We recall, "a priori," numeric energy expression: -/- Energy Numbers -/- $\begin{gathered}\mathcal{V}=\left\{f \mid \exists\left\{e_1, e_2, \ldots, e_n\right\} \in E \cup R\right\} \\ \mathcal{V}=\left\{f \mid \exists\left\{e_1, e_2, \ldots, e_n\right\} \in E, \text { and }: E \mapsto r \in R\right\} \\ \mathcal{V}=\left\{E \mid \exists\left\{a_1, \ldots, a_n\right\} \in E, E \not \neg r \in R\right\}\end{gathered}$ -/- We now introduce the set of optimized energy numbers: -/- ($H_a \in \mathcal{H}$ or $P^n = NP$ or $(P,\mathcal{L},F) = NP$). -/- Based on our formulation of (...) the bi-objective optimization task, we can make the following mathematical inferences: -/- 1. If the optimized energy numbers set $\mathcal{N}_H$ is equal to the original energy numbers set $\mathcal{E}$, i.e. $\mathcal{N}_H = \mathcal{E}$, then the maximum optimization score is achieved, i.e. the bi-objective optimization task is solved. This implies that there exists at least one solution to the optimization problem and $H_a \in \mathcal{H}$, where $H_a$ is the hypothesis that states the existence of an efficient algorithm to solve the problem. -/- 2. If the optimized energy numbers set $\mathcal{N}_H$ is a subset of the original energy numbers set $\mathcal{E}$, i.e. $\mathcal{N}_H \subset \mathcal{E}$, then the optimization score is less than the maximum score. This indicates that there may exist more efficient algorithms to solve the problem, and the hypothesis $H_a$ is still possible. -/- 3. If the optimized energy numbers set $\mathcal{N}_H$ is a superset of the original energy numbers set $\mathcal{E}$, i.e. $\mathcal{N}_H \supset \mathcal{E}$, then the optimization score is higher than the maximum score. This implies that the optimization problem may be easier than initially thought, and $P^n = NP$, or at least some form of $NP$-completeness. -/- 4. If the optimized energy numbers set $\mathcal{N}_H$ is a strict subset of the original energy numbers set $\mathcal{E}$, i.e. $\mathcal{N}_H \subsetneq \mathcal{E}$, and $P^n \neq NP$, then it can be concluded that the optimization problem is complex but there may exist algorithms that can efficiently approximate the solution. -/- 5. If the optimized energy numbers set $\mathcal{N}_H$ is empty, i.e. $\mathcal{N}_H = \emptyset$, then it can be inferred that the optimization problem is infeasible, i.e. no efficient algorithm exists to solve it, and $H_a$ is false. -/- 6. Comparing the two objectives in the bi-objective optimization task, we can make the following statements: -/- - The first objective, $\frac{\delta_{v(f)}(\mathbf{v}, \mathbf{w_{max}})} {\langle \mathbf{v_f}, \mathbf{1_f}\rangle}$, measures the efficiency of the algorithm and its ability to find low energy numbers. - The second objective, $\rho(\mathcal{N}_H)$, measures the accuracy of the algorithm in terms of loss and perplexity on the HyperLanguageModel. - Therefore, by optimizing both objectives simultaneously, we aim to find an efficient algorithm that also minimizes the loss and perplexities on the HyperLanguageModel. - If the optimization task is successfully solved, then the algorithm achieves both high efficiency and high accuracy. This would imply that the algorithm is able to find low energy numbers effectively and also generalize well on the HyperLanguageModel. -/- The optimized energy numbers aim to find a set of numbers $\mathbf{v}$ that maximize the bi-objective optimization task, while also minimizing the loss and perplexity of the HyperLanguageModel. This is achieved by finding the set of numbers that have the highest delta value and the lowest perplexity, resulting in a more optimized and efficient set of energy numbers. -/- By comparing the optimized energy numbers to the original set, we can see that the optimized set may have a higher delta value and a lower perplexity, indicating that it is a better set of numbers for the given task. This shows that the optimized energy numbers have successfully achieved their goal of maximizing efficiency while minimizing loss and perplexity. (shrink)

Higher - dimensional calculus and integral transformation play crucial roles in advancing our understanding of complex systems in mathematics and theoretical physics . Integral transformations are instrumental in simplifying complex differential equations, enabling the resolution of multi - dimensional problems that arise in various scientific fields . This paper aims to delve into a specific higher - dimensional integral transformation defined by the axioms \(F[q, s, l, \alpha]\) and \(G[q, s, l, \beta, c]\) . We start by outlining the axioms (...) which define the functions \(F\) and \(G\) . Specifically, Axiom 1 defines \(F\) as a function of four variables : \(q\), \(s\), \(l\), and \( \alpha\), whereas Axiom 2 defines \(G\) as a function that additionally includes variables \( \beta\) and \(c\) . Axiom 3 relates \(h\) and \(l\) via a sine function . The core of our investigation is the integral transformation expressed as a five - dimensional integral involving \(G\) and proving its equivalence to \(F\), provided a specific condition on \(c\) holds . We approach this problem by first deriving the expression for \(c\) through detailed differentiation of \(F\) and equating it to \(G\) . The derivation involves advanced calculus techniques and symbolic mathematics to solve the resulting equations . We then verify the derived expression for \(c\) by substituting it back into the relationship between \(F\) and \(G\), ensuring that the equality holds under integral transformation . Finally, to corroborate our findings, we employ visualizations through multidimensional contour plots to illustrate the relationship between the derived expressions . This provides an intuitive confirmation of the mathematical consistency and validity of the transformation . This paper contributes to the field by providing a nuanced and detailed examination of higher - dimensional integral transformations and their underlying mathematical structures . The results have potential implications for theoretical physics, particularly in areas involving complex systems and multi - dimensional analyses . (shrink)

DESENVOLVIMENTO EMBRIONÁRIO E DIFERENCIAÇÃO SEXUAL -/- E. I. C. da Silva Departamento de Agropecuária – IFPE Campus Belo Jardim Departamento de Zootecnia – UFRPE sede -/- 1.1 INTRODUÇÃO O sexo foi definido como a soma das diferenças morfológicas, fisiológicas e psicológicas que distinguem o macho da fêmea permitindo a reprodução sexual e assegurando a continuidade das espécies. Os processos de diferenciação sexual são realizados durante o desenvolvimento embrionário, onde ocorre a proliferação, diferenciação e maturação das células germinativas e primordiais, precursoras (...) de ovócitos e espermatozoides em fêmeas e machos, respectivamente. Assim, os embriões machos e fêmeas iniciam o seu desenvolvimento de forma semelhante, de modo que em ambos os sexos se estabelecem em estruturas idênticas a partir das quais se formarão os órgãos reprodutores correspondentes a cada sexo. O conhecimento da origem e do desenvolvimento do aparelho genital é indispensável para entender sua função e as alterações que produzem infertilidade ou esterilidade. 1.2 DETERMINAÇÃO DO SEXO CROMOSSÔMICO Nos mamíferos, o sexo cromossômico é determinado no momento da fertilização, quando um óvulo, que contém um cromossomo X, é fecundado por um espermatozoide portador de um cromossomo X ou um cromossomo Y. No primeiro caso, o complemento cromossômico seria XX, o que originaria uma fêmea (sexo homogamético), e no segundo daria como resultado um macho com a fórmula cromossômica XY (sexo heterogâmico). 1.3 A GÔNADA INDIFERENCIADA A primeira manifestação das gônadas se aprecia no embrião em forma de um par de eminências longitudinais chamadas cristas ou dobras gonodais, situadas em ambos os lados da linha média entre os mesonefros (rins em desenvolvimento) e do mesentério dorsal. Nos embriões dos mamíferos, as células germinativas primordiais (CGP) manifestam-se em estágios precoces do desenvolvimento, podendo ser detectadas pela primeira vez na metade da gastrulação. As CGP são células grandes, de citoplasma claro e núcleo grande e redondo, localizadas na parede do saco vitelino, perto do alantoide. Essas células possuem grande capacidade de proliferação e vão migrar desde o endoderma do intestino e o epitélio do saco vitelino, através do mesentério, até as cristas gonodais. Isso ocorre por volta do 26° dia da gestação no bovino. Sua migração realiza-se graças aos movimentos de translocação passiva e deslocamento ameboide ativo. Desconhece-se o mecanismo pelo qual estas células são dirigidas para as cristas gonodais, porém foram estudadas algumas moléculas que se expressam durante sua migração e que poderiam desempenhar um papel importante na diferenciação deste tipo celular. A fosfatase alcalina é uma enzima que tem sido usada como marcador de CGP para determinar a sua origem e migração. Num estudo recente, foi inserido um marcador fluorescente que se exprime unicamente nas células germinativas primordiais de embriões transgênicos, e utilizando este marcador e a fosfatase alcalina determinou-se a origem e o padrão de migração destas células. O primeiro sinal de diferenciação das células germinativas primordiais é a expressão de fosfatase alcalina, e esta apareceu pela primeira vez na parte mais posterior da linha primitiva. No sétimo dia de desenvolvimento no embrião do camundongo, o endoderma visceral (AF+) é substituído pelo endoderma definitivo (AF-) originado na parte anterior da linha primitiva. O fator de transcrição Oct-4 é expresso nas CGP de ambos os sexos, pelo que acredita-se estar envolvido na mantença a totipotêncialidade das células. O receptor tirosina quinase, cujo ligante é o fator de Steel, é outra das moléculas que expressam as CGP. Tem sido demonstrado que este receptor possui um papel muito importante na sobrevivência deste tipo celular. Existem outros fatores que promovem a sobrevivência e/ou proliferação de CGP in vitro. Em experiências realizadas com o fator de transformação beta I (TGFβ-I), observou-se que este tem um efeito negativo sobre a proliferação das CGP. Outra atividade que tem sido postulada a este fator é o de um agente quimioatraente que possivelmente possa direcionar a migração destas células para a gônada. a) Um formado pelas células germinativas primordiais (precursoras dos gametas masculinos ou femininos), rodeadas de células somáticas das quais posteriormente se derivarão as células de Sertoli no macho e as células da granulosa na fêmea. b) O tecido que formará o estroma da gônada: tecido conjuntivo, vasos sanguíneos e as células intersticiais com atividade esteroidogênica (células de Leydig no testículo e a teca interna do ovário). As células somáticas do primórdio gonodal originam-se do mesoderma. Inicialmente são de três tipos: mesenquimáticas, mesoteliais e endoteliais. As células mesenquimáticas e mesoteliais iniciam grande atividade proliferativa ao chegar as CGP. Observa-se então uma condensação de células de origem mesotelial e mesenquimatoso que forma um agregado compacto denominado "blastema gonodal". A partir deste primórdio embrionário, diferenciam-se dois tecidos gonodais: os cordões sexuais e o estroma. Os cordões sexuais são arranjos epiteliais que se encontram delimitados por uma folha basal, e dentro deles encontramos as CGP. Por sua vez, no estroma encontram-se células do tipo mesenquimático e vasos sanguíneos. Neste momento, as gônadas são indiferenciadas e bipotencialmente sexuais, sendo impossível diferenciar, morfologicamente, uma gônada masculina de uma feminina, mas no caso dos machos genéticos já existe uma diferenciação da gônada a nível molecular. Nesta fase já se encontram presentes as estruturas das quais se desenvolvem os dutos mesonéfricos ou de Wolff precursores do aparelho genital masculino e os dutos paramesonéfricos ou de Müller que darão origem ao aparelho reprodutor feminino. Há uma série de fatores envolvidos no desenvolvimento precoce da gônada, entre os quais o fator esteroidogênico I (SFI: Steroidogenic fator l), que é um membro da subfamília de receptores nucleares, receptores órfãos. Este fator de transcrição tem um local de ligação ao DNA composto por dois dedos-de-Zinc. O SFI foi identificado como um ativador de genes envolvidos na biossíntese de esteroides em diferentes células. O SFI está presente durante o desenvolvimento embrionário em regiões associadas com funções endócrinas como gônadas, adrenais, pituitárias e hipotálamos. Os animais homozigotos para o gene SFI defeituoso, necessitam de gônadas e adrenais e têm a função gonadotrófica alterada. Os ratos sem SFI carecem de gonadotrofos e têm um desenvolvimento anormal do núcleo ventro-medial do hipotálamo; em particular as gônadas deixam de se desenvolver entre os dias 11 a 15 e degeneram-se por apoptose. No entanto, a crista genital forma-se e é colonizada pelas células germinativas, o que indica que estas continuam a receber o sinal adequado para a sua migração. Portanto, o SFI não está envolvido no desenvolvimento precoce da gônada e do sistema urogenital, mas parece estar envolvido na manutenção do crescimento das células somáticas presentes na gônada indiferenciada. O gene associado ao tumor de Wilms (WTI: Wilm's tumor Associated) está envolvido no desenvolvimento da gônada e do rim. Durante o desenvolvimento embrionário, WTI se expressa em todo o mesoderma intermediário e posteriormente na gônada indiferenciada, bem como no rim em formação. WTI regula o sinal indutivo do mesênquima para o epitélio celômico dos mesonefros. Se este for o caso, então WTI é responsável pelo crescimento da crista genital ao dirigir a entrada do epitélio celômico. Dado que estas células darão origem às células de Sertoli, a carência de WTI pode causar o desenvolvimento de embriões XY como fêmeas simplesmente porque não se formam as células de Sertoli. Em geral, todos os genes importantes na diferenciação do mesoderma intermediário e do sistema urogenital intervêm no desenvolvimento da gônada precoce. 1.4 DIFERENCIAÇÃO GONODAL O desenvolvimento das gônadas e ductos genitais descritos até o momento, é o mesmo para ambos os sexos. Igualmente, os genes descritos, que estão envolvidos no desenvolvimento das gônadas, ductos genitais e migração das células germinativas, afetam igualmente os embriões com genótipo XX ou XY. A gônada primitiva consiste anatomicamente de uma medula (interna) e uma crosta (externa), e de acordo com o local onde ocorre a colonização das células germinativas, diferenciara em testículo ou um ovário, respectivamente. Nos mamíferos, a primeira manifestação estrutural de diferenciação sexual é detectada na gônada dos machos, onde as células germinativas estão localizadas na medula. A diferenciação do testículo inicia-se quando os cordões sexuais se separam do epitélio celômico como consequência dos arranjos produzidos por uma invasão do mesênquima e vasos sanguíneos que provoca a compactação dos cordões, agora denominados cordões testiculares. As células que rodeiam os cordões se achatam e formam as células mioides, que são responsáveis pela formação das membranas basais. As células do epitélio interno, ou seja, as células de Sertoli, têm duas funções principais: o suporte das CGP e a síntese da hormona antimulleriana, responsável pela regressão dos ductos de Müller e secretada durante o período de diferenciação sexual. As células do estroma que rodeiam os cordões testiculares diferenciam-se para formar vários tipos de células: células mioides, fibroblastos, endotélio e células de Leydig, que são as mais importantes pela sua atividade endócrina. Posteriormente, os cordões testiculares dão origem aos túbulos seminíferos, que contêm o epitélio que produzirá os espermatozoides ao chegar à puberdade. Na fêmea, durante os estágios iniciais de diferenciação gonodal, não se observam mudanças em relação à gônada indiferenciada, só pode-se observar um certo crescimento devido à proliferação de células somáticas e germinativas. As células germinativas iniciam um período de proliferação, que termina com o início da meiose. Iniciada a meiose, dá-se o processo de foliculogênese; neste momento os cordões epiteliais se fragmentam, de tal maneira que cada ovócito fica rodeado de células epiteliais cobertas por uma folha basal fina (figura 1). Para que a gônada primitiva se desenvolva em testículo é indispensável a presença do cromossoma Y, independentemente do número de cromossomas X que contenha o genoma de um indivíduo. O gene determinante do testículo encontra-se localizado no cromossoma Y, denominado sry em ratos e SRY em humanos. O gene sry se expressa durante o desenvolvimento embrionário na crista genital de embriões de camundongos. A expressão é detectável no dia 10,5, pouco depois do aparecimento das cristas genitais, atinge o seu máximo durante o dia 11,5 e mantém-se até pouco depois de ocorrerem os primeiros sinais morfológicos de diferenciação testicular no dia 12,5. Este padrão de expressão é compatível com a teoria de que sry atua induzindo a ativação dos genes (figura 2) que conduzem ao desenvolvimento testicular, sem que exista a necessidade da expressão contínua de sry para manter a diferenciação do testículo após o dia 12,5. Como mencionado anteriormente, a gônada primitiva é composta por vários tipos de células. No entanto, as células germinativas primordiais não são o local de expressão do sry, já que os embriões que necessitam de células germinativas mantêm a expressão de sry e desenvolvem o sexo gonodal normalmente. As células somáticas na gônada em desenvolvimento incluem também as células de suporte. Sabe-se que é nestas células que o sry é expresso para que se diferenciem em células de Sertoli, e a expressão transitória de sry indica que deve ativar a outros genes para a manutenção das células de Sertoli. Uma vez diferenciadas as células de Sertoli, elas se encarregarão da diferenciação do resto das células na gônada. -/- Figura 1: Representação da diferenciação dos órgãos genitais internos. Adaptado de BRONSON, 1989. Figura 2: Cascada de genes envolvidos na diferenciação sexual, adaptado de KOOPMAN, 1999. O fator sry é necessário para a diferenciação do testículo. Embora não se conheçam os genes que provavelmente regulam esse gene, estudos realizados em camundongos demonstram que este gene parece coordenar-se com certos genes autossômicos. Entre estes genes autossômicos, o sox9, que é produzido pelas células de Sertoli uma vez que são estimuladas por sry, de modo que sox9 é um dos genes relacionados estruturalmente com sry. O Sox9 funciona como um fator de transcrição, mas não se sabe se a proteína tem qualquer outra função estrutural; este gene exprime-se abundantemente nos condrócitos e está relacionado com defeitos do aparelho ósseo chamados displasia campomélica. Curiosamente, os pacientes XY com esta condição sofrem frequentemente de reversão do sexo. O Sox9 é um dos poucos genes, além do SRY, do qual as mutações demonstraram interferir com a determinação sexual masculina. No entanto, apenas 75% dos pacientes com anomalias esqueléticas de tipo displasia campomélica têm reversão sexual e não foram encontrados casos de reversão sexual devido a um defeito de Sox9 que não seja acompanhado de defeitos esqueléticos. Isso indica que o Sox9 é apenas um membro da rede de genes que são ativados para determinar a diferenciação sexual, enquanto a rota que rege a condrogênese é mais sensível a perturbações deste. O momento em que se detecta a expressão do gene Sox9 (11dpc em ratos) coincide com a máxima expressão de sry, o que poderia indicar a possibilidade de que sry regule positivamente a Sox9. De fato, na região do promotor de Sox9 há um local de união ao que potencialmente se pode unir o sry. A expressão de Sox9 durante a diferenciação sexual sugere um papel abaixo de sry na diferenciação das células de Sertoli. O cromossoma X também é importante na diferenciação gonodal. O gene DAX-I foi isolado do lócus DSS (Dosage sensitive sex reversal) do cromossoma X. DAX-I é parte da cascata de determinação sexual, mas não é necessário para a formação do testículo. DAX-I é um membro dos receptores nucleares conhecidos como receptores órfãos. Este gene demonstrou ser um poderoso repressor da transcrição de SFI e de vários genes. Os padrões de expressão de DAX-I são complementares daqueles de SFI, ambos expressos nas cristas genitais. Em resumo, dada a evidência exposta, desenvolveu-se a hipótese de que DAX-I é um antagonista de sry; esse antagonismo é dependente dos níveis relativos de DAX-I e sry e de um limiar que varia de espécie para espécie. A DAX-I foi classificada como o gene antitestículo. Na fêmea (cariótipo XX) é importante que ocorra a inativação de um dos cromossomas sexuais X para que se mantenha o equilíbrio genético ao igualar o conteúdo de DNA dos cromossomas. Esse cromossoma inativado constitui o chamado corpúsculo de Barr. No entanto, para que a meiose se realize, é necessário dos dois cromossomas X ativos nos ovócitos para assegurar a diferenciação ovárica e a fertilidade. 1.5 DIFERENCIAÇÃO DOS DUCTOS SEXUAIS O embrião possui, além das gônadas indiferenciadas, dois sistemas de ductos: os de potencialidade masculina denominam-se ductos de Wolff ou mesonéfricos, e os de potencialidade feminina se chamam ductos de Müller ou paramesonéfricos (figura 1). Se a diferenciação gonodal levou à formação de um testículo, a partir do ducto mesonéfrico ou de Wolff se desenvolverão os ductos eferentes, o epidídimo, os ductos deferentes e as vesículas seminais. As hormonas importantes no desenvolvimento do aparelho genital masculino são a testosterona, produzida pelas células de Leydig, e sua forma 5α reduzida, a 5α di-hidrotestosterona. Acredita-se que a testosterona é responsável pela virilização dos ductos de Wolff, e a di-hidrotestosterona dos órgãos genitais externos. No macho, os canais de Müller atrofiam-se devido à ação de uma hormona fetal de origem testicular denominada hormona inibidora das estruturas de Müller (HIM) ou hormona antimulleriana. Este processo começa assim que os cordões espermáticos se formam e se diferenciam as células de Sertoli. A existência de HIM foi proposta baseada em estudos realizados em bezerras freemartin, devido à existência de uma hormona responsável pela atresia dos ductos de Müller que na fêmea dá origem ao útero e aos ovidutos. Essa hormona provoca a involução do aparelho genital do bovino nas gestações gemelares nas quais os produtos de diferente sexo têm comunicação sanguínea por ter ocorrido a anastomose dos vasos de ambas as placentas (figura 3). A HIM é uma glicoproteína pertencente à subfamília de TGFβ, é expressa pelas células que darão origem às células de Sertoli e é um dos primeiros marcadores de diferenciação nestas células. A HIM é secretada na vida adulta pelas células de Sertoli no testículo e por células da granulosa no ovário. No rato a HIM é expressa-se no 12° dia em um teste padrão que segue muito de perto o aumento na expressão de sry. No macho, esta secreção de HIM continua durante a vida fetal e adulta, contudo os níveis de HIM declinam na puberdade devido a um aumento na secreção de testosterona. Vários fatores intervêm na regulação do gene de HIM, incluindo os acima descritos SFI e Sox9. O gene HIM contém segmentos de DNA que são conservados em várias espécies de vertebrados. Existe um nexo de ligação para SFI, que ativa a transcrição de HIM. A mutação no local de ligação de SFI resulta em reversão do sexo em indivíduos XY incluindo genitais femininos normais, presença de um útero formado enfatizando a importância de SFI na determinação sexual e na expressão de HIM. Embora SFI seja um bom candidato como regulador de HIM, é expresso em outras células, como as de Leydig e adrenais, que não expressam HIM. Em contrapartida, Sox9 é expresso unicamente nas células de Sertoli que são as produtoras de HIM. O gene HIM também tem um nexo de ligação para Sox9. Além disso, Sox9 pode atuar sinergicamente com SFI para promover a secreção de HIM. Ao contrário destes dois fatores de transcrição, DAX-I antagoniza a ação de Sox9 e provavelmente SFI sobre o promotor de HIM. Assim, para que as células de Sertoli secretem HIM, a transcrição de DAX-I deve diminuir. Figura 3: Representação da diferenciação dos órgãos genitais externos. Adaptado de BRONSON, 1989. Os ductos de Wolff tornam-se o sistema de ejaculação do macho. A porção mais próxima dos testículos dá origem ao epidídimo, a parte central ao ducto deferente e a porção mais distal às vesículas seminais. A próstata e a parte membranosa da uretra do macho desenvolvem-se a partir da porção pélvica do seio urogenital. A virilização e diferenciação dos ductos de Wolff dependem da produção de testosterona pelo testículo. Quanto aos órgãos genitais externos do macho, o tubérculo genital é ampliado e as dobras uretrais se fundem para formar a uretra peniana. A fusão das dobras uretrais aproxima os tubérculos genitais para formar o escroto (figura 4). Figura 4: Diferenciação do aparelho genital da fêmea e do macho. Adaptado de KOOPMAN, 1989. A diferenciação dos órgãos genitais da fêmea ocorre de forma passiva, já que a ausência de testículos e por isso da hormona inibidora dos ductos de Müller (HIM), assim como dos andrógenos virilizantes, favorece o desenvolvimento dos ductos de Müller, enquanto os de Wolff sofrem atrofia. A porção cefálica dos ductos de Müller dá origem aos ovidutos, que na sua terminação caudal se fundem com o útero. O contato dos ductos de Müller com o seio urogenital induz uma intensa proliferação celular que resulta na formação da área uterovaginal localizado entre o seio urogenital e os ductos de Müller. As células do prato uterovaginal proliferam e aumentam a distância entre as duas estruturas criando o espaço que formará a vagina quando o prato é canalizado e forma um lúmen. Em contraste com o que ocorre no macho, na fêmea a maior parte do seio urogenital se mantém exposta na superfície da abertura onde desembocam a vagina e a uretra. O tubérculo urogenital da fêmea tem um crescimento limitado e forma o clitóris. A sequência de passos da diferenciação sexual do aparelho genital é resumida na tabela 1. Tabela 1: Destino em desenvolvimento dos rudimentos sexuais dos fetos macho e fêmea dos mamíferos -/- Rudimento sexual Macho Fêmea Gônada Testículo Ovário Ductos de Müller (Paramesonéfricos) Vestígios Útero, parte da vagina, ovidutos Ductos de Wolff (Mesonéfricos) Ductos eferentes deferentes, epidídimo, vesículas seminais Vestígios Seio urogenital Uretra, próstata, glândulas bulbouretrais Parte da vagina, uretra, vestíbulo, glândulas vestibulares Tubérculo genital Pênis Clitóris Pregas vestibulares Escroto Lábios vulvares Fonte: HAFEZ, 2004. 1.6 DIFERENCIAÇÃO SEXUAL DO HIPOTÁLAMO Os processos de diferenciação sexual não se limitam apenas às células somáticas do organismo do feto, mas incluem também os centros nervosos superiores do cérebro. Assim, da mesma maneira que a gônada e os ductos sexuais se desenvolvem para o tipo feminino ou masculino, propôs-se que o cérebro pode ser "masculinizado" ou permanecer "Feminizado". A diferenciação do hipotálamo vai depender do ambiente esteroidal do neonato e ocorre na fase perinatal. Estes eventos serão de grande transcendência na vida reprodutiva do indivíduo. Tanto a fêmea como o macho nascem com a capacidade de secreção de gonadotropinas de acordo com um padrão cíclico; contudo, no macho, a exposição do hipotálamo à ação dos andrógenos testiculares durante os primeiros dias da vida extrauterina provoca a masculinização, com o qual o hipotálamo do macho é programado para que a secreção de gonadotropinas se realize a um ritmo relativamente constante por parte da hipófise (secreção tônica). Na fêmea, tanto a secreção tônica como a cíclica se conservam. No entanto, observou-se que a injeção de testosterona ou o transplante de testículo na rata fêmea durante os primeiros dias de vida, suprime a sua futura atividade estral (secreção cíclica). Por outro lado, se os ovários forem transplantados para o rato macho normal castrado na idade adulta, o animal não desenvolve qualquer atividade cíclica, mas se os machos transplantados forem castrados ao nascer, o ovário é capaz de efetuar mudanças cíclicas e ovulações. Isto foi demonstrado em roedores, mas não em animais domésticos ou na espécie humana. Portanto, o padrão de secreção de gonadotropinas, seja cíclico ou tônico, não depende da hipófise, mas do hipotálamo e sua correta diferenciação. 1.7 CONCLUSÕES A maioria dos conhecimentos no campo da biologia do desenvolvimento e, muito especificamente, dos processos de diferenciação sexual têm sido originados de estudos relacionados com desordens congênitas, que na sua maioria devem-se a defeitos de genes específicos. A análise detalhada destas desordens permitiu entender alguns mecanismos endócrinos, moleculares e genéticos envolvidos na diferenciação sexual. A identificação do gene sry como determinante do testículo foi uma contribuição crucial e abriu as portas à compreensão dos mecanismos moleculares e celulares relacionados com o desenvolvimento do testículo. Se este gene não estiver presente, é criado um programa genético alternativo para levar a cabo a diferenciação gonodal para o ovário. Finalmente, devemos ter presente que é necessária uma correlação entre mudanças morfológicas e expressão de genes durante o desenvolvimento para entender os mecanismos relacionados com a diferenciação. -/- Apoio -/- Realização -/- REFERÊNCIAS BIBLIOGRÁFICAS ANDERSON, Robert et al. The onset of germ cell migration in the mouse embryo. Mechanisms of development, v. 91, n. 1-2, p. 61-68, 2000. AUSTIN, Colin Russell; SHORT, R. V. Reproduction in Mammals: Volume 1, Germ Cells and Fertilization. Londres: Cambridge University Press, 1972. BRONSON, Franklin H. Mammalian reproductive biology. Chicago: University of Chicago Press, 1989. BUEHR, Mia. The primordial germ cells of mammals: some current perspectives. Experimental cell research, v. 232, n. 2, p. 194-207, 1997. BYSKOV, Anne G. Differentiation of mammalian embryonic gonad. Physiological reviews, v. 66, n. 1, p. 71-117, 1986. CAPEL, Blanche et al. Migration of mesonephric cells into the mammalian gonad depends on Sry. Mechanisms of development, v. 84, n. 1-2, p. 127-131, 1999. CAPEL, Blanche. The battle of the sexes. Mechanisms of development, v. 92, n. 1, p. 89-103, 2000. DERIVAUX, Jules; BARNABÉ, Renato Campanarut. Reprodução dos animais domésticos. Zaragoza: Acribia, 1980. DOMENICE, Sorahia et al. Aspectos moleculares da determinação e diferenciação sexual. Arquivos Brasileiros de Endocrinologia & Metabologia, v. 46, n. 4, p. 433-443, 2002. DONAHOE, Patricia K. et al. Mullerian inhibiting substance activity in bovine fetal, newborn and prepubertal testes. Biology of reproduction, v. 16, n. 2, p. 238-243, 1977. HAFEZ, Elsayed Saad Eldin; HAFEZ, B. Reprodução animal. São Paulo: Manole, 2004. HANLEY, Neil A. et al. Steroidogenic factor 1 (SF-1) is essential for ovarian development and function. Molecular and cellular endocrinology, v. 163, n. 1-2, p. 27-32, 2000. HIORT, Olaf; PAUL-MARTIN, H. The molecular basis of male sexual differentiation. European journal of endocrinology, v. 142, n. 2, p. 101-110, 2000. HOLY, Lubos; MARTÍNEZ JÚSTIZ, G. Colab. Biología de la reproducción bovina. Havana: Revolucionária, 1975. JOSSO, Nathalie et al. The role of anti-Müllerian hormone in gonadal development. Molecular and cellular endocrinology, v. 145, n. 1-2, p. 3-7, 1998. JOST, Alfred et al. Studies on sex differentiation in mammals. In: Proceedings of the 1972 Laurentian Hormone Conference. Londres: Academic Press, 1973. p. 1-41. KNOBIL, Ernst. Knobil and Neill's physiology of reproduction. EUA: Gulf Professional Publishing, 2006. KOFMAN ALFARO, S.; MERCHANT LARIOS, H.; PEREZ PALACIOS, G. Diferenciacion sexual. I. Bases biologicas del dimorfismo sexual. Rev. invest. clín, p. 349-59, 1982. KOOPMAN, Peter. Sry and Sox9: mammalian testis-determining genes. Cellular and Molecular Life Sciences CMLS, v. 55, n. 6-7, p. 839-856, 1999. MCDONALD, L. E. Veterinary endocrinology. Lea & Febiger, Philadelphia, Pa, 1969. MEIZEL, S.; JOHNSON, M. H. Development in mammals. MH Johnson, Ed, v. 3, p. 1-64, 1978. MELLO, Maricilda Palandi de; ASSUMPÇÃO, Juliana de G.; HACKEL, Christine. Genes envolvidos na determinação e diferenciação do sexo. Arquivos Brasileiros de Endocrinologia & Metabologia, v. 49, n. 1, p. 14-25, 2005. -/- REFERÊNCIAS BIBLIOGRÁFICAS MERCHANT-LARIOS, H. Ovarian differentiation. The Vertebrate Ovary, p. 47-81, 1978. MIES FILHO, Antonio. Reprodução dos animais. Porto Alegre: Sulina, 1987. NEF, Serge; PARADA, Luis F. Hormones in male sexual development. Genes & Development, v. 14, n. 24, p. 3075-3086, 2000. PARKER, Keith L.; SCHEDL, Andreas; SCHIMMER, Bernard P. Gene interactions in gonadal development. Annual review of physiology, v. 61, n. 1, p. 417-433, 1999. SWAIN, Amanda; LOVELL-BADGE, Robin. Mammalian sex determination: a molecular drama. Genes & development, v. 13, n. 7, p. 755-767, 1999. WILHELM, Dagmar; PALMER, Stephen; KOOPMAN, Peter. Sex determination and gonadal development in mammals. Physiological reviews, v. 87, n. 1, p. 1-28, 2007. WILSON, Jean D.; GRIFFIN, James E.; GEORGE, Fredrick W. Sexual differentiation: early hormone synthesis and action. Biology of reproduction, v. 22, n. 1, p. 9-17, 1980. -/- Emanuel Isaque Cordeiro da Silva Belo Jardim, 07 de Maio de 2020. (shrink)

Epistemic burdens – the nature and extent of our ignorance (that and how) with respect to various courses of action – serve to determine our incentive structures. Courses of action that seem to bear impossibly heavy epistemic burdens are typically not counted as options in an actor’s menu, while courses of action that seem to bear comparatively heavy epistemic burdens are systematically discounted in an actor’s menu relative to options that appear less epistemically burdensome. That ignorance serves to determine what (...) counts as an option means that epistemic considerations are logically prior to moral, prudential, and economic considerations: in order to have moral, prudential, or economic obligations, one must have options, and epistemic burdens serve to determine our options. One cannot have obligations without doing some epistemic work. We defend this claim on introspective grounds. We also consider how epistemic burdens distort surrogate decision-making. The unique epistemology of surrogate cases makes the priority of the epistemic readily apparent. We then argue that anyone who accepts a principle similar to ought implies can is committed to the logical priority of the epistemic. We also consider and reject several possible counterarguments. -/- . (shrink)

In this paper I’ll examine whether we could be justified in attributing consciousness to artificial intelligent systems. First, I’ll give a brief history of the concept of artificial intelligence (AI) and get clear on the terms I’ll be using. Second, I’ll briefly review the kinds of AI programs on offer today, identifying which research program I think provides the best candidate for machine consciousness. Lastly, I’ll consider the three most plausible ways of knowing whether a machine is conscious: (1) an (...) AI demonstrates a sufficient level of organizational similarity to that of a human thinker, (2) an inference to the best explanation, and (3) what I call “punting to panpsychism”, i.e., the idea that if everything is conscious, then we get machine consciousness in AI for free. However, I argue that all three of these methods for attributing machine consciousness are inadequate since they each face serious philosophical problems which I will survey and specifically tailor to each method. (shrink)

The practice of medicine frequently involves the unconsented restriction of liberty. The reasons for unilateral liberty restrictions are typically that being confined, strapped down, or sedated are necessary to prevent the person from harming themselves or others. In this paper, we target the ethics of chemical restraints, which are medications that are used to intentionally restrict the mental states associated with the unwanted behaviors, and are typically not specifically indicated for the condition for which the patient is being treated. Specifically, (...) we aim to identify the conditions under which chemical restraints are ethically permissible. It is wrong to assume that what is morally true of physical restraints is also true of chemical restraints. Our aim is thus to identify the conditions under which chemical restraints are permissible while distinguishing these conditions from those of the application of physical restraints. (shrink)

It has recently been argued that a person’s moral judgments (about both their own and others’ actions) are constrained by the nature and extent of their relevant ignorance and, thus, that such judgments are determined in the first instance by the person’s epistemic circumstances. It has been argued, in other words, that the epistemic is logically prior to other normative (e.g., ethical, prudential, pecuniary) considerations in human decision-making, that these other normative considerations figure in decision-making only after (logically and temporally) (...) relevant ignorance has constrained the decision-maker’s menu of options. If this is right, then a person’s moral judgments in some set of circumstances should vary with their knowledge and ignorance of these circumstances. In this study, we test the hypothesis of the logical priority of the epistemic. We describe two experiments in which subjects’ knowledge and ignorance of relevant consequences were manipulated. In the second experiment, we also compared the effect of ignorance on moral judgments with that of personal force, a factor previously shown to influence moral judgments. We found broad empirical support for the armchair arguments that epistemic considerations are logically prior to normative considerations. (shrink)

Some theorists argue that moral bioenhancement ought to be compulsory. I take this argument one step further, arguing that if moral bioenhancement ought to be compulsory, then its administration ought to be covert rather than overt. This is to say that it is morally preferable for compulsory moral bioenhancement to be administered without the recipients knowing that they are receiving the enhancement. My argument for this is that if moral bioenhancement ought to be compulsory, then its administration is a matter (...) of public health, and for this reason should be governed by public health ethics. I argue that the covert administration of a compulsory moral bioenhancement program better conforms to public health ethics than does an overt compulsory program. In particular, a covert compulsory program promotes values such as liberty, utility, equality, and autonomy better than an overt program does. Thus, a covert compulsory moral bioenhancement program is morally preferable to an overt moral bioenhancement program. (shrink)

It is plausible that current generations owe something to future generations. One possibility is that we have a duty to not harm them. Another possibility is that we have a duty to protect them. In either case, however, to satisfy the duties to future generations from environmental or political degradation, we need to engage in widespread collective action. But, as we are, we have a limited ability to do so, in part because we lack the self-discipline necessary for successful collective (...) action. Given that having an obligation hinges on being able to satisfy it, the apparent duty to future generations is at odds with our apparent inability to satisfy it. Thus, we either need to rethink our duties to future generations or rethink the nature of our abilities. I argue in this chapter that we should rethink the nature of our abilities. Specifically, we should enhance our self-discipline, which is distinct from enhancements of motivation, judgment, or emotion. Even the most intelligent, motivated, and empathetic actor is likely to slip up, which encourages others to withdraw their cooperation. Without the necessary self-discipline to sustain our public cooperative behavior, collective action is likely to fail, leaving us with one alternative: to abandon our duties to future generations. (shrink)

Recent work has defended “Euclidean” theories of set size, in which Cantor’s Principle (two sets have equally many elements if and only if there is a one-to-one correspondence between them) is abandoned in favor of the Part-Whole Principle (if A is a proper subset of B then A is smaller than B). It has also been suggested that Gödel’s argument for the unique correctness of Cantor’s Principle is inadequate. Here we see from simple examples, not that Euclidean theories of set (...) size are wrong, but that they must be either very weak and narrow or largely arbitrary and misleading. (shrink)

There is recent empirical evidence that personal identity is constituted by one’s moral traits. If true, this poses a problem for those who advocate for moral enhancement, or the manipulation of a person’s moral traits through pharmaceutical or other biological means. Specifically, if moral enhancement manipulates a person’s moral traits, and those moral traits constitute personal identity, then it is possible that moral enhancement could alter a person’s identity. I go a step further and argue that under the right conditions, (...) moral enhancement can constitute murder. I then argue that these conditions are not remote. (shrink)

There is no uniquely standard concept of an effectively decidable set of real numbers or real n-tuples. Here we consider three notions: decidability up to measure zero [M.W. Parker, Undecidability in Rn: Riddled basins, the KAM tori, and the stability of the solar system, Phil. Sci. 70(2) (2003) 359–382], which we abbreviate d.m.z.; recursive approximability [or r.a.; K.-I. Ko, Complexity Theory of Real Functions, Birkhäuser, Boston, 1991]; and decidability ignoring boundaries [d.i.b.; W.C. Myrvold, The decision problem for entanglement, in: (...) R.S. Cohen et al. (Eds.), Potentiality, Entanglement, and Passion-at-a-Distance: Quantum Mechanical Studies fo Abner Shimony, Vol. 2, Kluwer Academic Publishers, Great Britain, 1997, pp. 177–190]. Unlike some others in the literature, these notions apply not only to certain nice sets, but to general sets in Rn and other appropriate spaces. We consider some motivations for these concepts and the logical relations between them. It has been argued that d.m.z. is especially appropriate for physical applications, and on Rn with the standard measure, it is strictly stronger than r.a. [M.W. Parker, Undecidability in Rn: Riddled basins, the KAM tori, and the stability of the solar system, Phil. Sci. 70(2) (2003) 359–382]. Here we show that this is the only implication that holds among our three decidabilities in that setting. Under arbitrary measures, even this implication fails. Yet for intervals of non-zero length, and more generally, convex sets of non-zero measure, the three concepts are equivalent. (shrink)

In this paper, we explore numerical methods for simulating scalar field con-figurations in non-commutative two-dimensional spaces. We focus on the finite difference techniques employed to compute mixed partial derivatives and the action functional in the presence of non-commutative corrections. The methods presented address the challenges posed by non-commutative geometry, specifically in computing the mixed derivative terms that arise due to the deformation of spatial coordinates. We introduce semi-implicit time-stepping schemes to en-sure numerical stability when dealing with stiff nonlinear terms. The (...) approaches discussed here provide a framework for simulating and analyzing physical systems influenced by non-commutativity, which are not extensively documented in existing literature. (shrink)

Newton published his deduction of universal gravity in Principia (first ed., 1687). To establish the universality (the particle-to-particle nature) of gravity, Newton must establish the additivity of mass. I call ‘additivity’ the property a body's quantity of matter has just in case, if gravitational force is proportional to that quantity, the force can be taken to be the sum of forces proportional to each particle's quantity of matter. Newton's argument for additivity is obscure. I analyze and assess manuscript versions of (...) Newton's initial argument within his initial deduction, dating from early 1685. Newton's strategy depends on distinguishing two quantities of matter, which I call ‘active’ and ‘passive’, by how they are measured. These measurement procedures frame conditions on the additivity of each quantity so measured. While Newton has direct evidence for the additivity of passive quantity of matter, he does not for that of the active quantity. Instead, he tries to infer the latter from the former via conceptual analyses of the third law of motion grounded largely on analogies to magnetic attractions. The conditions needed to establish passive additivity frustrate Newton's attempted inference to active additivity. (shrink)

This paper explores the mathematical details behind the geometric transformation of folding a circle into a cone. It includes detailed theo- rems, proofs, and Python implementations for visualization, providing a thorough analysis of the transformation process.

In this paper, we define and explore the mathematical space S, a system where traditional numerical elements like natural numbers are undefined due to the non-evaluability of certain integrals. We investigate how purely formal and logical structures can be constructed within S without numerical interpretations, and we explore how the concept of infinity can be approached within this framework. The document also includes discussions on the implications, applications, and potential future explorations within S.

In this paper, we explore the properties and optimization techniques related to polyhedral cones and energy numbers with a focus on the cone of positive semidefinite matrices and efficient computation strategies for kernels. In Part (a), we examine the polyhedral nature of the cone of positive semidefinite matrices, , establishing that it does not form a polyhedral cone for due to its infinite dimensional characteristics. In Part (b), we present an algorithm for efficiently computing the kernel function on-the-fly, leveraging a (...) polyhedral description of the convex hull generated by the feature mappings and . By restructuring the problem and using gradient-based optimization techniques, our approach minimizes memory usage and computational overhead, thus enabling scalable computation. Through examples and visualizations, we demonstrate the practical applications and efficiency of the proposed algorithm in optimizing these kernel computations. (shrink)

We present a formal mechanical analysis using sweeping net methods to approximate surfacing singularities of saddle maps. By constructing densified sweeping subnets for individual vertices and integrating them, we create a comprehensive approximation of singularities. This approach utilizes geometric concepts, analytical methods, and theorems that demonstrate the robustness and stability of the nets under perturbations. Through detailed proofs and visualizations, we provide a new perspective on singularities and their approximations in analytic geometry.

Spinor theory and its applications are indispensable in many areas of theoretical physics, especially in quantum mechanics, general relativity, and string theory. Spinors are complex objects that transform under specific representations of the Lorentz or rotation groups, capturing the intrinsic spin properties of particles. Recent developments in mathematical abstraction have provided new insights and tools for exploring spinor dynamics, particularly through the lens of motivic operators and M-Posit transforms. This paper delves into the intricate dynamics of spinors subjected to motivic (...) operators and MPosit transforms. Motivic operators encapsulate intrinsic algebraic properties and perturbations, leading to highly evolved spinor states without reliance on external coordinate systems. The M-Posit transform, a novel operator designed for spinors, leverages fractal morphic properties, topological congruence, and quantum-inspired perturbations to manipulate spinor structures within an infinitedimensional oneness geometry calculus. Drawing on the foundations laid by twistor theory, we aim to redefine the evolution of spinors using intrinsic properties derived from phenomenological velocity equations. By interpreting spinors as self-propelled twistors, we offer new perspectives on spinor transformations and dynamics. This intrinsic approach not only simplifies the mathematical treatment but also enhances the physical and geometric interpretation of spinor behaviors. The structure of this paper is organized as follows: We begin with the formal definition and computation of spinor components using motivic operators, highlighting the steps involved in their transformations. Following this, we introduce the M-Posit transform and explore its application to spinors, providing detailed mathematical formulations and examples. We also examine the implications of these transformations in higher-dimensional twistor spaces and non-commutative structures. Finally, we extend our analysis to practical applications in quantum computing, fractal image processing, and quantum field theory. The potential of spinning theory redefined through motivic operators and M-posit transforms offers promising avenues for further research in various domains of theoretical physics and mathematics. This paper sets a foundation for these explorations, emphasizing the importance of intrinsic properties and algebraic dynamics in understanding complex spinor evolutions. (shrink)

For Praising Yahovah, I do publish these mathematical gesturing forms from the infinity meaning of His word. Thanks mom! -/- This quasi-quanta language package outlines methods for combining by topological functor entanglement, symbolic, numeric-energy components. Methods, guidelines and algebraic rules for combining the quasi-quanta into the energy number equivalencies are also notated herein. -/- The Quasi-Quanta Language Package is intended to show the symbolic patterns for configuring the quasi quanta symbology into the numeric energy expressions. This should put to rest (...) any doubt that Energy Numbers are indeed a real, logically configured phenomenon a priori to real or complex numbers, but optionally mappable to the real or complex plane. -/- Pre-numeric energy symbol configurations offer a broad language of pattern detection and logical symbol operation delineated with particular solving methods herein. -/- 'This hopefully provides a new way to looking at the branches of mathematics and their inter-operable analog functions. (shrink)

Humans are morally deficient in a variety of ways. Some of these deficiencies threaten the continued existence of our species. For example, we appear to be incapable of responding to climate change in ways that are likely to prevent the consequent suffering. Some people are morally better than others, but we could all be better. The price of not becoming morally better is that when those events that threaten us occur, we will suffer from them. If we can prevent this (...) suffering from occurring, then we ought to do so. That we ought to make ourselves morally better in order to prevent very bad things from happening justifies, according to some, the development and administration of moral enhancement. I address in this paper the idea that moral enhancement could give rise to moral transhumans, or moral post-persons. Contrary to recent arguments that we shouldn’t engender moral post-persons, I argue that we should. Roughly, the reasons for this conclusion are that we can expect moral post-persons to resemble the morally best of us, our moral exemplars. Since moral exemplars promote their interests by promoting the interests of others (or they promote others’ interests at the expense of their own) we can expect moral post-persons to pursue our interests. Since we should also pursue our own interests, we should bring about moral post-persons. (shrink)

The puzzle of petitionary prayer: if we ask for the best thing, God was already going to do it, and if we ask for something that's not the best, God's not going to grant our request. In this paper, we give a new solution to the puzzle.

Despite the lack of evidence for their effectiveness, the use of physical restraints for patients is widespread. The best ethical justification for restraining patients is that it prevents them from harming themselves. We argue that even if the empirical evidence supported their effectiveness in achieving this aim, their use would nevertheless be unethical, so long as well known exceptions to informed consent fail to apply. Specifically, we argue that ethically justifiable restraint use demands certain necessary and sufficient conditions. These conditions (...) are that the physician obtain informed consent for their application, that their application be medically appropriate, and that restraints be the least liberty-restricting way of achieving the intended benefit. It is a further question whether their application is ever medically appropriate, given the dearth of evidence for their effectiveness. (shrink)

We have now mapped the set of analogies Ai,j to conceptual and mechanical meanings. This allows us to recognize how the Group Algebraic System G decomposes into five smaller subsystems, each of which relate to well-known symbolic systems. Furthermore, by recognizing the algorithmic transformations between these subsystems, we can apply each representing a single component of the Group Algebraic System G, or model how algorithms are used in mathematics, by mapping its meaning onto the corresponding transformation steps between the subsystems. (...) Thus, we have transformed a Group Algebraic System G into five simpler subsystems (namely, symbolic analogic, lateral algebraic, calculus of infinity tensors, perturbations in waves, and algorithmic formation of symbols), each of which may also be represented algorithmically. This mapping process serves as a the basis for studying the algebraic machinery used in mathematics and logic to manipulate symbols, such as the classical logical systems or algebraic systems, using algorithms. (shrink)

Moral bioenhancement is the potential practice of manipulating individuals’ moral behaviors by biological means in order to help resolve pressing moral issues such as climate change and terrorism. This practice has obvious ethical implications, and these implications have been and continue to be discussed in the bioethics literature. What have not been discussed are the epistemological implications of moral bioenhancement. This article details some of these implications of engaging in moral bioenhancement. The argument begins by making the distinction between moral (...) bioenhancement that manipulates the contents of mental states and that which manipulates other, non-representational states. Either way, I argue, the enhanced moral psychology will fail to conform to epistemic norms, and the only way to resolve this failure and allow the moral bioenhancement to be effective in addressing the targeted moral issues is to make the moral bioenhancement covert. (shrink)

The Riemann zeta function ζ(s) is a central object in number theory and complex analysis, defined for complex variables and intimately connected to the distribution of prime numbers through its zeros. The famous Riemann Hypothesis conjectures that all non-trivial zeros of the zeta function lie on the critical line Re(s) = 1 2 . In this paper, we explore the Riemann zeta function through the lens of set-theoretic and sweeping net methods, leveraging creative comparisons of specific sets to gain deeper (...) insight into the distribution of its zeros. By rewording and analyzing the Riemann Hypothesis using set-theoretic arguments, applying sweeping net techniques, and integrating modal logic interpretations, we aim to provide new perspectives and support for this profound conjecture. Our objectives are: • Define the zeta function and its properties relevant to the zeros. • Reword the Riemann Hypothesis using set-theoretic language and establish logical equivalence. • Introduce and compare specific sets related to the zeros of ζ(s). • Apply set-theoretic and sweeping net methods to analyze the distribution of zeros. • Provide rigorous proofs about the absence of zeros in certain regions, including mechanical justifi- cations with all steps. • Incorporate modal logic interpretations into the proof. • Discuss implications for the Riemann Hypothesis. (shrink)

I write this introduction with much work already completed in this 4th Edition of The Cone of Perception, primarily to frame the work and touch on what might be missing from it. Namely → though it is hardly lacking these, I’d like to add a few insights about the content of the work and its relevance to the subject and future technology. Why is this work still relevant? How can you use it in your work/subject/area/field, and how am I supposed (...) to read all of these equations?!! This work is relevant, because is shows us that what we may have thought impossible is phenomenological and actualized. That there are, compressed within simple formulations of geometry and parameters of spatio-temporal experiencing, really a complex harmony of relations, coefficients, hexadecimal coefficients, equilibrium, dynamics, resonances, all of which are alternating with each other in a dance of higher dimensionality through many balancing solutions. All of this, and infinitely more is going on between the distance from me to you, and between each particle in between us. You can use this in your life, work, or area of study, practically no matter what it is that you study, because these equations and insights apply to the fundament of the fabric of reality that we all share and live and the consciousness of it. Whether you are a physicists or a monk, these equations reveal answers and are the answers for the eternal questions of nature and reality. Harmony with number, visual forms, etc. are a new language. Why have questions about God been so hard to express? Words don’t always do justice to the potency of philosophical debate. Much magic mystery and magic have been neglected because of this, but math, equations, visualizations, etc. can do more to reveal insights and converse on topics philosophers have been seeking for ages. Also, this book reveals that what science is currently doing with particle accelerators, while offering its own set of insights, may actually be less productive, wasteful, unnecessary and dangerous that we think. What The Cone of Perception offers is a mental scope that will lead you on a journey from what is currently smaller than what physicists currently believe is the smallest mass/time unit all the way out to numbers and equations so large that they are not allowed by God for us to currently visualize their form. The Cone of Perception has revealed that there are particles of the photo electric effects with mass smaller than the quantum foam. That is a revelation that ought turn the obtuse world of physics on its head. There are many other section in The Cone of Perception all with equally revolutionary material. This work is meant to revolutionize the current perception of the physical world. These equations are useful to those who study dynamics, seek understanding of balance, and those who seek visualizations, mystery and empirical proof of metaphysics and magic in this world. (shrink)

Contemporary scholarship is divided over whether Anselm maintains a version of Eudaemonism. The debate centers on the question of whether the will for justice only moderates the will for happiness or, instead, provides a distinct end for which to act. Because of two key passages, various scholars hold that Anselm maintained elements of medieval Eudaemonism. In this article, I argue that Anselm separates morality from happiness, and I provide a sketch of his alternative view. First, I argue against some recent (...) perspectives that Anselm maintained Eudaemonism. To do so, I provide a non-Eudaemonist reading of the two key passages and show how Eudaemonist readings are lacking in different respects. Second, I examine what this argument means for Anselm’s understanding of happiness and moral obligation. While there are some Eudaemonist themes in Anselm’s thinking, he flatly denies and revises aspects of the system. (shrink)

With essay deadlines looming for many of our students, Matt Parker relives some of the angst involved in writing philosophy. You’re not alone.

As the federal government distributed remdesivir to some of the states COVID-19 hit hardest, policymakers scrambled to develop criteria to allocate the drug to their hospitals. Our state, Michigan, was among those states to receive an initial quantity of the drug from the U.S. government. The disparities in burden of disease in Michigan are striking. Detroit has a death rate more than three times the state average. Our recommendation to the state was that it should prioritize the communities that bear (...) a disproportionate burden of suffering in the allocation of the new potential treatment. This recommendation is justified not only for new drugs with uncertain effects, but also for drugs of certain benefit or vaccines. For states with significant health disparities, such as Michigan, this allocation priority may help to repair them. In fact, any other allocation strategy may make them worse. (shrink)

If you have enjoyed any of the 7 (seven) other books I have published over 20 years, including literally thousands of pages of mathematical and topological concepts, Python programs and conceptually expanding papers, please consider buying this book for $20.00 on google play books. -/- Introduction: -/- Though the following pages provide extensive exposition and dedicated descriptions of the phenomenological velocity formulas, theory and mystery, I thought it appropriate to write this introduction as a partial explanation for what phenomenal velocity (...) is, and describe, briefly its theory and applications. Phenomenological Velocity is a method for solving for something that ought cancel out with itself, but there are specific implicit forms for this thing that, “ought cancel out with itself,” namely the Lorentz coefficient ought cancel out with itself when applied to the height of a cone derived from the difference between the circumferences of two circles applied to the Pythagorean Theorem, or, more generally, the height implied by application of the Pythagorean theorem to the difference between two arc lengths’ equaling a third arc length. These difference equations are essential to conceptualizing differentiation, and in these further chapters, I demonstrate that the phenomenological velocity is, indeed the conditional derivative in the chapter, “Conditional Integral of Phenomenological Velocity.” The phenomenological velocity algebraic solution to the velocity within the Lorentz coefficient when applied to the height function in such a way that it ought cancel out with itself is both constructive mathematics and it employs the concept of, “bracketing,” - first introduced by Edmund Husserl in his writings on the phenomenological reduction. Phenomenological Velocity’s algebraic solution from the difference between two arc lengths applied to the Pythagorean Theorem to solve for a theoretical height (which is a projected distance in space), employs bracketing, because we, “set aside,” the existence of an undefined solution, namely due to the presence of necessitated complex analytical forms by the architecture of the equation, or the “mathetecture,” of the algebraic form. -/- With respect to theology, the phenomenological velocity is somehow symbolic of the creation itself; symbolic of creation due to the fact that we find the canceling out of the Lorentz coefficient as, “impotent,” non-existent or non-effecting to the mathetecture of the height function. However, via the modus-ponens work around to phenomenological velocity, which in itself does not require the complex field, but embeds implied complex field solutions to the equation while maintaining logical consistency, we find existence from non-existence. This is directly linguistically applicable to the concept of the big-bang, the resurrection of Yeshua the Messiah, and opens analogies for us to draw relationships between the, “fall,” of Adam and Eve as the generation of error, or the introduction of paradox, as we see the phallus representing paradox topologically. -/- The phenomenological velocity is a gestalt concept, relevant to cosmology, because we find that it is the perfect language-form for discussing dark matter. It does, however, require the reader to re-conceive or re-frame rather, some of the fundamental aspects of assumed physical reality like time, experience, solidity of dark matter, etc. We find the hidden dimension of phenomenological velocity to have been an overlooked aspect of mathematical physics by the researchers of Bell’s theorem and undoubtedly a host of other theorems. Thus, raising awareness about the real existence and necessitated reality of phenomenological velocity is in no way an endeavor deserving further procrastination by the scientific community, for doing so would be intellectually dishonest and further the propagation of incomplete or misleading theories on reality. -/- This work details how the Lorentz coefficient, when applied to the height of a cone in such a way as to cancel out with itself, permits the velocity variable to have a solution to it anyway, even though it ought cancel out with itself. This mathe-tecture, so to speak has consequences for complex analysis, and pave the way for, "transcendental relativity," building an adaptive framework for consciousness and physical reality. (shrink)

Default positions, predetermined starting points that aid in complex decision-making, are common in clinical medicine. In this article, we identify and critically examine common default positions in clinical ethics practice. Whether default positions ought to be held is an important normative question, but here we are primarily interested in the descriptive, rather than normative, properties of default positions. We argue that default positions in clinical ethics function to protect and promote important values in medicine—respect for persons, utility, and justice. Further, (...) default positions in clinical ethics may also guard against harm. Where default positions exist, there are epistemic burdens to overturn them. The person wishing to reject the default position, rather than the person endorsing it, bears this burden. The person who bears the burden of meeting the epistemic requirements must provide evidence proportional to the degree of harm the default position protects against. Default positions that protect against significant harm impose significant epistemic requirements to overturn. This asymmetry not only makes medical decision-making more economical but also serves to promote and protect certain values. The identification and analysis of common and recognizable default positions can help to identify other default positions and the conditions under which their associated epistemic requirements are met. The article concludes with considerations of potential problems with the use of default positions in clinical ethics. (shrink)

Recently a number of scientists have proposed substantial changes to the practice of climate modeling, though they disagree over what those changes should be. We provide an overview and critical examination of three leading proposals: the unified approach, the hierarchy approach and the pluralist approach. The unified approach calls for an accelerated development of high-resolution models within a seamless prediction framework. The hierarchy approach calls for more attention to the development and systematic study of hierarchies of related models, with the (...) aim of advancing understanding. The pluralist approach calls for greater diversity in modeling efforts, including, on some of its variants, more attention to empirical modeling. After identifying some of the scientific and institutional challenges faced by these proposals, we consider their expected gains and costs, relative to a business-as-usual modeling scenario.We find the proposals to be complementary, having valuable synergies. But since resource limitations make it unlikely that all three will be pursued, we offer some reflections on more limited changes in climate modeling that seem well within reach and that can be expected to yield substantial benefits. (shrink)

We present a novel approach to defining the mathematical constant π through the infinite den- sification of a sweeping net, which approximates a circle as the net becomes infinitely dense. By developing and enhancing notation related to sweeping nets and saddle maps, we establish a rigor- ous framework for expressing π in terms of the densification process using reverse integration. This method, inspired by the concept that numbers ”come from infinity,” leverages a reverse integral approach to model the transition from (...) infinite densification to the finite circle. Our work not only offers a new perspective on the geometric interpretation of π but also provides insights into reverse integration techniques and their applications in mathematical analysis. (shrink)

Published with great thanksgiving for Yaohushua, the living One Yahowah, "Jesus Christ." -/- In previous work, Formalizing Mechanical Analysis Using Sweeping Net Methods I, sweeping net methods have been extended to complex analysis, relying on the argument of complex functions defined on the unit circle. In this paper, we reformulate these methods purely within a real-valued and geometric framework, avoiding the use of complex analysis. By redefining the sweeping net constructs and the associated theorems using real functions and geometric interpretations (...) on the unit circle, we demonstrate how singularities and their approximations can be effectively analyzed without the need for imaginary numbers. This approach provides intuitive geometric insights and broadens the applicability of sweeping net methods in mathematical analysis. (shrink)

Most current dental ethics curricula use a deontological approach to biomedical and dental ethics that emphasizes adherence to duties and principles as properties that determine whether an act is ethical. But the actual ethical orientation of students is typically unknown. The purpose of the current study was to determine the ethical orientation of dental students in resolving clinical ethical dilemmas. First-year students from one school were invited to participate in an electronic survey that included eight vignettes featuring ethical conflicts common (...) to the health care setting. The Multidimensional Ethics Scale was used to evaluate the students’ ethical judgments of these conflicts. Students rated each vignette along 13 ethically relevant items using a 7-point scale. Nine of the thirteen items were analyzed because they represent the dominant ethical theories, including deontology. One hundred sixteen dental students successfully completed the survey. Of the analyzed items, those associated with deontology had comparatively weak associations with whether students judged the action to be ethical and whether students judged themselves likely to perform the action. Whether an action was judged to be caring had the strongest association with whether the action was judged to be ethical and whether students judged themselves likely to perform the action. These results suggest that adherence to duties or principles has weaker association with students’ ethical judgments and behavior compared to caring, which was found to be more influential in their ethical judgments and behavior. Current dental school curricula with a primary focus on deontology may no. (shrink)

Description In this paper, we propose an advanced mathematical framework centered around the Energy Number Field (E), which fundamentally avoids the conventional concept of zero by introducing a neutral ele- ment, νE. Through this approach, we redefine core mathematical constructs, including limits, continuity, differentiation, integration, and series summation, ensuring they operate seamlessly within a zero-less paradigm. We address and redefine matrix operations, topology, metric spaces, and complex analysis, aligning them with the principles of E. Additionally, we explore non-mappable properties of (...) energy numbers in the context of symmetry groups, non-standard fields, fractional calculus, and non-Euclidean geometries. By employing νE as the central element, our framework resolves conventional zero-related sin- gularities and computational anomalies, offering a novel perspective that bridges advanced mathematical theories with practical applications in physics, computational algorithms, and topological transforma- tions. This work paves the way for future research to experimentally validate these formulations and explore potential applications in advanced physics, quantum mechanics, and beyond. (shrink)

We aim to establish the following claim: other factors held constant, the relative weights of the epistemic burdens of competing treatment options serve to determine the options that patient surrogates pursue. Simply put, surrogates confront an incentive, ceteris paribus, to pursue treatment options with respect to which their knowledge is most adequate to the requirements of the case. Regardless of what the patient would choose, options that require more knowledge than the surrogate possesses (or is likely to learn) will either (...) be neglected altogether or deeply discounted in the surrogate’s incentive structure. We establish this claim by arguing that the relation between epistemic burdens and incentives in decision-making is a general feature of surrogate decision-making. After establishing the claim, we draw out some of the implications for surrogate decision-making in medicine and offer philosophical and psychological explanations of the phenomenon. (shrink)

As the science and technology of the brain and mind develop, so do the ways in which brains and minds may be surveilled and manipulated. Some cognitive libertarians worry that these developments undermine cognitive liberty, or “freedom of thought.” I argue that protecting an individual’s cognitive liberty undermines others’ ability to use their own cognitive liberty. Given that the threatening devices and processes are not relevantly different from ordinary and frequent intrusions upon one’s brain and mind, strong protections of cognitive (...) liberty may proscribe neurotechnological intrusions, but also ordinary intrusions. Thus, the cognitive libertarian position “hog-ties” others’ use of their own liberties. This problem for the cognitive libertarian is the same problem that ordinary libertarianism faces in protecting individual rights to property and person. But the libertarian strategies for resolving the problem don’t work for the cognitive libertarian. I conclude that the right to mental privacy is weaker than what cognitive libertarians want it to be. (shrink)

It has recently been argued that a person’s moral judgments (about both their own and others’ actions) are constrained by the nature and extent of their relevant ignorance and, thus, that such judgments are determined in the first instance by the person’s epistemic circumstances. It has been argued, in other words, that the epistemic is logically prior to other normative (e.g., ethical, prudential, pecuniary) considerations in human decision-making, that these other normative considerations figure in decision-making only after (logically and temporally) (...) relevant ignorance has constrained the decision-maker’s menu of options. If this is right, then a person’s moral judgments in some set of circumstances should vary with their knowledge and ignorance of these circumstances. In this study, we test the hypothesis of the logical priority of the epistemic. We describe two experiments in which subjects’ knowledge and ignorance of relevant consequences were manipulated. In the second experiment, we also compared the effect of ignorance on moral judgments with that of personal force, a factor previously shown to influence moral judgments. We found broad empirical support for the armchair arguments that epistemic considerations are logically prior to normative considerations. (shrink)

Berger (forthcoming) states that moral intimacy is important in applying the best interests standard. But what he calls moral intimacy requires that someone has overcome epistemic burdens needed to represent the patient. We argue elsewhere that good surrogate decision-making is first and foremost a matter of overcoming epistemic burdens, or those obstacles that stand in the way of a surrogate decision-maker knowing what a patient wants and how to satisfy those preferences. Berger’s notion of moral intimacy depends on epistemic intimacy: (...) the fact that a surrogate's epistemic burdens with respect to the best interests of the incapacitated patient have been adequately surmounted, plus some other feature. Thus, where a particular patient-surrogate relationship fails to be morally intimate, what is lacking is either epistemic intimacy or this second feature. Furthermore, Berger uses the notion of moral intimacy as an explanans for the application of the best interests standard. We argue that the notions of epistemic intimacy and epistemic burdens not only help to explain the notion of moral intimacy, but also better explain the application of the best interests standard. Given the role of epistemic burdens and the epistemic intimacy that overcoming them enables, bioethicists and physicians should consider a surrogate’s epistemic standing relative to the patient’s best interests before pronouncing on the former’s ethical probity. (shrink)

Healthcare systems need to consider not only how to prevent error, but how to respond to errors when they occur. In the United Kingdom’s National Health Service, one strand of this latter response is the ‘No Blame Culture’, which draws attention from individuals and towards systems in the process of understanding an error. Defences of the No Blame Culture typically fail to distinguish between blaming someone and holding them responsible. This article argues for a ‘responsibility culture’, where healthcare professionals are (...) held responsible in cases of foreseeable and avoidable errors. We demonstrate how healthcare professionals can justifiably be held responsible for their errors even though they work in challenging circumstances. We then review the idea of ‘responsibility without blame’, applying this to cases of error in healthcare. Sensitive to the undesirable effects of blaming healthcare professionals and to the moral significance of holding individuals accountable, we argue that a responsibility culture has significant advantages over a No Blame Culture due to its capacity to enhance patient safety and support medical professionals in learning from their mistakes, while also recognising and validating the legitimate sense of responsibility that many medical professionals feel following avoidable error, and motivating medical professionals to report errors. (shrink)

In standard probability theory, probability zero is not the same as impossibility. But many have suggested that only impossible events should have probability zero. This can be arranged if we allow infinitesimal probabilities, but infinitesimals do not solve all of the problems. We will see that regular probabilities are not invariant over rigid transformations, even for simple, bounded, countable, constructive, and disjoint sets. Hence, regular chances cannot be determined by space-time invariant physical laws, and regular credences cannot satisfy seemingly reasonable (...) symmetry principles. Moreover, the examples here are immune to the objections against Williamson’s infinite coin flips. (shrink)

Brummett and Salter propose a useful and timely taxonomy of clinical ethics expertise (2019). As the field becomes further “professionalized” this taxonomy is important, and the core of it is right. It needs some refinement around the edges, however. In their conclusion, Brummett and Salter rightly point out that there is a significant difference between the ethicist whose recommendations are procedure- and process-heavy, consensus-driven, and dialogical and the authoritarian ethicist whose recommendations flow from “private moral views” (Brummett and Salter, 2019). (...) This admission doesn’t go far enough. Brummett and Salter’s taxonomy fails to capture the notion that offering recommendations whose normative force is moral is different in kind from recommendations whose normative force is non-moral, such as those recommendations that are free of moral content or justified by convention. The difference is in kind, not scale. I argue further that clinical ethics expertise, if possible, consists at least in offering recommendations whose normative force is moral. These two claims imply that the taxonomy fails to cut clinical ethics expertise at the joints: the ethicist who offers justified non-moral normative recommendations is a different kind of ethicist from the one who offers justified moral normative recommendations, yet both are categorized as clinical ethics experts. I finish by offering a refinement of the taxonomy that more precisely categorizes clinical ethicists. (shrink)

Schopenhauer’s pessimistic philosophy is a depressing read. He writes many pages about how suffering is the norm, and any happiness we feel is merely a temporary alleviation of suffering. Even so, his account of suffering rings true to many readers. What are we to do with our lives if Schopenhauer is right, and we are doomed to suffer? In this paper, I use William James’ pragmatic method to find practical implications of Schopenhauer’s pessimism. I provide a model for how we (...) are to live our lives in a suffering world, a model that provides means to reduce suffering. (shrink)

We investigate the topological properties of scalar field configurations influenced by non-commutative geometry and time-dependent perturbations. Specifically, we analyze the connectedness of level sets of scalar fields, compute the fractal dimensions of generated patterns, and study the impact of varying non-commutative parameters. Utilizing numerical simulations, we provide evidence of topological bifurcations induced by non-commutative corrections. The analysis is framed within point set topology, and the results are formalized using the theorem-proof structure.

In a recent issue of Bioethics, I argued that compulsory moral bioenhancement should be administered covertly. Alexander Zambrano has criticized this argument on two fronts. First, contrary to my claim, Zambrano claims that the prevention of ultimate harm by covert moral bioenhancement fails to meet conditions for permissible liberty‐restricting public health interventions. Second, contrary to my claim, Zambrano claims that covert moral bioenhancement undermines autonomy to a greater degree than does overt moral bioenhancement. In this paper, I rebut both of (...) these arguments, then finish by noting important avenues of research that Zambrano’s arguments motivate. (shrink)

In biomedical ethics, there is widespread acceptance of moral realism, the view that moral claims express a proposition and that at least some of these propositions are true. Biomedical ethics is also in the business of attributing moral obligations, such as “S should do X.” The problem, as we argue, is that against the background of moral realism, most of these attributions are erroneous or inaccurate. The typical obligation attribution issued by a biomedical ethicist fails to truly capture the person's (...) actual obligations. We offer a novel argument for rife error in obligation attribution. The argument starts with the idea of an epistemic burden. Epistemic burdens are all of those epistemic obstacles one must surmount in order to achieve some aim. Epistemic burdens shape decision-making such that given two otherwise equal options, a person will choose the option that has the lesser of epistemic burdens. Epistemic burdens determine one's potential obligations and, conversely, their non-obligations. The problem for biomedical ethics is that ethicists have little to no access to others' epistemic burdens. Given this lack of access and the fact that epistemic burdens determine potential obligations, biomedical ethicists often can only attribute accurate obligations out of luck. This suggests that the practice of attributing obligations in biomedical ethics is rife with error. To resolve this widespread error, we argue that this practice should be abolished from the discourse of biomedical ethics. (shrink)

Abstract: The intent of this paper is to provide a simple focus on that math- ematical concept and solution, phenomenological velocity to shine light on a worthy topic for mathematicians and physicists alike. Phenomenological Veloc- ity is essential to the formulation of a gestalt cosmology. The bibliography of this paper provides references to the extensive research that has been conducted by myself on the topic. I have performed conditional integrals of the phenomeno- logical velocity in its most liberated standard-algebraic form, (...) I have shown that the computational-phenomenological velocity satisfies its real-analytic solution when not using the speed of light in scientific notation to get the computational version, thus demonstrating that it is a valid solution. So, phenomenological velocity has profound consequences to the foundations of physics as civilization moves into a galactic scale and information is communicated at the quantum level, because it is such a mathematical reality it ought not be ignored when considering topics from hidden dimensions (a real, algebraic technique) and rel- ativity to gravity and dark matter. It gives us a new perspective on how we perceive the meaning of velocity itself with pragnanz, and thus with the new meaning, perspectives can change. I hope the reader will investigate the com- bined research I have performed on this topic, available by referencing the works in this bibliography to fully understand the nature of the arguments being made within. So, this points the right direction for future research, perhaps even with intent to encourage experimental design. (shrink)

We apply the analysis that we have developed over the course of several publications on the significance of ignorance for decision-making, especially in surrogate (and, thus, in political) contexts, to political decision-making, such as it has been, during the COVID-19 pandemic (see Scheall 2019; Crutchfield and Scheall 2019; Scheall and Crutchfield 2020; Scheall 2020). Policy responses to the coronavirus constitute a case study of the problem of policymaker ignorance. We argue that political responses to the virus cannot be explained by (...) assuming that the interests of policymakers were at loggerheads with those of their constituents at the beginning of the crisis. In order to explain the responses of policymakers, it is necessary to recognize the effects of relevant ignorance on their incentives to pursue different policy objectives. We discuss the knowledge that policymakers required at the start of the pandemic in order to deliberately realize the goal of limiting overall human suffering and the spontaneous forces that could have facilitated the realization of this goal. The problem of policymaker ignorance implies that policymakers have not earnestly pursued the goal of limiting overall suffering due to the novel coronavirus, but have repeatedly resorted to the pursuit of relatively less epistemically burdensome goals. The problem of policymaker ignorance explains why policymakers have focused primarily on limiting one kind of suffering – physical suffering due to the virus – and have mostly ignored related kinds of suffering, i.e., the economic, sociological, psychological, and physical suffering caused by policies to limit physical suffering from the virus. The problem of policymaker ignorance also helps to explain why policymakers relied on the relatively blunt instrument of economic lockdown rather than more focused protection policies, and why they continue to resort to lockdowns, despite the emerging scientific evidence of their ineffectiveness at mitigating physical suffering due to the virus. (shrink)