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)

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)

The aim of this study was to explore the existence of moral distress among nurses in Lilongwe District of Malawi. Qualitative research was conducted in selected health institutions of Lilongwe District in Malawi to assess knowledge and causes of moral distress among nurses and coping mechanisms and sources of support that are used by morally distressed nurses. Data were collected from a purposive sample of 20 nurses through in-depth interviews using a semi-structured interview guide. Thematic analysis of qualitative data was (...) used. The results show that nurses, irrespective of age, work experience and tribe, experienced moral distress related to patient/nursing care. The major distressing factors were inadequate resources and lack of respect from patients, guardians, peers and bosses. Nurses desire teamwork and ethics committees in their health institutions as a means of controlling and preventing moral distress. There is a need for creation of awareness for nurses to recognize and manage moral distress, thus optimizing their ability to provide quality and uncompromised nursing care. (shrink)

Because corporate social responsibility can be beneficial to both companies and its stakeholders, interest in factors that support CSR performance has grown in recent years. A thorough integration of CSR in core business processes is particularly important for achieving effective long-term CSR practices. Here, we explored the individual CSR-related competencies that support CSR implementation in a corporate context. First, a systematic literature review was performed in which relevant scientific articles were identified and analyzed. Next, 28 CSR directors and managers were (...) interviewed. The literature review complemented with interview data resulted in the following eight distinct CSR-related competencies: Anticipating CSR challenges; Understanding CSR-relevant systems and subsystems; Understanding CSR-relevant standards; CSR management competencies, including Leading CSR programs, Managing CSR programs, and Identifying and realizing CSR-related business opportunities; Realizing CSR-supportive interpersonal processes; Employing CSR-supportive personal characteristics and attitudes; Personal value-driven competencies, including Ethical normative competencies, Balancing personal ethical values and business objectives, and Realizing self-regulated CSR-related behaviors and active involvement; and Reflecting on personal CSR views and experiences. Based on these results, implications for further research on this topic, as well as implications for practitioners, are discussed. (shrink)

R&D collaborations between industry, government, civil society, and research ) have recently gained attention from R&D theorists and practitioners. In aiming to come to grips with their complexity, past models have generally taken a stakeholder-analytical approach based on stakeholder types. Yet stakeholder types are difficult to operationalise. We therefore argue that a processual model is more suited for studying the interaction in QHCs because it eschews matters of titles and identities. We develop such a model in which the QHC is (...) represented as a process of generating four types of value: research value, market value, political value, and societal value. We then apply this processual model in analysing real-life cases of friction in QHCs. Friction is seen, not as an interpersonal clash, but as a discrepancy between two or more value-creation processes that compete for limited resources. (shrink)

The objectives of the study are to determine the main trends and characteristics of the provision of services by Ukrainian travel companies over the past 10 years. Ukraine is explored in terms of domestic and international tourism (inbound and outbound). The study uses the data of the World Tourism Organization (UNWTO), the State Statistics Service of Ukraine, the data of the regional statistical offices, as well as the results of the author's calculations. Modern methods of global clustering and marketing segmentation, (...) using statistically significant data of quantitative and qualitative expert assessments, allow us to identify the development trend of the service of Ukrainian travel agencies. Завдання дослідження - визначення основних тенденції і характерних особливостей надання послуг українськими туристичними компаніями за останні 10 років. Досліджується Україна в розрізі внутрішнього та міжнародного туризму (в'їзного та виїзного). У дослідженні використовуються дані Всесвітньої організації туризму, Державної служби статистики України, дані регіональних управлінь статистики, а також результати авторських розрахунків. Сучасні методи глобальної кластеризації і маркетингової сегментації, з використанням статистично значущих даних кількісних і якісних експертних оцінок, дозволяють ідентифікувати тренд розвитку сервісу українських туристичних компаній. (shrink)

In abstract algebraic logic, many systems, such as those paraconsistent logics taking inspiration from da Costa's hierarchy, are not algebraizable by even the broadest standard methodologies, as that of Blok and Pigozzi. However, these logics can be semantically characterized by means of non-deterministic algebraic structures such as Nmatrices, RNmatrices and swap structures. These structures are based on multialgebras, which generalize algebras by allowing the result of an operation to assume a non-empty set of values. This leads to an interest in (...) exploring the foundations of multialgebras applied to the study of logic systems. -/- It is well known from universal algebra that, for every signature Sigma, there exist algebras over Sigma which are absolutely free, meaning that they do not satisfy any identities or, alternatively, satisfy the universal mapping property for the class of Sigma-algebras. Furthermore, once we fix a cardinality of the generating set, they are, up to isomorphisms, unique, and equal to algebras of terms (or propositional formulas, in the context of logic). Equivalently, the forgetful functor, from the category of Sigma-algebras to Set, has a left adjoint. This result does not extend to multialgebras. Not only multialgebras satisfying the universal mapping property do not exist, but the forgetful functor U, from the category of Sigma-multialgebras to Set, does not have a left adjoint. -/- In this paper we generalize, in a natural way, algebras of terms to multialgebras of terms, whose family of submultialgebras enjoys many properties of the former. One example is that, to every pair consisting of a function, from a submultialgebra of a multialgebra of terms to another multialgebra, and a collection of choices (which selects how a homomorphism approaches indeterminacies), there corresponds a unique homomorphism, what resembles the universal mapping property. Another example is that the multialgebras of terms are generated by a set that may be viewed as a strong basis, which we call the ground of the multialgebra. Submultialgebras of multialgebras of terms are what we call weakly free multialgebras. Finally, with these definitions at hand, we offer a simple proof that multialgebras with the universal mapping property for the class of all multialgebras do not exist and that U does not have a left adjoint. (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)

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)

This article is part of a For-Discussion-Section of Methods of Information in Medicine about the paper "Biomedical Informatics: We Are What We Publish", written by Peter L. Elkin, Steven H. Brown, and Graham Wright. It is introduced by an editorial. This article contains the combined commentaries invited to independently comment on the Elkin et al. paper. In subsequent issues the discussion can continue through letters to the editor.

These arguments prove the necessity of developing highly competitive effective innovation strategy of the national economy aimed at developing modern innovative system that ensures the competitiveness of the national economy through effective use of scientific and technological capabilities towards promoting good economic growth.

As schools publicly modernize in response to societal changes, additional teaching and learning methods are developed, observed, and used since learners have different learning styles that make it easier for them to grasp and retain the material. During the COVID-19 pandemic, teachers require different media to keep the classroom involved while presenting the lesson materials online, one of which is video tutorials. The purpose of this study was to analyze the extent of contextual effects of video tutorials used in general (...) chemistry, determine the relationship between video tutorial effectiveness and the respondents' academic performance, and analyze the significant difference between the four indicators of contextual effects of video tutorials and the respondents' profile. A descriptive-correlational quantitative research design was used in this study. The participants in this study were 144 Grade 12 STEM students from a private school in Sultan Kudarat, Philippines, who took their general chemistry course during the pandemic. The respondents were given a survey questionnaire created with Google Forms. The students agreed with all the assertions and rated them as effective in terms of their perceptions of general chemistry, implying that video tutorials are useful in teaching the subject. With p-values of .023, .046, and .010, respectively, the findings revealed a significant relationship between the overall mean of students' perceptions of the subject of General Chemistry, the concept and application of chemical knowledge and understanding, and their influence on students' academic performance. In terms of their perception, ideas, and application of chemical knowledge and comprehension, the results demonstrated that there is no statistically significant difference between the general mean of male and female students' responses. This basically means that by using video lectures, STEM students of all genders appreciate and understand General Chemistry as a subject. -/- . (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.

Graduates' employability indicates the excellent education and relevant preparation they obtained from their respective degrees. Tracer studies have enabled higher education institutions to profile their graduates while also reflecting on the quality of education they provide. With the foregoing, a tracer study determined the demographic and academic profile of teacher education graduates from 2017 to 2020 in a state university in the West Philippines. It also ascertained the advanced studies they attended after college, their employment data, the relevance of college (...) preparation with their current employment, difficulties they encountered while securing employment and in their present job, and recommendations to strengthen the teacher education program. The study utilized a descriptive survey research design with 80 non-random samples chosen based on availability. The survey was based on the Philippine Commission on Higher Education with modifications elucidated from previous studies. Results showed that graduates took the teacher education program with a strong passion for the teaching profession. More graduates received honors and awards, passed the licensure examinations for teachers, attended advanced studies for professional development, and are employable. Besides, the graduates’ college preparation is relevant to their current employment. Further, difficulties and problems encountered and recommendations to strengthen the teacher education program were noted. These findings may serve as a baseline for curriculum review and give suggestions for future tracer studies. (shrink)

This paper discusses critically what simulation models of the evolution ofcooperation can possibly prove by examining Axelrod’s “Evolution of Cooperation” and the modeling tradition it has inspired. Hardly any of the many simulation models of the evolution of cooperation 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, because it is not possible to draw general empirical conclusions from theoretical simulations. 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. I contrast this with Schelling’s neighborhood segregation model, thecore mechanism of which can be retraced empirically. (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)

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)

In 2035 global egg demand will have risen 50% from 1985. Because we are not able to tell in the egg whether it will become a male or female chick, billons of one day-old male chicks will be killed. International research initiatives are underway in this area, and governments encourage the development of an alternative with the goal of eliminating the culling of day-old male chicks. The Netherlands holds an exceptional position in the European egg trade, but is also the (...) only country in the European Union where the downside of the egg sector, the practice of killing day-old male chicks, is a recurrent subject of societal debate. ‘Preventing the killing of young animals’ and ‘in ovo sex determination’ are the two alternative approaches available to solve this problem. It is clear that both approaches solve the problem of killing day-old male chicks, either by keeping them alive or by preventing them from living, but they also raise a lot of new animal welfare-related dilemmas. A thorough analysis was undertaken of these dilemmas and the results are presented in this article. The analysis resulted in an ethical framework based on the two main approaches in bioethics: a consequentialist approach and a deontological approach. This ethical framework was used to develop an online survey administered to ascertain Dutch public opinion about these alternative approaches. The results show that neither alternative will be fully accepted, or accepted by more than half of Dutch society. However, the survey does provide an insight into the motives that are important for people’s choice: food safety and a good treatment of animals. Irrespective of the approach chosen, these values should be safeguarded and communicated clearly. (shrink)

The aim of this paper is to provide a conceptual framework that will help in understanding and evaluating, along social and ethical lines, the issue of killing day-old male chicks and two alternative directions of responsible innovations to solve this issue. The following research questions are addressed: Why is the killing of day-old chicks morally problematic? Are the proposed alternatives morally sound? To what extent do the alternatives lead to responsible innovation? The conceptual framework demonstrates clearly that there is a (...) moral “lock-in”, and why the killing of day-old chicks is indeed an issue. Furthermore, it is shown that both alternative directions address some important objections with regard to the killing of day-old chicks, but that they also raise new dilemmas. It also becomes clear that the framework enables and secures anticipation, reflection, deliberation with and responsiveness to stakeholders, the four dimensions of responsible innovation, in a structured way. (shrink)

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

Cải cách tiền lương là một trong những nội dung quan trọng sẽ được thảo luận tại Kỳ họp thứ 6, Quốc hội khóa XV và đây cũng là một trong những chìa khoá để mở ra các chính sách đãi ngộ nhằm góp phần xây dựng, phát triển đội ngũ trí thức nước nhà, đáp ứng yêu cầu phát triển đất nước nhanh và bền vững trong giai đoạn mới như nội dung mà Hội nghị Trung ương 8 khoá (...) XIII, Ban Chấp hành Trung ương Đảng đã thảo luận. (shrink)

Purpose Prescription stimulant use as “cognitive enhancers” has been described among undergraduate college students. However, the use of prescription stimulants among future health care professionals is not well characterized. This study was designed to determine the prevalence of prescription stimulant misuse among students at an academic health sciences center. -/- Method Electronic surveys were e-mailed to 621 medical, pharmacy, and respiratory therapy students at East Tennessee State University for four consecutive weeks in fall 2011. Completing the survey was voluntary and (...) anonymous. Surveys asked about reasons for, frequency of, and side effects of nonprescription misuse of prescription stimulants. Given the sensitive material, an opportunity to win one of ten $50 gift cards was used as an incentive. -/- Results Three hundred seventy-two (59.9%) students completed the survey from three disciplines (47.6% medical, 70.5% pharmacy, and 57.6% respiratory therapy). Overall, 11.3% of responders admitted to misusing prescription stimulants. There was more misuse by respiratory therapy students, although this was not statistically significant (10.9% medicine, 9.7% pharmacy, 26.3% respiratory therapy; P = .087). Reasons for prescription stimulant misuse included to enhance alertness/ energy (65.9%), to improve academic performance (56.7%), to experiment (18.2%), and to use recreationally/get high (4.5%). -/- Conclusions Prescription stimulant misuse was prevalent among participating students, but further research is needed to describe prevalence among future health care workers more generally. The implications and consequences of such misuse require further study across professions with emphasis on investigating issues of academic dishonesty (e.g., “cognitive enhancement”), educational quality, and patient safety or health care quality. (shrink)

This paper addresses the issues related to designing and estimating the strength of solid-alloy elements in the deforming broaches of significant diameter (exceeding 150 mm) for the developed process of discrete broaching. The tool limit condition was assessed based on two strength criteria: the specific potential energy of shape change and the maximum tangent stresses. Numerical modeling using the finite element method has made it possible to derive the distribution of equivalent stresses in the tool elements and the contact stresses (...) at the surface of the contact between a solid-alloy insert and the body, which enabled the analysis of tool strength under loading. The simulation was performed under a single normal load, which ensured the versatility of the calculation for any contact pressure values. We have derived formulae to calculate the acceptable contact pressure depending on unit load. The effect of the insert protrusion height over the body on the strength of tool elements has been established. We have derived engineering dependences that determine the required magnitude of insert protrusion over the body depending on the ultimate load. An example of calculating the strength of a prefabricated deforming element in the machining of a sleeve made from gray modified cast iron of hardness HB230 has been considered. Our calculations have shown that the deforming element designed for the new technological process corresponds to the conditions of strength, provided the ratio h1/h=0.15 is maintained (where h1 is the insert height above the body, h is the insert height). The results obtained could be used in engineering calculations when designing the prefabricated tool for discrete deformation, as well as to assess the strength of prefabricated tools, such as cutters, core drills, reamers, when refining external loads. (shrink)

Purpose. To determine the potential of deforming broaching for the improvement of efficiency of cutter chisels in the mining industry. Methodology. The study of the application of the technological process of deforming broaching was carried out based on the experimental research into conditions of assembly of press couplings corresponding to cutting rock-destroying tools, the working surface of which is reinforced with solid-alloy inserts. Findings. Based on the conducted research, a new process of assembling the crowns of cutter chisels with the (...) use of deforming broaching was developed. Originality. It was determined that the range of angles of inclination of generatrix of the working cone of the deforming element and the roll-treading lip of the insert, which are necessary for efficient machining and pressing in crowns of cutters, is 4–16°. It was proven that the “solid alloy-steel” press couplings for cutter chisels will have the maximum bearing capacity at total tension a/d0 ≤ 3 %. It was found that it is necessary to foresee the following distribution of tensions: to perform 2 % of deformation by preliminary deforming broaching, and 1 % ‒ by pressing in an insert Practical value. The use of deforming broaching makes it possible to increase the strength of fastening the inserts of cutter chisels by 2 times, to reduce specific consumption of the tool by 4.4 times, and to increase the average drilling rate by 4 times. (shrink)

This is a series of lectures on formal decision theory held at the University of Bayreuth during the summer terms 2008 and 2009. It largely follows the book from Michael D. Resnik: Choices. An Introduction to Decision Theory, 5th ed. Minneapolis London 2000 and covers the topics: -/- Decisions under ignorance and risk Probability calculus (Kolmogoroff Axioms, Bayes' Theorem) Philosophical interpretations of probability (R. v. Mises, Ramsey-De Finetti) Neuman-Morgenstern Utility Theory Introductory Game Theory Social Choice Theory (Sen's Paradox of Liberalism, (...) Arrow's Theorem) . (shrink)

New trends in the economic systems management in the context of modern global challenges: collective monograph / scientific edited by M. Bezpartochnyi, in 2 Vol. // VUZF University of Finance, Business and Entrepreneurship. – Sofia: VUZF Publishing House “St. Grigorii Bogoslov”, 2020. – Vol. 1. – 309 p.

This study investigated the effectiveness of utilizing induced magnetism on the seed germination of radish (Raphanussativus) in terms of growth rate, growth speed, shoot growth, and overall development. This study utilized two groups that consisted of an experimental group where induced magnetism was present one control group where there was an absence of induced magnetism in the seed germination of Radish (Raphanus sativus). Moreover, this study aimed to determine the significant difference between the two in terms growth rate, growth speed, (...) shoot growth, and overall development. Both groups had the same amount of radish (Raphanus sativus) seeds planted in a rectangular wooden container with the same amount of measurement and soil content. This study used an experimental research design by utilizing the functions of an Electromagnetic Induction Device (EID) comprised of a 12v motor battery, light bulb, coiled wire, and switch. The EID was turned on for 10 minutes every day where the electric volts generated by the 12v motor battery were transported through the coiled wire and distributed to the metallic iron screen surrounding the area of the experimental group. The data gathered during the 12-day observation of the growth of radish (Raphanus sativus) were tabulated, analyzed, and evaluated using mean tests, standard deviation, and T-test. Based on the result and analyses of the gathered data, it was found that the experimental group, the one with the presence of induced magnetism, surpassed the control group in terms of growth speed, shoot growth, and overall seed development. However, it was also revealed that in terms of growth rate, there is no significant difference between the control group and experimental group. Therefore, the utilization of Induced Magnetism on the seed germination of radish (Raphanus sativus) is effective in terms of growth speed, shoot growth, and overall development. (shrink)

Purpose of the present work is to attempt to give a glance at the problem of existential and anthropological risk caused by the contemporary man-made civilization from the perspective of comparison and confrontation of aesthetics, the substrate of which is emotional and metaphorical interpretation of individual subjective values and politics feeding by objectively rational interests of social groups. In both cases there is some semantic gap present between the represented social reality and its representation in perception of works of art (...) and in the political doctrines as well. Methodology of the research is evolutionary anthropologicalcomparativistics. Originality of the conducted analysis comes to the following: As the antithesis to biological and social reductionism in interpretation of the phenomenon of bio-power it is proposed a co-evolutionary semantic model in accordance with which the described semantic gap is of the substantial nature related to the complex module organization of a consistent and adaptive human strategy consisting of three associated but independently functional modules. Evolutionary trajectory of all anthropogenesis components including civilization cultural and social-political evolution is identified by the proportion between two macro variables – evolutionary effectiveness and evolutionary stability, i.e. preservation in the context of consequential transformations of some invariants of Homo sapiens species specificity organization. It should be noted that inasmuch as in respect to human, some modules of the evolutionary strategy assume self-reflection attributes, it would be more correctly to state about evolutionary correctness, i.e. correspondence to some perfection. As a result, the future of human nature depends not only on the rationalist principles of ethics of Homo species, but also on the holistic and emotionally aesthetic image of «Self». In conclusion it should be noted that there is a causal link between the development of High Hume technologies and the totality of the trend in the anthropological phenomenon of bio-power that permeates all the available human existence in modern civilization. As a result, there is a transformation of a contemporary social risk in the evolutionary civilization risk. (shrink)

The humanity is examined on two levels: first as a natural biological quality having a moral dimension and a moral impact, and then as a moral quality, which is a specific human product and a result of cultural evolution, i.e. of human moral deve-lopment. According to the forms of the realized humanity the author differentiates between active and passive forms of humanity; the active humanity is further divided into a positive and a negative ones.

Resumo: Neste texto, introduzo algumas questões importantes que fazem parte do debate sobre infiltração pragmática. Além de apresentar e problematizar as principais alegações oferecidas pelos proponentes da infiltração pragmática eu irei contrasta-la com algumas teses mais tradicionais, como a Tese Tradicional sobre o Conhecimento e o Contextualismo Epistêmico. Por fim, apresento uma crítica aos proponentes da infiltração pragmática que parece ainda não ter sido tratada. Concluo que embora controversa, tal tese está longe de ser refutada completamente. Palavras-chave: Conhecimento; Contexto; Justificação; (...) Padrões; Infiltração prática. -/- Abstract: In this paper I introduce some central aspects concerning the debate on pragmatic encroachment. After introducing and discussing the main arguments offered by the pragmatic encroachers advocates I will contrast it with more traditional theses such as the Traditional Analysis of Knowledge and Epistemic Contextualism. Finally, I present an objection to the pragmatic encroachment approach that haven't been treated yet. I conclude that despite its difficulties, the pragmatic encroachment view is far from being refuted. Keywords: Knowledge; Context; Justification; Standards; Pragmatic encroachment. (shrink)

Letters commenting on Hardwig, J "Is There a Duty to Die?" with a reply to those letters by the author.

In the author’s view the humanity has its place in the ethics of social consequences : its implementation leads directly to positive social consequences, i.e. the main evaluation criteria in this conception. However, in applying the principle of humanity one has to see humanity as the protection of sustainable life according to the degree, to which an individual human life meets at least minimal qualitative standards of human life. The resulting idea is that a person living only on the biological (...) level should be let die. This is not an expression of non-humanity, as it is not in case of helping a dying person with fatal diagnosis in his ever increasing suffering. As the problem of war is concerned, according to the author no war is human, as it always brings about dying of innocent people. (shrink)

The paper explores the theory of right action in ethics of social consequences as a form of non-utilitarian consequentialism.

Purpose (metatask) of the present work is to attempt to give a glance at the problem of existential and anthropo- logical risk caused by the contemporary man-made civilization from the perspective of comparison and confronta- tion of aesthetics, the substrate of which is emotional and metaphorical interpretation of individual subjective values and politics feeding by objectively rational interests of social groups. In both cases there is some semantic gap pre- sent between the represented social reality and its representation in perception (...) of works of art and in the political doctrines as well. Methodology of the research is evolutionary anthropological comparativistics. Originality of the conducted analysis comes to the following: As the antithesis to biological and social reductionism in interpretation of the phenomenon of bio-power it is proposed a co-evolutionary semantic model in accordance with which the de- scribed semantic gap is of the substantial nature related to the complex module organization of a consistent and adaptive human strategy consisting of three associated but independently functional modules (genetic, cultural and techno-rational). Evolutionary trajectory of all anthropogenesis components including civilization cultural and so- cial-political evolution is identified by the proportion between two macro variables – evolutionary effectiveness and evolutionary stability (sameness), i.e. preservation in the context of consequential transformations of some invari- ants of Homo sapiens species specificity organization. It should be noted that inasmuch as in respect to human, some modules of the evolutionary (adaptive) strategy assume self-reflection attributes, it would be more correctly to state about evolutionary correctness, i.e. correspondence to some perfection. As a result, the future of human nature de- pends not only on the rationalist principles of ethics of Homo species (the archaism of Jurgen Habermas), but also on the holistic and emotionally aesthetic image of «Self». In conclusion it should be noted that there is a causal link between the development of High Hume (NBIC) technologies and the totality of the trend in the anthropological phenomenon of bio-power that permeates all the available human existence in modern civilization. As a result, there is a transformation of a contemporary social (man-made) risk in the evolutionary civilization risk. (shrink)

Az "alkalmazott filozofia" egy uj korvonalazasa ugy a modszertan mint a tematikak szompontjabol.

Is consistency the sort of thing that could provide a guide to mathematical ontology? If so, which notion of consistency suits this purpose? Mark Balaguer holds such a view in the context of platonism, the view that mathematical objects are non-causal, non-spatiotemporal, and non-mental. For the purposes of this paper, we will examine several notions of consistency with respect to how they can provide a platon-ist epistemology of mathematics. Only a Gödelian notion, we suggest, can provide a satisfactory guide to (...) a platonist ontology. Is consistency the sort of thing that could provide a guide to mathematical ontology? If so, which notion of consistency suits this purpose? Mark Bala-guer holds such a view in the context of platonism, the view that mathematical objects are non-causal, non-spatiotemporal, and non-mental. Balaguer's version of Platonism, Full-Blooded Platonism (FBP), is the view that "there are as many abstract mathematical objects as there could be-i.e., there actually exist abstract mathematical objects of all possible kinds" (Balaguer, 2017, p. 381). He continues: Since FBP says that there are abstract mathematical objects of all possible kinds, it follows that if FBP is true, then every purely mathematical theory that could be true-i.e., that is internally consistent-accurately describes some collection of actually existing abstract objects. Thus it follows from FBP that in order to acquire knowledge of abstract objects, all we have to do is come up with an internally consistent purely mathematical theory (and know that it is internally consistent). (Balaguer, 2017, p. 381) * To be published in 43rd International Wittgenstein Symposium proceedings. (shrink)

Edited proceedings of an interdisciplinary symposium on consciousness held at the University of Cambridge in January 1978. Includes a foreword by Freeman Dyson. Chapter authors: G. Vesey, R.L. Gregory, H.C. Longuet-Higgins, N.K. Humphrey, H.B. Barlow, D.M. MacKay, B.D. Josephson, M. Roth, V.S. Ramachandran, S. Padfield, and (editorial summary only) E. Noakes. A scanned pdf is available from this web site (philpapers.org), while alternative versions more suitable for copying text are available from https://www.repository.cam.ac.uk/handle/1810/245189. -/- Page numbering convention for the pdf version (...) viewed in a pdf viewer is as follows: 'go to page n' accesses the pair of scanned pages 2n and 2n+1. Applicable licence: CC Attribution-NonCommercial-ShareAlike 2.0. (shrink)

Purpose of this article is to investigate the role that the "miraculous" – that is, everything that goes beyond “natural” – plays in the worldview of Western man. Methodology. I do not consider “miracles” as the facts of nature, but as the facts of culture, so in this article I am not talking about specific cases of violation of “laws of nature”, but about the place of “miraculous” in the view of the world of Western man and those transformations, that (...) occur with this element outlook influenced the development of information technologies. Novelty. It has been proved that miracles should be sought in mind, because the “miraculous” event does our attitude towards it. Moreover, it is impossible to determine the “true miracle”, while we are “inside” the reality. It has been demonstrated that influenced the development of society is transformed representations of gods and miracles. It has been discovered fundamental shift associated with the transition from mythology-as-faith to mythology-as-show. However, even within the latter remains a need for miracles, though, and goes to a completely different level. Conclusions. The term "miracle" has no meaning outside of accepted socio-cultural settings. The last set as the “natural” conditions and admissibility (inadmissibility) of its violation. And these installations are formed by social institutions, which in this age and at this time have a weight sufficient to impose their views to all the congregation or the greater part. Any extraordinary event can be explained by the action of internal agents unknown to us, and their ability to alter the reality is not necessarily superior to even our own capabilities. The only thing we can not do – is to change the source code of being (e.g., fundamental physical constants). This could make only creatures that are not spelled out in these source codes. However, people have not seen anything like it, and scarcely become witnesses of such events. (shrink)

This dissertation concerns the methodology Kant employs in the first two sections of the Groundwork of the Metaphysics of Morals (Groundwork I-II) with particular attention to how the execution of the method of analysis in these sections contributes to the establishment of moral metaphysics as a science. My thesis is that Kant had a detailed strategy for the Groundwork, that this strategy and Kant’s reasons for adopting it can be ascertained from the Critique of Pure Reason (first Critique) and his (...) lectures on logic, and that understanding this strategy gains us interpretive insight into Kant’s moral metaphysics. At the most general level of methodology, Kant says there are four steps for the establishment of any science: 1) make distinct the idea of the natural unity of its material 2) determine the special content of the science 3) articulate the systematic unity of the science 4) critique the science to determine its boundaries The first two of these steps are accomplished by the genetically scholastic method of analysis, paradigmatically the method whereby confused and obscure ideas are made clear and distinct, thereby logically perfecting them and transforming them into possible grounds of cognitive insight that are potentially complete and adequate to philosophical purposes. The analysis of Groundwork I is a paradigmatic analysis that makes distinct what is contained in common understanding, i.e. its Inhalt or intension, making distinct the higher partial concepts that together define the concept of morality. The analysis of Groundwork II is an employment more specifically of the method of logical division, which makes distinct what is contained under the concept, i.e. its Umfang, by which the extension or object of morality is determined. Part I introduces Kant’s conception of moral metaphysical science and why he took it to be in need of establishment, explains the general method for establishing science and the scholastic method of analysis by which its first two steps are to be accomplished, then provides an interpretation of Groundwork I as an execution of this method. Part II details Kant’s determination of the special content of moral science in Groundwork II in relation to the central problem for moral metaphysics – how synthetic a priori practical cognition is possible. (shrink)

Digital technologies are becoming an essential tool in modern trade, contributing to its development and change. This article examines global trends in using digital technologies in trade and their potential impact on the Ukrainian market. The research shows that e-commerce, mobile shopping experience, smart technologies, and data analytics are key areas that affect consumers and business processes. The authors of the article analyze the impact of digital technologies on consumers, pointing to the growth of e-commerce and the convenience of online (...) shopping. Smart technologies such as facial recognition, chatbots, and virtual reality are becoming increasingly common in trade processes. The authors discuss the potential benefits of digital technologies for the Ukrainian market and point out the need to adapt and implement these innovations. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Reviewed by:The Cambridge Companion to OckhamJeffrey E. BrowerPaul Vincent Spade, editor. The Cambridge Companion to Ockham. Cambridge: Cambridge University Press, 1999. Pp. xii + 400. Cloth, $54.95.Contemporary analytic philosophers have always been among the most enthusiastic audiences for the volumes in the Cambridge Companion series. And of all the great philosophers of the Middle Ages, perhaps none has appealed more to their sensibilities than William Ockham. It is fitting, (...) therefore, that after the publication of the Companion to Aquinas—the first volume in the series devoted to a medieval philosopher—there should appear a Companion to Ockham.The fifteen chapters comprising this volume survey the entire range of Ockham's thought and may conveniently be divided into four main parts. The first part (chaps. 2-7) deals with Ockham's most enduring legacy: his contribution to issues falling within the domain of logic, philosophy of language, and metaphysics. The second part (chaps. 8-9) is devoted to issues in epistemology and philosophy of mind/cognition. The third part (chaps. 10-13) focuses on Ockham's views in ethics, action theory, and political philosophy. And the fourth part (chaps. 14-15) considers aspects of his philosophical theology. In addition, there is also an historical chapter (chap. 1), placing Ockham's life and works in their late-medieval intellectual context, and a brief editor's introduction, including a very useful list of all Ockham's writings, together with the best (sometimes, the only) Latin editions and English translations available.The volume is well organized and beautifully conceived. Some chapters are quite difficult, and in places contain material that is likely to be unfamiliar even to specialists in medieval philosophy. But the way in which they have been organized maximizes their usefulness and accessibility to specialists and non-specialists alike. The earlier parts of the volume lay the foundation for later ones, and the individual chapters within each part are arranged so as to build on and complement one another. This is perhaps most evident in the five chapters comprising the first part. Calvin Normore's presentation ofOckham's logic (in chap. 2) nicely prepares the reader for Claude Panaccio's discussion (in chap. 3) of Ockham's theory of mental language. Panaccio's chapter, in turn, provides the framework for David Chalmer's analysis (in chap. 4) of the debate over whether [End Page 588] Ockham's mental language permits synonymous expressions. Again, these three chapters taken together provide important background for Paul Spade's treatment (in chap. 5) of Ockham's views in metaphysics, which are closely related to his logic and philosophy of language. Finally, Gyula Klima's discussion (in chap. 6) ofhow Ockham's views in semantics and ontology differ from those of his predecessors, and André Goddu's discussion (in chap. 7) of Ockham's philosophy of nature, can be fully appreciated only against the background of the preceding chapters.What is perhaps most impressive about the volume, however, is the extent to which it succeeds at providing a systematic introduction to Ockham's philosophical achievement. All the chapters are, to some extent, concerned with matters of textual analysis and interpretation. But most of them involve much more than a mere survey of Ockham's texts. For example, in each of the four main parts, there is at least one chapter that attempts to locate Ockham's views in relation to those of his predecessors or contemporaries (such as Aquinas and Scotus), with the result that we get a sense of Ockham's place in the major medieval debates to which he contributed. At the same time, the volume introduces us to some of the most lively current debates in Ockham scholarship. It does this, not merely by summarizing them, but by actually carrying them out over the course of its chapters. For example, Eleonore Stump provides a sophisticated defense (in chap. 8) of what has become a standard interpretation of Ockham's theory of intuitive and abstractive cognition. In the following chapter, however, Elizabeth Karger rejects the standard interpretation on the basis of a re-reading of certain key texts. Again, in the first part of the volume there is a running debate... (shrink)

*Runner-up for the 2021 Royal Institute for Philosophy Essay Prize*: What should we think about ‘acts of conscience’, viz., cases where our personal judgments and public authority come into conflict such that principled resistance to the latter seems necessary? Philosophers mainly debate two issues: the Accommodation Question, i.e., ‘When, if ever, should public authority accommodate claims of conscience?’ and the Justification Question, i.e., ‘When, if ever, are we justified in engaging in acts of conscience – and why?’. By contrast, a (...) third important topic – the Conduct Question, i.e., ‘How should we act, morally speaking, when engaging in acts of conscience?’ – has been mostly neglected. This paper aims to offer concrete guidance for persons wishing to engage in acts of conscience in morally virtuous ways. I argue that such agents are subject to two basic prima facie duties: duties to oneself related to demands of integrity and duties to others related to demands of civility. I explain both duties in detail, arguing with regard to, that in light of what I call ‘the paradox of conscience’, we need to rethink our views about both ‘conscience’ and ‘integrity’; and with regard to, that, building upon Rawls’ ‘duty of civility’, we should embrace at least seven general principles for undertaking acts of conscience in a morally conscientious manner. (shrink)

Đến khúc này, 3 ông bói cá cũng bí nên chuyển chủ đề. Hướng sang vấn đề ăn cá vậy. Đây là vấn đề truyền thống lâu đời. Có chuyện gì lớn?

From the rather original recognition that Aristotle’s categories are questions, this essay focuses on issues of the pote (ποτέ), i.e., the question of the “When”, and of chronos (χρόνος), the “concept” of time. This “concept” is born from and associated with the question of the “When”. It is a hermeneutical and (existential)-ontological dialogue, enabling us to think jointly about the so-called “objectivity” of time and its ontological, phenomenological, and hermeneutical relatedness to ourselves. The APPENDIX is an ontological and existential analysis (...) of the question: “What is man?”. It’s conclusion: that this question cannot, and indeed must not be given a definition-like answer, filled with information and facts. The “response” – and not “answer” – cor-responding to, can only be authentic and open if it claims that: Man is precisely that being who turns his own existence – in a questioning way, both for himself and “other” people, interrogating himself via his own world – into an event. The human and mode-of-being-like questions about the meaning of Being and about the possibility of “What is man?” actually overlap both in their horizons and in their amplitude and radicality. (shrink)

In this paper, I attempt to synthesize the two most influential contemporary ethical approaches that appeal to moral intuitions, viz., Rawlsian reflective equilibrium and Audi’s moderate intuitionism. This paper has two parts. First, building upon the work of Audi and Gaut, I provide a more detailed and nuanced account of how these two approaches are compatible. Second, I show how this novel synthesis can both (1) fully address the main objections to reflective equilibrium, viz., that it provides neither necessary nor (...) sufficient conditions for the justification of our moral beliefs and (2) help ethical intuitionism to deal with the fundamental problem of peer disagreement over our basic moral intuitions. In doing so, I sketch out a novel and attractive diachronic way of thinking about peer disagreement more generally. (shrink)

Os minerais possuem uma influência direta em diversos processos fisiológicos no organismo animal e, mesmo com tamanha importância, por vezes são negligenciados pelos produtores para seu fornecimento para os animais. Este estudo teve como objetivo avaliar o desempenho reprodutivo de rebanhos de bovinos, caprinos e ovinos em 8 propriedades rurais nas cidades de Sanharó, Pesqueira, Arcoverde, Belo Jardim e São Bento do Una através da adição de suplemento mineral e mistura múltipla aos animais de forma a atender suas necessidades básicas (...) para mantença e reprodução. Foram avaliados os desempenhos de 4 touros e 25 vacas, 3 bodes e 50 cabras e 4 carneiros e 48 ovelhas em diferentes propriedades, avaliando como a adição de um suplemento mineral específico da espécie impacta de forma positiva nos índices reprodutivos avaliados que foram taxa de cio, taxa de serviço, taxa de concepção, taxa de fertilidade, taxa de prenhez, taxa de perdas gestacionais, taxa de natalidade e taxa de mortalidade. O experimento teve duração de 2 anos e pôde-se avaliar cerca de 2 partos nas vacas e, mais ou menos, 3 partos em cabras e ovelhas. Os dados foram computados e avaliados estatisticamente no Excel para conferir se os índices reprodutivos melhoraram em função da adição de minerais na ração dos animais. Conferiu-se que houve diferença significativa entre todos os índices avaliados, ou seja, a adição de minerais na ração dos animais melhora a eficiência reprodutiva de machos e fêmeas de animais ruminantes, sendo de suma importância sua disponibilização de forma correta para alcançar bons índices reprodutivos na fazenda na busca pela obtenção de neonatos que poderão ser comercializados. -/- REFERÊNCIAS BIBLIOGRÁFICAS ASTRO, G. B. A importância da adição de minerais na dieta de caprinos e ovinos no Agreste de Pernambuco. Trabalho de Conclusão de Curso (Técnico Subsequente em Agropecuária) - IFPE Campus Belo Jardim. Belo Jardim, 2023. 44 p. BALAMURUGAN, B. et al. Mineral an important nutrient for efficient reproductive health in dairy cattle. Int. J. Environ. Sci. Technol, v. 6, n. 1, p. 694-701, 2017. Barros NN, Bomfim MAD. Mistura múltipla para caprinos e ovinos. In: Anais VIII PECNORDESTE – Seminário Nordestino de Pecuária, 8; 2004; Fortaleza, Brasil. Fortaleza: FAEC, 2004. p. 50-57. BERCHIELLI, T. T.; PIRES, A. V.; OLIVEIRA, S. G. (Eds.). Nutrição de ruminantes. Jaboticabal: Funep, 2011. COTTA, T. Minerais e vitaminas para bovinos, ovinos e caprinos. Viçosa: Aprenda Fácil, 2001. DANTAS, C. C. O.; DE MATTOS NEGRÃO, F. Funções e sintomas de deficiência dos minerais essenciais utilizados para suplementação dos bovinos de corte. UNICiências, v. 14, n. 2, 2010. DA SILVA EIC. A água na nutrição animal. 1ª ed. Recife, PE: Instituto Agronômico de Pernambuco, 2023. DA SILVA, Emanuel Isaque Cordeiro. Cálculos de consumo e digestibilidade de alimentos e nutrientes para ruminantes. Revista Universitária Brasileira, v. 1, n. 3, 2023. DA SILVA, Emanuel Isaque Cordeiro. Concentrados e Rações Para Cabras em Lactação. 2022. DA SILVA, Emanuel Isaque Cordeiro. Efeitos da raça e do manejo nutricional sobre as características de qualidade da carcaça e da carne em ovinos. Revista Universitária Brasileira, v. 2, n. 1, 2024. DA SILVA, Emanuel Isaque Cordeiro. 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Abstract: William Conklin takes on Hegel’s interpretation of Sophocles’ Antigone in this essay. Hegel asked what makes human laws human and what makes divine laws divine? After outlining Hegel’s interpretation of Antigone in the light of this issue, Conklin argues that we must address what makes human law law? and what makes divine law law? Taking his cue from Michel Foucault’s “What is an Author?”, the key to understanding Sophocles’ Antigone and Hegel’s interpretation to it, according to Conklin, is the (...) relationship between legal authority and an author. Antigone’s divine law opposes Creon’s human law in terms of whether the sense of legal authority presupposes an author. Antigone’s tribe recognises divine laws as nested in an impersonal Fate or Moira common to the Helenes as experienced through rituals and other personal experiences. Such an unwritten law lacks an author “whose origin we know not when”. The city-state’s citizens recognize authority in terms of whether a law has a source in a juridical representer of an invisible author. The invisible author is the city-state external to the representers. The representers interpret human laws in a manner which tries to access the invisible author. What becomes important is that philosophical consciousness observes how the characteristics of the two senses of legal authority clash. (shrink)

Introduction. Taking into account the priorities of the state policy in the field of economic and innovative development of the Perm region, assessment of the regional potential of the digital economy, the strategic importance of economic activities implemented by SMEs for the economy of the region and the country as a whole, the actual impact of the norms on the instruments of development of small and medium-sized enterprises in the Perm region is assessed. The purpose of this study is to (...) improve the regional regulatory platform of tools for the development of small and medium-sized businesses in the Perm region in order to gain the status of an investment-attractive region in the digital economy of the Russian Federation, taking into account the Strategy of the information society in the Russian Federation, which will ultimately contribute to the development of e-business in the Perm region, rehabilitation and competitiveness of the economy of the Perm region in the global market. Methodology. The General methodological basis of the study was the dialectical- materialistic method of cognition of legal reality, which allowed to study the tools of development of small and medium-sized businesses in the Perm region in their development, to consider the problems of tools for the integrated development of small and medium-sized businesses in the Perm region, taking into account the changed socio-economic conditions in inseparable unity with other related tools relevant to the needs of digitalization of society. Such universal scientific methods as analysis and synthesis of doctrinal and normative materials were used in the work. In addition, special legal methods were used: the method of legal modeling, which allows to design possible legal situations using digital tools for the development of small and medium- sized businesses in the Perm region; the method of systematic interpretation used in assessing the actual impact of regional norms on the tools of development of small and medium-sized businesses in the Perm region. Results. The article proposes a new tool for the development of SMEs as a regional electronic platform for the promotion of goods, works and services of SMEs in the Perm region. Attention is paid to the level of digital literacy of SMEs and consumers of their goods, works and services: the conclusion about the lack of digital competence. Conclusion. It is necessary to improve the regional regulatory platform taking into account economic trends: it is important to introduce digital competencies everywhere, including at the professional level in relation to SMEs in the Perm region, in order to increase the business activity of young people and other representatives of the working population. As for the actual introduction of new tools for the development of small and medium-sized businesses in the Perm region, we propose that the regional legislator develop a new electronic information platform at the expense of the regional budget to promote goods, works and services sold by SMEs in the Perm region. We believe that the measures proposed by us to enhance the economic activity of SMEs can be perceived by other regions. (shrink)

Contents Preface - ix -/- I. Scientific fiction movies: is there any place for God?! 1. A brief introduction about the birth of science fiction - 15 2. Religious beliefs vs Science Fiction - 18 3. Is there any place for God?! - 20 -/- II. The Village (M. Night Shyamalan) and The Giver (Phillip Noyce) or why utopia is (im)possible 1. Some utopian notions. Remembering Thomas More - 29 2. The Village and The Giver. Some remarks on ideal societies (...) - 34 3. Notes about the possible and impossible of utopia - 39 -/- III. The limits of Zombies films are the limits of philosophy? 1. Are zombies real? From folklore to films - 46 2. The mind-body problem and the empty-minded zombies? - 54 3. The fallacy of the question. Zombies films and philosophy with no limit - 61 -/- IV. Lucy - why the brain cannot be a screen 1. Lucy and some other movies - The ten percent of the brain myth - 67 2. The enhancement of humanity -The pos-humanism after Nietzsche – 71 3. About the mind and the brain. Lucy or why the brain cannot be a screen – 74 -/- V. Viktor Navorski and Sir Alfred: the limits of consciousness at the border of chaos 1. About the terminal, Locke and Lipovetsky - 83 2. Being someone at a non-place - 87 3. Reality vs fiction. Merhan Karimi Nasseri as Sir Alfred - 89 -/- VI. Alienation and slavery from Precious or what we do not want to see 1. Cinema as a moment or the exclusive experience of feeling cinema - 97 2. Two movies, only one reality - 101 3. To conclude: the paradox of precious silence or what we don't want to see - 104 -/- VII. Philosophy of time and being in Alice through the looking glass 1. Some initial considerations on Alice - 113 2. The impossible and the possible in Alice’s time - 116 3. About time and subjectivity and subjectivity in time – 120 -/- References - cxxv. (shrink)