of social simulations, in particular, still lacks a common understanding concerning the requirements of empirical validation of simulations. Does this mean that social simulations are still in a pre-scientific state in the sense of Kuhn? My conclusion is that despite ongoing efforts to promote quality standards in this field, lack of proper validation is still a problem of many published simulation studies and that, at least large parts of social simulations must be considered as pre-scientific. (shrink)

Human beings define their identity primarily by the way they present, design and style their bodies. In doing so, individuals make statements about their affiliation to a social context. Globalisation implies a change of identity among the members of less industrialised cultures, as they are exposed to effects of cultural dominance. For the individual, this exposure can be the stronger, the more autonomous his or her culture of origin used to be before the confrontation. There is a bias of cultural (...) elements that are being transferred, so that the industrialised culture has a strong impact on other cultures. Global consent with regard to behaviour patterns, especially to bodily self-presentation and the related cognitive styles, leads to the obliteration of traditional knowledge, which is interwoven with the behaviour upon which identity had been defined previously. The cultural elements transferred are being used for the construction of globally standardised personal identities, whereat elements concerning the visual design of the human body are of major relevance for defining the self. The loss of variegated identities in favour of belonging to the global society brings about a number of problems, which can be demonstrated in functional models. These models, in turn, may support the planning of interventional strategies and rescue work. In this article, the role of the body within the destabilising effects of cultural change are analysed, and chances for intervention are discussed. (shrink)

Confused terms appear to signify more than one entity. Carnap maintained that any putative name that is associated with more than one object in a relevant universe of discourse fails to be a genuine name. Although many philosophers have agreed with Carnap, they have not always agreed among themselves about the truth-values of atomic sentences containing such terms. Some hold that such atomic sentences are always false, and others claim they are always truth-valueless. Field maintained that confused terms can still (...) refer, albeit partially, and offered a supervaluational account of their semantic properties on which some atomic sentences with confused terms can be true. After outlining many of the most important theoretical considerations for and against various semantic theories for such terms, we report the results of a study designed to investigate which of these accounts best accords with the truth-value judgments of ordinary language users about sentences containing these terms. We found that naïve participants view confused names as capable of successfully referring to one or more objects. Thus, semantic theories that judge them to involve total reference failure do not comport well with patterns of ordinary usage. (shrink)

The underdetermination of theory by data obtains when, inescapably, evidence is insufficient to allow scientists to decide responsibly between rival theories. One response to would-be underdetermination is to deny that the rival theories are distinct theories at all, insisting instead that they are just different formulations of the same underlying theory; we call this the identical rivals response. An argument adapted from John Norton suggests that the response is presumptively always appropriate, while another from Larry Laudan and Jarrett Leplin suggests (...) that the response is never appropriate. Arguments from Einstein for the special and general theories of relativity may fruitfully be seen as instances of the identical rivals response; since Einstein’s arguments are generally accepted, the response is at least sometimes appropriate. But when is it appropriate? We attempt to steer a middle course between Norton’s view and that of Laudan and Leplin: the identical rivals response is appropriate when there is good reason for adopting a parsimonious ontology. Although in simple cases the identical rivals response need not involve any ontological difference between the theories, in actual scientific cases it typically requires treating apparent posits of the various theories as mere verbal ornaments or computational conveniences. Since these would-be posits are not now detectable, there is no perfectly reliable way to decide whether we should eliminate them or not. As such, there is no rule for deciding whether the identical rivals response is appropriate or not. Nevertheless, there are considerations that suggest for and against the response; we conclude by suggesting two of them. (shrink)

This paper proposes a radical re-examination of the foundations of modern aesthetics. It urges that we replace the tradition of eighteenth century aesthetics, with its insistence on disinterestedness and the separateness of the aesthetic, and its problematic oppositions, such as the separation of sense from cognition. In their place it appeals to a more process-oriented, pluralistic account, one that takes note of varying cultural traditions in aesthetics, that recognizes the aesthetic as a complex of many forces and factors, and that (...) considers the aesthetic as part of a complexity of values, including moral, practical, social, and political ones. It urges, further, an aesthetic-based criticism, not only of the arts, but of culture and knowledge. Central to this account is the idea of aesthetic engagement, which not only recognizes and extends the many connections of and in aesthetic experience, but invites our total involvement as active participants. (shrink)

Scientific anti-realists who appeal to the pessimistic induction (PI) claim that the theoretical terms of past scientific theories often fail to refer to anything. But on standard views in philosophy of language, such reference failures prima facie lead to certain sentences being neither true nor false. Thus, if these standard views are correct, then the conclusion of the PI should be that significant chunks of current theories are truth-valueless. But that is semantic anti-realism about scientific discourse—a position most philosophers of (...) science, anti-realists included, consider anathema today. Therefore, proponents of the PI confront a dilemma: either accept semantic anti-realism or reject common semantic views. I examine strategies (with particular emphasis on supervaluations) for the PI proponent to either lessen the sting of this argument, or learn to live with it. 1 Introduction2 Designation Failure 2.1 Designation failure leads to truth-valueless sentences2.1.1 Direct reference theory2.1.2 Fregeanism2.1.3 Accounts of reference-fixing: why ‘phlogiston’ fails to designate 2.2 Objection: sentences exhibiting designation failure are false not truth-valueless 2.3 Avoiding truth-valuelessness via controversial semantic positions3 What to do? Closing the Gaps4 Conclusion. (shrink)

This paper discusses critically what simulation models of the evolution of cooperation can possibly prove by examining Axelrod’s “Evolution of Cooperation” (1984) and the modeling tradition it has inspired. Hardly any of the many simulation models in this tradition have been applicable empirically. Axelrod’s role model suggested a research design that seemingly allowed to draw general conclusions from simulation models even if the mechanisms that drive the simulation could not be identified empirically. But this research design was fundamentally flawed. At (...) best such simulations can claim to prove logical possibilities, i.e. they prove that certain phenomena are possible as the consequence of the modeling assumptions built into the simulation, but not that they are possible or can be expected to occur in reality. I suggest several requirements under which proofs of logical possibilities can nevertheless be considered useful. Sadly, most Axelrod-style simulations do not meet these requirements. It would be better not to use this kind of simulations at all. (shrink)

My visual cortex at the back of my brain processes the stimulation to my eyes and then causes other parts of the brain - like the speech centre and the areas involved in thought and movement - to be properly responsive to vision. According to functionalism the whole mental character of vision - the whole of how things look - is fixed purely in the pattern of responses to vision and not in any of the initial processing of vision in (...) the visual cortex. That this functionalist theory of vision is true can be proved with alarming ease. Imagine that just the left side of my visual cortex is replaced by a gadget that has precisely the same input/output relationship to the rest of the brain as the left visual cortex had. According to any view but functionalism, the character of my vision on the right side of my visual field (normally processed by the left visual cortex) would change radically with this change in all the intrinsic properties involved in the visual cortex, with this preservation of nothing but its functional role in bringing about my responses to vision. But, say I, we have enough here to be sure that in such a case there could be no change in the character of my vision. For we know by the stipulation of sameness of output that my responses in speech, thought and movement to the right side of my visual field will be precisely the same as they would have been with the natural left visual cortex and will harmonise just as they would have done with my responses to the other side of my vision. But if half my vision had disappeared or changed I’d be speaking, thinking and acting like someone with problems on the right side of his vision. It is impossible to separate my responses to vision from the character of my vision. The character of my vision is logically determined by the pattern of responses - by nothing but the functional role of my vision. (shrink)

This paper examines the critique of Voegelin in Kelsens "Secular Religion". While Kelsen sets out with the false premise that secular world view can in principle have no religious character, his critique of Voegelin remains largely unimpaired by this mistake. With convincing arguments Kelsen criticises (1) Voegelins interpretation of modernity as an age of gnosticism, (2) Voegelins reinterpretation of enlightened and secular philosopher as gnostics in disguise and (3) Voegelins rejection of modern politics and, to a lesser degree, modern science. (...) I have also uploaded the critical margin notes that some person (unfortunately I do not know any more who) had been so friendly to sent me. The paper was originally written in German, but an English translation is available as well. (shrink)

Degas, Manet, Picasso, Dali and Lipchitz produced works of art exemplifying a seeming impossibility: Not only combining incompatible attributes but doing so consistently with aesthetic strictures Horace formulated in Ars Poetica. The article explains how these artists were able to do this, achieving what some critics have called ‘a new art,’ ‘a miracle,’ and ‘a new metaphor.’ The article also argues that the author achieved the same result in sculpture by means of philosophical analysis – probably a first in the (...) history of art. (shrink)

Employing computer simulations for the study of the evolution of altruism has been popular since Axelrod's book "The Evolution of Cooperation". But have the myriads of simulation studies that followed in Axelrod's footsteps really increased our knowledge about the evolution of altruism or cooperation? This book examines in detail the working mechanisms of simulation based evolutionary explanations of altruism. It shows that the "theoretical insights" that can be derived from simulation studies are often quite arbitrary and of little use for (...) the empirical research. In the final chapter of the book, therefore, a set of epistemological requirements for computer simulations is proposed and recommendations for the proper research design of simulation studies are made. (shrink)

To investigate cultural lifestyle preferences in different cultural contexts, a forced-choice questionnaire was constructed, based on Thurstone's Law of Comparative Judgement, an almost forgotten statistical method of 1927, which is a useful tool for assessing groups. This study's questionnaire items targeted job and living conditions in the spectrum from traditional to globalised lifestyles. Subjects were indigenous representatives at the UNO in Geneva, and students in Nigeria, Cameroon, South Africa and Germany. The preferences ascertained reflect attitudes on a scale ranging from (...) very traditional to very globalised lifestyles. Although being an uncommon assessment tool, Thurstone's Comparative Judgement indicates to yield highly valid outcomes, as the results of the African university students, though from three different countries, resembled each other, but were complementary to the results of the indigenous representatives, which, in turn, mirrored the Berlin controls' profiles, according to expectations. Findings are discussed in light of the Symbolic Self-Completion Theory. (shrink)

The Aesthetic Field develops an account of aesthetic experience that distinguishes four mutually interacting factors: the creative factor represented primarily by the artist; the appreciative one by the viewer, listener, or reader; the objective factor by the art object, which is the focus of the experience; and the performative by the activator of the aesthetic occurrence. Each of these factors both affects all the others and is in turn influenced by them, so none can be adequately considered apart from them. (...) Thus aesthetic appreciation, for example, has creative, objective, and performative aspects. This situation of four factors, together with social, cultural, technological, and historical influences on them, is called the aesthetic field. Although the factors are theoretically distinguishable, they are experienced as a unity. It is important, therefore, not to confound the theoretical explanation of aesthetic experience with the experience, itself. The aesthetic field has important implications for understanding the various individual arts, new developments in the arts, and the critical appraisal of the arts. Moreover, the concept transforms traditional issues in aesthetics. (shrink)

Coronavirus disease 2019 can lead to respiratory failure. Some patients require extracorporeal membrane oxygenation support. During the current pandemic, health care resources in some cities have been overwhelmed, and doctors have faced complex decisions about resource allocation. We present a case in which a pediatric hospital caring for both children and adults seeks to establish guidelines for the use of extracorporeal membrane oxygenation if there are not enough resources to treat every patient. Experts in critical care, end-of-life care, bioethics, and (...) health policy discuss if age should guide rationing decisions. (shrink)

W.V.O. Quine has famously objected that (1) properties are philosophically suspect because (2) there is no entity without identity and (3) the synonymy criterion for property identity won't do because there's no such concept as synonymy. (2) and (3) may or may not be right but do not prove (1). I reply that Leiniz's Law handles property identity, as it does for everything else, then respond to a variety of objections and confusions.

Many commentators on Alfred Tarski have, following Hartry Field, claimed that Tarski's truth-definition was motivated by physicalism—the doctrine that all facts, including semantic facts, must be reducible to physical facts. I claim, instead, that Tarski did not aim to reduce semantic facts to physical ones. Thus, Field's criticism that Tarski's truth-definition fails to fulfill physicalist ambitions does not reveal Tarski to be inconsistent, since Tarski's goal is not to vindicate physicalism. I argue that Tarski's only published remarks that speak approvingly (...) of physicalism were written in unusual circumstances: Tarski was likely attempting to appease an audience of physicalists that he viewed as hostile to his ideas. In later sections I develop positive accounts of: (1) Tarski's reduction of semantic concepts; (2) Tarski's motivation to develop formal semantics in the particular way he does; and (3) the role physicalism plays in Tarski's thought. (shrink)

I argue that a certain type of naturalist should not accept a prominent version of the no-miracles argument (NMA). First, scientists (usually) do not accept explanations whose explanans-statements neither generate novel predictions nor unify apparently disparate established claims. Second, scientific realism (as it appears in the NMA) is an explanans that makes no new predictions and fails to unify disparate established claims. Third, many proponents of the NMA explicitly adopt a naturalism that forbids philosophy of science from using any methods (...) not employed by science itself. Therefore, such naturalistic philosophers of science should not accept the version of scientific realism that appears in the NMA. (shrink)

In the progress of globalisation, the human being is exposed to effects of cultural dominance. For the individual, this exposure can be the stronger, the more autonomous his or her culture of origin used to be before the confrontation. Global consent with regard to behaviour patterns and cogni¬tive styles leads to the obliteration of traditional knowledge and behaviour upon which identity has been defined. The loss of identity in favour of belonging to the global society brings about a number of (...) problems, which can be demonstrated in functional models. These models, in turn, may sup¬port the planning of interventional strategies and rescue work. (shrink)

This article presents a paradox of inclusion, like Russell’s paradox but in a natural language.

This paper tries to answer the question why the epistemic value of so many social simulations is questionable. I consider the epistemic value of a social simulation as questionable if it contributes neither directly nor indirectly to the understanding of empirical reality. To examine this question, two classical social simulations are analyzed with respect to their possible epistemic justification: Schelling’s neighborhood segregation model and Axelrod’s reiterated Prisoner’s Dilemma simulations of the evolution of cooperation. It is argued that Schelling’s simulation is (...) useful because it can be related to empirical reality, while Axelrod’s simulations and those of his followers cannot and thus that their scientific value remains doubtful. I relate this findingto the background beliefs of modelers about the superiority of the modeling method as expressed in Joshua Epstein’s keynote address “Why model?”. (shrink)

Definitions I presented in a previous article as part of a semantic approach in epistemology assumed that the concept of derivability from standard logic held across all mathematical and scientific disciplines. The present article argues that this assumption is not true for quantum mechanics (QM) by showing that concepts of validity applicable to proofs in mathematics and in classical mechanics are inapplicable to proofs in QM. Because semantic epistemology must include this important theory, revision is necessary. The one I propose (...) also extends semantic epistemology beyond the ‘hard’ sciences. The article ends by presenting and then refuting some responses QM theorists might make to my arguments. (shrink)

Suppose one believes that the historical record of discarded scientific theories provides good evidence against scientific realism. Should one adopt Kyle Stanford’s specific version of this view, based on the Problem of Unconceived Alternatives? I present reasons for answering this question in the negative. In particular, Stanford’s challenge cannot use many of the prima facie strongest pieces of historical evidence against realism, namely: superseded theories whose successors were explicitly conceived, and superseded theories that were not the result of elimination-of-alternatives inferences. (...) Attempts to accommodate and within Stanford’s framework are incompatible with other commitments Stanford holds, such as anti-realism being piecemeal instead of global. As separate lines of criticism, I argue that there are problems with Stanford’s claim that the PUA is the most important challenge to realism, and with his view of instrumentalist theory endorsement. (shrink)

Many have tackled the question ‘What (if anything) is analytic philosophy?’ I will not attempt to answer this vexed question. Rather, I address a smaller, more manageable set of interrelated questions: first, when and how did people begin using the label ‘analytic philosophy’? Second, how did those who used this label understand it? Third, why did many philosophers we today classify as analytic initially resist being grouped together under the single category of ‘analytic philosophy’? Finally, for the first generation who (...) described themselves as analytic philosophers, what was their intended contrast class? Relatedly, when did ‘continental philosophy’ become the standard opposition? Some evidence I present justifies received answers to these questions; other evidence supports surprising and unorthodox answers to these questions. (shrink)

An epistemology of art has seemed problematic mainly because of arguments claiming that an essential element of a theory of knowledge, truth, has no place in aesthetic contexts. For, if it is objectively true that something is beautiful, it seems to follow that the predicate “is beautiful” expresses a property – a view asserted by Plato but denied by Hume and Kant. But then, if the belief that something is beautiful is not objectively true, we cannot be said to know (...) that something is beautiful and the path to an epistemology of art is effectively blocked. The article places the existence aesthetic properties in the proper context; presents a logically correct argument for the existence of such properties; identifies strategies for responding to this argument; explains why objections by Hume, Kant, and several other philosophers fail; and sketches a realization account of beauty influenced by Hogarth. (shrink)

En 2007, la Declaración sobre los Derechos de los Pueblos Indígenas fue adoptada por la Asamblea General con la mayoría de los estados miembros de las Naciones Unidas. La declaración tiene relevancia para cualquiera que esté al mando o en contacto con los pueblos indígenas. Un efecto central de la dominancia de la cultura globalizada sobre culturas indígenas es la asimetría de la percepción e influencia mutua. Debido a los efectos de la presión social externa de la globalización los pueblos (...) indígenas tienen poca libertad de elección. Ejercer su derecho a una autonomía cultural en educación y estilo de vida es muy difícil para los indígenas. Por parte de gobiernos, problemas con los derechos sobre la tierra son un obstáculo para reconocer la autonomía de los pueblos indígenas. Algunos artículos de la declaración de derechos indígenas son presentados que tienen relevancia para personas externas, como investigadores o turistas, en contacto con personas indígenas. -/- The Declaration on the Rights of Indigenous peoples is an instrument to combat inequalities on an international level. However, the implementation is still a matter of disregard and conflict, as states are reluctant to give up their privileges. Yet, with the Declaration, a foundation has been laid to claim acceptance and respect of indigenous lifestyles, the use of their territories by themselves, the passing-on of culturally specific knowledge to the next generations, and other aspects. The new situation of International Law also brought along consequences for any external person contacting an indigenous culture, be it scientists, tourists or others. (shrink)

This paper is intended as a critical examination of the question of when and under what conditions the use of computer simulations is beneficial to scientific explanations. This objective is pursued in two steps: First, I try to establish clear criteria that simulations must meet in order to be explanatory. Basically, a simulation has explanatory power only if it includes all causally relevant factors of a given empirical configuration and if the simulation delivers stable results within the measurement inaccuracies of (...) the input parameters. -/- In the second step, I examine a few examples of Axelrod-style simulations as they have been used to understand the evolution of cooperation (Axelrod, Schüßler). These simulations do not meet the criteria for explanatory validity and it can be shown, as I believe, that they lead us astray from the scientific problems they have been addressed to solve. (shrink)

Simulation models of the Reiterated Prisoner's Dilemma (in the following: RPD-models) are since 30 years considered as one of the standard tools to study the evolution of cooperation (Rangoni 2013; Hoffmann 2000). A considerable number of such simulation models has been produced by scientists. Unfortunately, though, none of these models has empirically been verified and there exists no example of empirical research where any of the RPD-models has successfully been employed to a particular instance of cooperation. Surprisingly, this has not (...) kept scientists from continuing to produce simulation models in the same tradition and from writing their own history as a history of success. In a recent simulation study -- which does not make use of the RPD but otherwise follows the same pattern of research -- Robert Axelrod's (1984) original role model for this kind of simulation studies is praised as ``an extremely effective means for investigating the evolution of cooperation'' and considered as ``widely credited with invigorating that field'' (Rendell et al. 2010). (shrink)